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Sample records for anti cd-20 c2b8

  1. Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

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    Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

    2005-07-01

    Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

  2. High-dose radioimmunotherapy in refractory b-celI non-Hodgikin's lymphoma with I-131-labeled chimeric anti CD-20 C2B8 (I-131 rituximab): pilot trial

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    Kim, Sung Eun; Park, Yeon Hee; Cheon, Gi Jeong; Ryoo, Baek Yeol; Lee, Seung Sook; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of)

    2004-07-01

    The native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed or refractory NHL. This ongoing pilot study was to evaluate whether high-dose radioimmunotherapy (RIT) with I-131 rituximab is therapeutically effective in refractory B-cell NHL. 5 patients (5 male, aged 50.89{+-}16.89) with chemorefractory NHL of B-cell origin (2 diffuse large B cell, 1 burkitt's lymphoma, and 2 mantle cell Iymphoma) oe, with a life expectancy of at least 3 months, and with a Kamofsky performance score of 60 and above were studied. The chimeric IgG1 anti CD 20 monoclonal antibody rituximab (mabthera, Roche) was radiolabelled with iodine-131 (I-131) using a modified chloaramine T method with high radiochemical purity (95%{+-}0.9) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabelled rituximab (18.5 MBq/kg) immediately prior to administration of therapeutic dose (3.7 GBq-8.5 GBq), and then underwent gamma camera scan and pre-and post-RIT FDG PET (within 7 day and day 30). Blood cell nadirs were reached at 2-3 weeks after therapy infusion, but all patients recovered at 6 weeks after treatment. Non hematologic toxicity was restricted to mild-to moderate nausea, fever, transient bilirubin, or liver enzyme elevation. Two (8.5 GBq) with mantle cell lymphoma and one with burkitt's lymphoma experienced good partial remissions, and one (5.5 GBq, DLBL) with bulky disease had a partial remission, and one patient (3.7 GBq, DLBL) with bulky disease had a mixed response. High-dose RIT with I-131 labelled rituximab seems to be effective and moderate toxicity. Further follow-up to monitor the long-term outcome are indicated.

  3. Biodistribution and kinetics of {sup 131}I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma

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    Scheidhauer, Klemens; Wolf, Ingo; Baumgartl, Hans-Joachim; Reidel, Guenther; Schwaiger, Markus [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Muenchen (Germany); Schilling, Christoph von; Schmidt, Burkhard; Peschel, Christian [III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet Muenchen (Germany)

    2002-10-01

    The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq {sup 131}I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that {sup 131}I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with {sup 131}I-labelled rituximab. The therapeutic activities of {sup 131}I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart. (orig.)

  4. Production of an active anti-CD20-hIL-2 immunocytokine in Nicotiana benthamiana.

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    Marusic, Carla; Novelli, Flavia; Salzano, Anna M; Scaloni, Andrea; Benvenuto, Eugenio; Pioli, Claudio; Donini, Marcello

    2016-01-01

    Anti-CD20 murine or chimeric antibodies (Abs) have been used to treat non-Hodgkin lymphomas (NHLs) and other diseases characterized by overactive or dysfunctional B cells. Anti-CD20 Abs demonstrated to be effective in inducing regression of B-cell lymphomas, although in many cases patients relapse following treatment. A promising approach to improve the outcome of mAb therapy is the use of anti-CD20 antibodies to deliver cytokines to the tumour microenvironment. In particular, IL-2-based immunocytokines have shown enhanced antitumour activity in several preclinical studies. Here, we report on the engineering of an anti-CD20-human interleukin-2 (hIL-2) immunocytokine (2B8-Fc-hIL2) based on the C2B8 mAb (Rituximab) and the resulting ectopic expression in Nicotiana benthamiana. The scFv-Fc-engineered immunocytokine is fully assembled in plants with minor degradation products as assessed by SDS-PAGE and gel filtration. Purification yields using protein-A affinity chromatography were in the range of 15-20 mg/kg of fresh leaf weight (FW). Glycopeptide analysis confirmed the presence of a highly homogeneous plant-type glycosylation. 2B8-Fc-hIL2 and the cognate 2B8-Fc antibody, devoid of hIL-2, were assayed by flow cytometry on Daudi cells revealing a CD20 binding activity comparable to that of Rituximab and were effective in eliciting antibody-dependent cell-mediated cytotoxicity of human PBMC versus Daudi cells, demonstrating their functional integrity. In 2B8-Fc-hIL2, IL-2 accessibility and biological activity were verified by flow cytometry and cell proliferation assay. To our knowledge, this is the first example of a recombinant immunocytokine based on the therapeutic Rituximab antibody scaffold, whose expression in plants may be a valuable tool for NHLs treatment.

  5. Microenvironment and anti-CD20 based therapies in CLL

    NARCIS (Netherlands)

    Jak, M.

    2012-01-01

    Chronische lymfatische leukemie (CLL) kenmerkt zich door een ophoping van kwaadaardige B-lymfocyten (witte bloedcellen) in bloed, lymfeklieren, milt en beenmerg. Het is niet te genezen omdat CLL-cellen resistent worden tegen behandeling. Margot Jak onderzocht twee typen anti-CD20-antilichamen. Antil

  6. Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti-CD20 antibody (Rituximab

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    V. Bruzzese

    2011-06-01

    Full Text Available Rituximab is a chemeric murine/human anti-B lymphocyte antigen CD20 monoclonal antibody used in the treatment of rheumatoid arthritis resistant to treatment by one or more anti TNF-alpha therapies (1. The recommended dose for an efficient depletion of the B CD 20 lymphocytes in rheumatoid arthritis is two infusions of 1000 mg, with the second infusion being administered two weeks after the first. At this dose, one obtains a rapid and persistent depletion of CD 20 cells, with repopulation occurring, on the average, in about eight months (2. Here, we present a case of a woman treated with only 50 mg of rituximab, who underwent both a rapid and pronounced reduction of B CD 20 lymphocytes...

  7. Ofatumumab: a novel monoclonal anti-CD20 antibody

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    Thomas S Lin

    2010-05-01

    Full Text Available Thomas S LinGlaxoSmithKline Oncology R&D, Collegeville, PA, USAAbstract: Ofatumumab, a novel humanized monoclonal anti-CD20 antibody, was recently approved by the FDA for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL. Ofatumumab effectively induces complement-dependent cytotoxicity (CDC in vitro, and recent studies demonstrated that ofatumumab also effectively mediates antibody-dependent cellular cytotoxicity (ADCC. Pharmacokinetic studies indicated that increased exposure to the antibody correlated with improved clinical outcome in CLL. Thus, pharmacogenomics may be important in identifying which patients are more likely to respond to ofatumumab therapy, although such studies have not yet been performed. Patients with the high-affinity FCGR3a 158 V/V polymorphism may be more likely to respond to therapy, if ADCC is the primary in vivo mechanism of action of ofatumumab. Patients with increased expression of the complement defense proteins CD55 and CD59 may be less likely to respond if ofatumumab works in vivo primarily via CDC. Patients with increased metabolism and clearance of ofatumumab may have lower exposure and be less likely to respond clinically. Thus, pharmacogenomics may determine the responsiveness of patients to ofatumumab therapy.Keywords: monoclonal antibody, CD20, CLL, NHL, lymphoma

  8. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

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    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  9. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

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    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  10. Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity

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    Lehmann-Horn, Klaus; Kinzel, Silke; Feldmann, Linda; Radelfahr, Florentine; Hemmer, Bernhard; Traffehn, Sarah; Bernard, Claude C A; Stadelmann, Christine; Brück, Wolfgang; Weber, Martin S

    2014-01-01

    Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase of multiple sclerosis (MS). Throughout the secondary-progressive (SP) course of MS, pathogenic B cells may, however, progressively replicate within the central nervous system (CNS) itself, which is largely inaccessible to systemic anti-CD20 treatment. Utilizing the murine MS model of experimental autoimmune encephalomyelitis, we show that intrathecal (i.t.) administration of anti-CD20 alone very efficiently depletes meningeal B cells from established CNS lesions. In SP-MS patients, adding i.t. administration of anti-CD20 to its systemic use may be a valuable strategy to target pathogenic B-cell function. PMID:25356419

  11. Efficacy of anti-CD20 chi- meric Fab′fragment on pro- liferation of B lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The variable domain of heavy chain (VH) and light chain (VL) genes of anti-CD20 monoclonal antibody HI47 were cloned from anti-CD20 ScFv expression vector pCANBTEcd20 by PCR and ligated into vector pYZF to construct chimeric anti-CD20 Fab¢ fragment expression vector pYZFcd20. Chimeric anti-CD20 Fab¢ fragment was expressed in E. coli 16C9 and purified by protein G affinity chromatography. Competitive inhibition assay showed that anti-CD20 Fab¢ fragment inhibited binding of HI47 to CD20 on the surface of Daudi cells. Results from MTT assay indicated that chimeric anti-CD20 Fab¢ fragment inhibited the proliferation of Daudi cells, IC50 = 69 mg/mL. Affinity of chimeric anti-CD20 Fab¢ fragment was determined, Ka was about 8.9′108 (mol/L)-1.

  12. Efecto de un anticuerpo monoclonal anti CD20 (Rituximab) en trombocitopenia inmune.

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    Untama, José; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.; Del Carpio, Daniel; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.

    2012-01-01

    Objetivo: Describir la respuesta terapéutica con un anticuerpo monoclonal anti CD20 (Rituximab), en pacientes con Trombocitopenia Inmune (PTI). Material y métodos: Estudio retrospectivo, descriptivo y observacional tipo serie de casos. Se revisaron las historias clínicas de pacientes adultos con PTI que recibieron el anticuerpo monoclonal anti CD20 (Rituximab), desde diciembre 2005 hasta diciembre 2010. Se definió respuesta: conteo plaquetario >30 mil, por lo menos duplicar el conteo plaqu...

  13. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

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    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  14. Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

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    Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2012-07-01

    Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

  15. Anti-CD20 monoclonal antibodies as novel treatments for non-Hodgkin's lymphoma

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    White, C.A.; Larocca, A.; Grillo-Lopez, A.J. [IDEC Pharmaceuticals, 3030 Callan Road, San Diego, CA (United States)

    1999-03-01

    Anti-CD20 monoclonal antibodies (MAbs) offer new options for patients with non-Hodgkin's lymphoma, needed because existing therapies have many limitations. The unconjugated, chimeric anti-CD20 antibody, Rituximab (MabThera, Rituxan), has recently been approved in the USA for patients with relapsed or refractory, low-grade or follicular, B-cell non-Hodgkin's lymphoma, and in Europe for therapy of relapsed stage III/IV follicular lymphoma. In the pivotal study of Rituximab, an overall response rate of 50% was achieved with median time to progressionin responders of 13.2 months. Studies are ongoing with the {sup 90}Y-labelled murine anti-CD20 antibody, IDEC-Y2B8. The response rate in a Phase I/II study in low-grade and intermediate-grade patients was 67%. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Anti CD20 (Rituximab therapy in refractory pediatric rheumatic diseases

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    Joel Reis

    2016-01-01

    Full Text Available Objectives: We aim to report the efficacy and safety of rituximab (RTX in patients diagnosed with juvenile systemic lupus erythematosus (JSLE or juvenile idiopathic arthritis (JIA refractory to conventional treatment. Methods: A retrospective review was made of all medical records of patients with JSLE or JIA treated with RTX between January 2009 and January 2015 in the Pediatric Rheumatology Unit of a central hospital. Results: Five patients, 4 with JSLE and 1 with extended oligoarticular JIA, received 10 cycles of RTX (23 infusions. The scheme of RTX frequently used was 750 mg/m2 two weeks apart. The median follow-up time after receiving the first cycle of RTX was 24 months (12 – 70. The four patients with JSLE were female (three caucasian and one black. The patient with JIA was a caucasian male. The median age at diagnosis was 10 years (16 months – 17years. The median evolution time until receiving RTX was 6 years (5 months – 15 years. Refractory class IV lupus nephritis was the most common indication for receiving RTX. Previous treatment to RTX included nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, immunosuppressive drugs and corticosteroids in all patients and anti-TNFα (etanercept in the patient with JIA. It was possible to reduce the mean oral corticosteroid dose after RTX, ranging from 23 mg/day (20-25mg/day before RTX to 11 mg/day (0–20 mg/day at the last evaluation. Disease activity before RTX and at last evaluation also improved. The SLEDAI score, for JSLE, decreased from a median of 15, 5 (11 – 18 to 3 (0 – 6, and the JADAS-27 score, for JIA, also diminished from 40.4 to 3.5. Adverse events occurred in 2 patients, including delayed second dose after the diagnosis of cryptococcosis and respiratory tract infection with concomitant hypogammaglobulinemia needing of immunoglobulin replacement and antibiotic therapy. Conclusions: Rituximab might have a role in the treatment of JSLE and JIA

  17. Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes.

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    Hu, Changyun; Ding, Heyuan; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2013-08-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10-producing CD4 T cells in the small intestine through IL-10- and IL-27-producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for T1D.

  18. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

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    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  19. Comparative studies of antibody anti-CD20 labeled with {sup 188}Re; Estudo comparativo da marcacao do anticorpo anti-CD20 com {sup 188}Re

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    Dias, Carla Roberta de Barros Rodrigues

    2010-07-01

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m ({sup 99m}Tc) and rhenium-188 ({sup 188}Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis ({sup 99m}Tc: T{sub 1/2} = 6 h, {gamma} radiation = 140 keV) and therapy ({sup 188}Re: T{sub 1/2} = 17 h, maximum {beta} energy = 2.12 MeV) and to their availability in the form of {sup 99}Mo/{sup 99}mTc and {sup 188}W/{sup 188}Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with {sup 188}Re using two techniques: the direct labeling method [{sup 188}Re(V)] and the labeling method via the carbonyl nucleus [{sup 188}Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with {sup 188}Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both {sup 99}mTc and {sup 188}Re were employed through 2 different procedures: (1) labeling of intact RTX with {sup 99}mTc(I) and (2) reduced RTX (RTX{sub red}) labeled with {sup 99}mTc(I)/{sup 188}Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method

  20. Anti-CD22/CD20 Bispecific antibody with enhanced trogocytosis for treatment of Lupus.

    Directory of Open Access Journals (Sweden)

    Edmund A Rossi

    Full Text Available The humanized anti-CD22 antibody, epratuzumab, has demonstrated therapeutic activity in clinical trials of lymphoma, leukemia and autoimmune diseases, treating currently over 1500 cases of non-Hodgkin lymphoma, acute lymphoblastic leukemias, Waldenström's macroglobulinemia, Sjögren's syndrome, and systemic lupus erythematosus. Because epratuzumab reduces on average only 35% of circulating B cells in patients, and has minimal antibody-dependent cellular cytotoxicity and negligible complement-dependent cytotoxicity when evaluated in vitro, its therapeutic activity may not result completely from B-cell depletion. We reported recently that epratuzumab mediates Fc/FcR-dependent membrane transfer from B cells to effector cells via trogocytosis, resulting in a substantial reduction of multiple BCR modulators, including CD22, CD19, CD21, and CD79b, as well as key cell adhesion molecules, including CD44, CD62L, and β7 integrin, on the surface of B cells in peripheral blood mononuclear cells obtained from normal donors or SLE patients. Rituximab has clinical activity in lupus, but failed to achieve primary endpoints in a Phase III trial. This is the first study of trogocytosis mediated by bispecific antibodies targeting neighboring cell-surface proteins, CD22, CD20, and CD19, as demonstrated by flow cytometry and immunofluorescence microscopy. We show that, compared to epratuzumab, a bispecific hexavalent antibody comprising epratuzumab and veltuzumab (humanized anti-CD20 mAb exhibits enhanced trogocytosis resulting in major reductions in B-cell surface levels of CD19, CD20, CD21, CD22, CD79b, CD44, CD62L and β7-integrin, and with considerably less immunocompromising B-cell depletion that would result with anti-CD20 mAbs such as veltuzumab or rituximab, given either alone or in combination with epratuzumab. A CD22/CD19 bispecific hexavalent antibody, which exhibited enhanced trogocytosis of some antigens and minimal B-cell depletion, may also be

  1. Preparation and quality control of {sup 166}Ho-DTPA-antiCD20 for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zolghadri, S.; Jalilian, A.R.; Yousefnia, H.; Bahrami-Sumani, A.; Shirvani-Arani, S.; Ghannadi-Maragheh, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (IR). Radiopharmaceutical Research and Development Lab. (RRDL)

    2011-07-01

    In this work, anti-CD20 was successively labeled with beta-particle emitting radionuclide, Ho-166, for ultimate radioimmunotherapy applications. Ho-166 chloride was obtained by thermal neutron flux (1 x 10{sup 13} n cm{sup -2} s{sup -1}) of natural Ho{sub 2}(NO{sub 3}){sub 3} sample, dissolved in acidic media. {sup 166}Ho-holmium chloride (185 MBq) was added to the conjugated antibody after ccDTPA residulation at room temperature. Radiochemical purity of 95% (ITLC) and 98% (HPLC) were obtained for final radioimmunoconjugate (specific activity = 3-3.5 GBq/mg). The final isotonic {sup 166}Ho-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies of Ho-166 chloride and radioimmunoconjugate were performed in wild-type rats to determine the biodistribution. The accumulation of the radiolabeled antibody in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled anti-CD20 immunoconjugates. (orig.)

  2. A new approach to comparing anti-CD20 antibodies: importance of the lipid rafts in their lytic efficiency

    Directory of Open Access Journals (Sweden)

    Mariam Hammadi

    2010-06-01

    Full Text Available Mariam Hammadi, Jacques-Olivier Pers, Christian Berthou, Pierre Youinou, Anne BordronCentre Hospitalier Universitaire EA2216 and IFR148, Université de Bretagne Occidentale and Université Européenne de Bretagne, BP824, 29609 Brest cedex, FranceAbstract: The view that B lymphocytes are pathogenic in diverse pathological settings is supported by the efficacy of B-cell-ablative therapy in lymphoproliferative disorders, autoimmune diseases and graft rejection. Anti-B-cell antibodies (Abs directed against CD20 have therefore been generated, and of these, rituximab was the first anti-CD20 monoclonal Ab (mAb to be applied. Rituximab-mediated apoptosis, complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity differ from one disease to another, and, for the same disease, from one patient to another. This knowledge has prompted the development of new anti-CD20 mAbs in the hope of improving B-cell depletion. The inclusion of CD20/anti-CD20 complexes in large lipid rafts (LRs enhances the results of some, but not all, anti-CD20 mAbs, and it may be possible to include smaller LRs. Lipid contents of membrane may be abnormal in malignant B-cells, and could explain resistance to treatment. The function of these mAbs and the importance of LRs warrant further investigation. A detailed understanding of them will increase results for B-cell depletion in lymphoproliferative diseases.Keywords: anti-CD20 antibodies, lymphocyte B, lipid rafts, B-cell disorders

  3. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    Science.gov (United States)

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  4. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia.

    Science.gov (United States)

    Paganelli, Massimiliano; Patey, Natacha; Bass, Lee M; Alvarez, Fernando

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.

  5. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

    DEFF Research Database (Denmark)

    Da Roit, F.; Engelberts, P. J.; Taylor, R. P.

    2015-01-01

    -treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells...

  6. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  7. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles; Sistema multivalente para terapia de linfomas no-Hodking basado en Anti-CD20 conjugado a nanoparticulas de oro

    Energy Technology Data Exchange (ETDEWEB)

    Miranda O, R. M.

    2014-07-01

    In recent publications has been reported that gold nanoparticles have an effect in reducing the expression of the oncogene Bcl -2 and have a high biocompatibility , this is the importance for using gold nanoparticles for this work. The antibody CD20 is an antibody that specifically binds to that over expressed CD20 antigen on the cell membrane of B lymphoma cell non- Hodgkin (cell line Raji) behold the importance of combining this bio molecule to gold nanoparticles since they have a high specificity with CD20 positive cells , also to carry out the antigen- antibody immunological reactions triggered mediating cell lysis, possibly by cytotoxicity and apoptosis. Therefore, this system must have characteristics of both components to eliminate B cell non- Hodgkin lymphoma.In this work it was studied a multivalent system composed of gold nanoparticles and anti-CD20 antibody, the term multi valency refers to the number of biomolecules attached to the surface of the gold nanoparticle. The synthesis and characterization of the gold nanoparticles and the multivalent system was performed and the effect of the multivalent system on the expression of oncogene Bcl-2 (group of proteins associated with the apoptotic pathway) was evaluated. Characterization of raw materials and the multivalent system was performed using spectroscopic and microscopic techniques, this to verify structural changes in raw materials and thus confirm the formation of CD20 binding to the surface of the nanoparticle gold by the bond between gold and sulfur in the cysteines of CD20. Taking advantage that the metal nanoparticles have the optical property of surface plasmon resonance, the absorption of gold nanoparticles was measured on the UV-Vis as it is affected by the surface molecules bind to it, showing a bathochromic displacement effected. The hydrodynamic diameter of the gold nanoparticles was measured to verify that the antibody is bound to the surface; this evidence was complemented by micrographs

  8. Preparation of the radiopharmaceutical {sup 131}I-Anti-CD20 for the treatment of lymphomas; Preparacion del radiofarmaco {sup 131}I-Anti-CD20 para el tratamiento de linfomas

    Energy Technology Data Exchange (ETDEWEB)

    Pantoja H, I.E

    2004-07-01

    At the present time they are considered to the lymphomas like a problem of first magnitude since has happened it is necessary to be the fifth cancer cause in the world. Different treatments focused to the lymphoma like the chemotherapy and the radiotherapy, have been employees to counteract the No-Hodgkin lymphoma, without these they don't exclude the healthy tissue of the toxicity. It is for it that is taking a new direction with the employment of the directed radioimmunotherapy since this it allows to kill wicked cells selectively with radiation dose joined to the apoptosis and cytotoxicity induced by the own one bio molecule. The radioimmunotherapy with radiolabelled antibodies directed to the surface antigen CD20 represents a new modality for the treatment of No-Hodgkin lymphoma and potentially other illnesses. In this work the parameters of optimization are presented for the preparation, control of quality and evaluation of the stability in vitro and in vivo of the monoclonal antibody anti-CD20 labelled with {sup 131} I for the treatment of No-Hodgkin lymphoma. The anti-CD20 labelled by the chloramine-T method with high radiochemical purity (>98%), it is stable in solution for but of a half life of the radionuclide (8.04 days) The {sup 131} I-anti-CD20 doesn't present dehalogenation in vitro (human serum) during 24 h of incubation at 37 C. According to the tests carried out to establish the immunoreactivity, a percentage of union to cells was obtained (B lymphocytes) bigger to 30%. The biodistribution in mice balb/c one hour after their administration, it shows that there is not high reception in mucous neither kidneys, what indicates that the complex is stable in vivo. In conclusion, the radiopharmaceutical {sup 131} I-anti-CD20 was obtained in sterile injectable solution and free of pyrogens with a radiochemical purity bigger to 98% and a specific activity of 296 MBq. The radiolabelled molecule maintains its biological recognition for the receiving

  9. Binding Activity Difference of Anti-CD20 scFv-Fc Fusion Protein Derived from Variable Domain Exchange

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Beifen Shen; Jiannan Feng; Yan Li; Yingxun Sun; Xin Gu; Ying Huang; Yugang Wang; Xianjiang Kang; Hong Chang

    2006-01-01

    Two novel engineered antibody fragments binding to antigen CD20 were generated by fusing a murine IgM-type anti-CD20 single-chain Fv fragment (scFv) to the human IgG1 CH2 (I.e., Cγ2) and CH3 (I.e., Cγ3) domains with the human IgG1 hinge (I.e. Hγ). Given the relationship between structure and function of protein, the 3-D structures of the two engineered antibody fragments were modeled using computer-aided homology modeling method.Furthermore, the relationship between 3-D conformation and their binding activity was evaluated theoretically.Due to the change of active pocket formed by CDRs, the HL23 (VH-Linker-VL-Hγ-Cγ2-Cγ3) remained its activity because of its preserved conformation, while the binding activity of the LH23 (VL-Linker-VH-Hγ-Cγ2-Cγ3) was impaired severely. Experimental studies by flow cytometry and fluorescence microscopy showed that HL23 possessed significantly superior binding activity to CD20-expressing target cells than LH23. That is to say, the order of variable regions could influence the binding activity of the fusion protein to CD20+ cell lines, which was in accordance with the theoretical results. The study highlights the potential relationship between the antibody binding activity and their 3-D conformation, which appears to be worthwhile in providing direction for future antibody design of recombinant antibody.

  10. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

    Directory of Open Access Journals (Sweden)

    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  11. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies

    Science.gov (United States)

    Grandjean, Capucine L.; Montalvao, Fabricio; Celli, Susanna; Michonneau, David; Breart, Beatrice; Garcia, Zacarias; Perro, Mario; Freytag, Olivier; Gerdes, Christian A.; Bousso, Philippe

    2016-01-01

    Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs. PMID:27698437

  12. The Different Clinical Effects of Anti-BLyS, Anti-APRIL and Anti-CD20 Antibodies Point at a Critical Pathogenic Role of gamma-Herpesvirus Infected B Cells in the Marmoset EAE Model

    NARCIS (Netherlands)

    Jagessar, S. Anwar; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D.; Oh, Luke; Migone, Thi; Verschoor, Ernst J.; 't Hart, Bert A.

    2013-01-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephal

  13. Overcoming rituximab drug-resistance by the genetically engineered anti-CD20-hIFN-α fusion protein: Direct cytotoxicity and synergy with chemotherapy

    Science.gov (United States)

    VEGA, GABRIEL G.; FRANCO-CEA, LUZ ARELI; HUERTA-YEPEZ, SARA; MAYANI, HÉCTOR; MORRISON, SHERIE L.; BONAVIDA, BENJAMIN; VEGA, MARIO I.

    2015-01-01

    Treatment of patients with B-NHL with rituximab and CHOP has resulted in significant clinical responses. However, a subset of patients develops resistance to further treatments. The mechanism of unresponsiveness in vivo is not known. We have reported the development of rituximab-resistant clones derived from B-NHL cell lines as models to investigate the mechanism of resistance. The resistant clones exhibit hyper-activated survival/anti-apoptotic pathways and no longer respond to a combination of rituximab and drugs. Recent studies reported the therapeutic efficacy in mice bearing B-cell lymphoma xenografts following treatment with the anti-CD20-hIFNα fusion protein. We hypothesized that the fusion protein may bypass rituximab resistance and inhibit survival signaling pathways. Treatment of the rituximab-resistant clones with anti-CD20-hIFNα, but not with rituximab, IFNα, or rituximab+IFNα resulted in significant inhibition of cell proliferation and induction of cell death. Treatment with anti-CD20-hIFNα sensitized the cells to apoptosis by CDDP, doxorubicin and Treanda. Treatment with anti-CD20-hIFNα inhibited the NF-κB and p38 MAPK activities and induced the activation of PKC-δ and Stat-1. These effects were corroborated by the use of the inhibitors SB203580 (p38 MAPK) and Rottlerin (PKC-δ). Treatment with SB203580 enhanced the sensitization of the resistant clone by anti-CD20-hIFNα to CDDP apoptosis. In contrast, treatment with Rotterin inhibited significantly the sensitization induced by anti-CD20-hIFNα. Overall, the findings demonstrate that treatment with anti-CD20-hIFNα reverses resistance of B-NHL. These findings suggest the potential application of anti-CD20-hIFNα in combination with drugs in patients unresponsive to rituximab-containing regimens. PMID:26398317

  14. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

    Directory of Open Access Journals (Sweden)

    Capolla S

    2015-06-01

    Full Text Available Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl, Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of Chicago, Chicago, IL, USA; 8Department of Human Pathology, University of Palermo, Palermo, Italy; 9Callerio Foundation Onlus, Institutes of Biological Researches, Trieste, Italy Abstract: The expectations of nanoparticle (NP-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together

  15. Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ghanashyam Sarikonda

    Full Text Available A recent type 1 diabetes (T1D clinical trial of rituximab (a B cell-depleting anti-CD20 antibody achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin with anti-CD3 antibody (a T cell-directed immunomodulator offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks was also ineffective, while proinsulin DNA (weekly for up to 12 weeks showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04. In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.

  16. Dosimetric evaluation of anti-CD20 labelled with {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a {sup 188}W/{sup 188}Re generator system represents an attractive alternative radionuclide for therapy. {sup 188}Re is produced from beta decay of the {sup 188}W parent. In addition to the emission of high-energy electrons (E{beta}= 2118 keV), {sup 188}Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of {sup 188}Re, the emission of gamma photon is an added advantage since the biodistribution of {sup 188}Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  17. Radiolabeling of anti-CD20 with Re-188 for treatment of non-Hodgkin's lymphoma: radiochemical control

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla R.; Osso Junior, Joao A., E-mail: carladias@usp.b, E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The development of tumor-selective radiopharmaceuticals is clinically desirable as a means of detecting or confirming the presence and location of primary and metastatic lesions and monitoring tumor response to (chemo)therapy. In addition, the application of targeted radiotherapeutics provides a unique and effective modality for direct tumor treatment. In this manner the radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. Antibody therapy directed against the CD20 antigen on the surface of B-cells is considered one of the first successful target-specific therapies in oncology. The radionuclide rhenium-188 ({sup 188}Re) is currently produced from the father nuclide tungsten-188 ({sup 188}W) through a transportable generator system. Because of its easy availability and suitable nuclear properties (EbetaMAX = 2.1 MeV, t{sub 1/2} = 16.9 h, Egamma = 155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agent and could be conveniently utilized for imaging and dosimetric purposes. The purpose of this work is to show the radiochemical control of the optimized formulation (solution) and lyophilized formulation (kit) of labeled rituximab (anti-CD20) with {sup 188}Re. Rituximab was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulfhydryl groups was assayed with Ellman's reagent. Radiochemical purity of {sup 188}Re-rituximab was evaluated using instant thin layer chromatography-silica gel (ITLC-SG). Quality control methods for evaluation of radiochemical purity showed good labeling yield of the antibody. (author)

  18. Standardization of methodology to derivatization and radiolabeling of the anti-CD20 monoclonal antibody from bifunctional chelator DOTA-NHS-Ester

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Akanji, Akinkunmi G.; Santos, Josefina S.; Pujatti, Priscilla B.; Couto, Renata M.; Massicano, Felipe; Araujo, Elaine Bortoleti de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], E-mail: adriana.avfernandes@gmail.com

    2009-07-01

    Lymphomas are cancers of the lymphatic system, being the most common the non-Hodgkin lymphoma (NHL). The Radioimmunotherapy (RIT), that increase the cytotoxic effect of monoclonal antibodies (mAb), therefore labeling these Mab with different radioisotopes. RIT combines the specificity of the antibody and the toxicity of the radionuclides. The mAb anti-CD20 is used for treatment of relapse or refractory NHL. The labeling of anti- CD20 with {sup 177}Lu, requires a bifunctional chelating agent that is designed to make a 'connect bridge' between the mAb and the radionuclide. The incorporation of the chelating group in mAb structure is called derivatization. The aim of this work is to study the derivatization of anti-CD20 antibody with DOTA-NHS-ester chelating group and labeling parameters to produce {sup 177}Lu-DOTA-Anti CD20. Five milligrams of anti-CD20 were purified by dialysis against phosphate buffer pH 8.0 and derivatized with DOTA-NHS-ester in 1:250, 1:500 and 1:1000 molar ratios. The reaction was conducted for 1 hour in gently mixing at room temperature and remained under refrigeration for 48 hours. The reaction mixture was purified in gel column Sephadex G-50 ; the aliquots that presented greater protein concentration, were mixed and concentrated. The purified antibody conjugated was added to 111-185MBq (3-5mCi) of {sup 177}LuCl3 diluted in 0.4 M acetate buffer pH 5.5. Radiochemical purity was less than 95% in all the molar ratios, indicating necessity of the purification after the labeling. The mAb derivatized showed stable when stored for to 1 month to 4 deg C and 4 days at -20 deg C. (author)

  19. Human IgG1 Cγ1 Domain Is Crucial for the Bioactivity of the Engineered Anti-CD20 Antibodies

    Institute of Scientific and Technical Information of China (English)

    Shusheng Geng; Jiannan Feng; Yan Li; Xianjiang Kang; Yingxun Sun; Xin Gu; Ying Huang; Hong Chang; Beifen Shen

    2007-01-01

    In this study, we discussed the necessity of human IgG1 Cγ1 domain for recombinant antibody using computeraided homology modeling method and experimental studies. The heavy (VH) and light (VL) chain variable regions of 1-28, a murine IgM-type anti-CD20 mAb, were ligated by linker peptide (Gly4Ser)3 to form the single-chain Fv fragment (scFv). Then, the engineered antibody (LH1-3) was generated by fusing scFv with the entire IgG1 heavy constant regions. The 3-D structure of LH1-3 was modeled using computer-aided homology modeling method and the binding activity of LH1-3 was evaluated theoretically. Compared to the 3-D structure of the Fv fragment of the parent antibody, the conformation of the active pocket of LH1-3 was remained because of the rigid support of Cγ1.Further experimental results of flow cytometry showed that the engineered anti-CD20 antibody possessed specifically binding activity to CD20-expressing target cells. The anti-CD20 antibody fragments could also mediate complement-dependent cytotoxicity (CDC) of human B-lymphoid cell lines. Our study highlights some interests and advantages of a methodology based on the homology modeling and analysis of molecular structural properties.

  20. Induction of Apoptosis of Raji Cell by Chimeric Anti-CD20 Fab′ Fragment CTAM Based Dynamic Analysis of Large Astronautical Structure%嵌合抗CD20 Fab′诱导Raji细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    范冬梅; 赖增祖; 熊冬生; 许元富; 彭晖; 杨纯正

    2001-01-01

    为了研究嵌合抗CD20基因工程抗体Fab′的抗肿瘤活性及其抗肿瘤机制,利用3H掺入法测定嵌合抗CD20 Fab′对Raji细胞生长的影响,结果显示嵌合抗CD20 Fab′对Raji细胞的生长具有抑制作用,利用流式细胞仪测定嵌合抗CD20 Fab′诱导Raji细胞凋亡作用,结果显示嵌合抗CD20 Fab′可诱导Raji细胞凋亡作用.这些实验结果证明嵌合抗CD20 Fab′通过诱导Raji细胞凋亡的机制抑制Raji细胞生长.

  1. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

    Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

  2. Inhibition of Proliferation of Raji Cell by Chimeric Anti-CD20 Antibody Fab′ Fragment%嵌合抗CD20 Fab′对B淋巴瘤细胞Raji细胞生长的影响

    Institute of Scientific and Technical Information of China (English)

    范冬梅; 赖增祖; 熊冬生; 许元富; 彭晖; 杨纯正

    2001-01-01

    目的:研究嵌合抗CD20基因工程抗体Fab′的抗肿瘤活性.方法:利用MTT法以及3H掺入法测定嵌合抗CD20 Fab′对Raji细胞生长的影响.结果:MTT法测定结果显示嵌合抗CD20 Fab′对Raji细胞的生长具有抑制作用,抑制作用成剂量依赖性,其IC50为24μg/ml;嵌合抗CD20 Fab′对3H-TdR掺入Raji细胞无抑制作用,表明抗CD20 Fab′不影响Raji细胞DNA的合成;但嵌合抗CD20 Fab′抑制3H-UdR掺入Raji细胞,表明嵌合抗CD20 Fab′对Raji细胞RNA合成具有抑制作用,其抑制作用成剂量相关性.结论:嵌合抗CD20 Fab′抑制Raji细胞生长,嵌合抗CD20 Fab′具有较好的抗肿瘤活性.

  3. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity

    NARCIS (Netherlands)

    Moessner, Ekkehard; Bruenker, Peter; Moser, Samuel; Puentener, Ursula; Schmidt, Carla; Herter, Sylvia; Grau, Roger; Gerdes, Christian; Nopora, Adam; van Puijenbroek, Erwin; Ferrara, Claudia; Sondermann, Peter; Jaeger, Christiane; Strein, Pamela; Fertig, Georg; Friess, Thomas; Schuell, Christine; Bauer, Sabine; Dal Porto, Joseph; Del Nagro, Christopher; Dabbagh, Karim; Dyer, Martin J. S.; Poppema, Sibrand; Klein, Christian; Umana, Pablo

    2010-01-01

    CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall s

  4. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma

    OpenAIRE

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo; Klein, Christian

    2013-01-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of ob...

  5. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

    Science.gov (United States)

    Salles, Gilles; Morschhauser, Franck; Lamy, Thierry; Milpied, Noel; Thieblemont, Catherine; Tilly, Hervé; Bieska, Gabi; Asikanius, Elina; Carlile, David; Birkett, Joe; Pisa, Pavel; Cartron, Guillaume

    2012-05-31

    Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I Abs in vitro and in preclinical studies. In the present study, we evaluated the safety, efficacy, and pharmacokinetics of GA101 in a phase 1 study of 21 patients with heavily pretreated, relapsed, or refractory CD20(+) indolent NHL. Patients received GA101 in a dose-escalating fashion (3 per cohort, range 50/100-1200/2000 mg) for 8 × 21-day cycles. The majority of adverse events (AEs) were grades 1 and 2 (114 of 132 total AEs). Seven patients reported a total of 18 grade 3 or 4 AEs. Infusion-related reactions were the most common AE, with most occurring during the first infusion and resolving with appropriate management. Three patients experienced grade 3 or 4 drug-related infusion-related reactions. The best overall response was 43%, with 5 complete responses and 4 partial responses. Data from this study suggest that GA101 was well tolerated and demonstrated encouraging activity in patients with previously treated NHL up to doses of 2000 mg. This trial is registered at www.clinicaltrials.gov as NCT00517530.

  6. The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

    Science.gov (United States)

    Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

    2013-06-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

  7. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  8. In vitro characterization of {sup 177}Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Lohri, Andreas [Basel University Medical Clinic, Liestal (Switzerland); Moldenhauer, Gerhard [German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany)

    2009-09-15

    {sup 131}I- and {sup 90}Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either {sup 177}Lu or {sup 90}Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10{sup 5} times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m{sup 2} body surface {sup 177}Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of {sup 177}Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with {sup 177}Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. {sup 177}Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

  9. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  10. A Review of Obinutuzumab (GA101), a Novel Type II Anti-CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies.

    Science.gov (United States)

    Tobinai, Kensei; Klein, Christian; Oya, Naoko; Fingerle-Rowson, Günter

    2017-02-01

    Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies. Efficacy as monotherapy has been reported in patients with relapsed/refractory indolent and aggressive non-Hodgkin lymphoma (NHL) and in chronic lymphocytic leukemia (CLL) of B-cell origin. Improved outcomes have also been noted when obinutuzumab is added to chemotherapy in patients with B-cell NHL, and superiority over rituximab has been reported with combination therapy in patients with CLL. Ongoing research is focusing on developing options for chemotherapy-free treatment and on new combinations of obinutuzumab with novel targeted agents.

  11. Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

    Science.gov (United States)

    Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

    2016-01-20

    Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.

  12. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    Science.gov (United States)

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role

  13. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma.

    Science.gov (United States)

    Herting, Frank; Friess, Thomas; Bader, Sabine; Muth, Gunter; Hölzlwimmer, Gabriele; Rieder, Natascha; Umana, Pablo; Klein, Christian

    2014-09-01

    Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy.

  14. Quantitative Analysis of High Dose Radioimmunotherapy with I-131 Anti-CD20 Monoclonal Antibody (Rituximab) in Patients with Non-Hodgkin's Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyeong Min; Kang, Hye Jin; Choi, Tae Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Radioimmunotherapy (RIT) is therapeutic method for treatment of patient with incurable disease. I-131 is an radioisotope widely used for both diagnostic imaging and therapy, because of simultaneous emitting both gamma- and beta-ray. Recently, RIT using I-131 anti- CD20 rituximab has been introduced as one of the promising therapeutic model to treat patient with non- Hodgkin's Lymphoma (NHL). Although dosimetric approaches of low-dose I-131 rituximab imaging have been reported, there is no study of dosimetry with high dose imaging in patient with NHL yet. In this study, we evaluated strategy of high-dose RIT and investigated the kinetic behavior and absorbed dose to bone marrow and whole body in RIT study with high-dose strategy using I-131 rituximab for NHL.

  15. Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

    Science.gov (United States)

    Yang, Hsiang-Yu; Ke, Hung-Yen; Hong, Gou-Jieng; Tsai, Yi-Ting; Lin, Chih-Yuan; Li, Chung-Yi; Tsai, Chien-Sung

    2009-10-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

  16. In vitro characterization of a chimeric anti-CD20 antibody%抗CD20嵌和抗体的体外生物学活性研究

    Institute of Scientific and Technical Information of China (English)

    杨扬; 张大鹏; 郭怀祖; 吴兰; 聂丽; 钱卫珠; 李博华

    2010-01-01

    c8F6是我们实验室制备的一株抗CD20的鼠/人嵌合抗体.本研究对c8F6的体外生物学活性进行了测定并与临床上使用的CD20抗体Rituximab进行了比较.实验结果表明,c8F6具有与Rituximab相似的抗原结合活性,抗体依赖性细胞介导的细胞毒作用(ADCC),肿瘤细胞凋亡诱导活性及肿瘤细胞生长抑制作用.但c8F6的补体依赖性细胞毒作用(CDC)明显强于Rituximab,在10 μg/ml浓度时c8F6对Daudi细胞和Raji细胞的杀伤率分别为91%和86%,而Rituximab的杀伤率分别为65%(Daudi细胞)和32%(Raji细胞).研究结果提示,c8F6可能发展成为一个比Rituximab更为有效的用于治疗B细胞非霍奇金淋巴瘤的抗体制剂.

  17. Structure verification of a recombinant chimeric anti-CD20 IgG1 monoclonal antibody%重组嵌合抗CD20 IgG1型单克隆抗体的结构验证

    Institute of Scientific and Technical Information of China (English)

    陶磊; 饶春明; 高凯; 史新昌; 赵阳; 王军志

    2010-01-01

    本文选择一种重组嵌合抗CD20 IgG1型单抗.应用液质联用仪及N-末端测序仪对其进行结构验证.对该单抗进行还原、烷基化、酶解等处理后,对其氨基酸序列、二硫键配对方式、糖链类型及糖基化位点进行分析测定.结果显示,该单抗轻、重链氨基酸序列与理论一致.通过液质肽图的解析,对单抗10条二硫键的配对方式进行了验证;通过比较单抗重链切糖前、后的相对分子质量,预测单抗所含糖链类型为岩藻糖化的双触角复杂型N-糖,糖基化位点位于重链的Asn301上.本方法可为该类重组单抗制品的质量控制及其参考品的结构确证提供参考.

  18. Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Annicchiarico, B E; Siciliano, M; Avolio, A W; Agnes, S; Bombardieri, G

    2009-05-01

    Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

  19. The study of labeling with Iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma; Estudo de marcacao com Iodo-131 de anticorpo monoclonal anti-CD20 na terapia de linfoma nao-Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2006-07-01

    Lymphomas are malignancies of the lymphatic system, described by Thomas Hodgkin in 1932. Traditionally, lymphomas are classified in two basic groups: Hodgkin disease and non-Hodgkin lymphoma (NHL). Patients with NHL were earlier treated with radiotherapy alone or in combination with immunotherapy using monoclonal antibody anti-CD20 (ex., Rituximab-Mabthera, Roche). However, Radioimmunotherapy is a new modality of treatment for patients with NHL, in which cytotoxic radiation from therapeutic radioisotopes is delivered to tumors through monoclonal antibodies. This study focused on labeling conditions of monoclonal antibody anti-CD20 (Rituximab-Mabthera, Roche) with iodine-131, by direct radioiodination method using Chloramine-T as oxidizing agent. Labeling parameters investigated were: Radiochemical purity (RP), method of purification, incubation time, antibody mass, oxidative agent mass, stability in vitro, stability in vivo, immunoreactivity and biological distribution performed in normal Swiss mouse. Product of high radiochemical purity was obtained with no notable difference between the methods applied. No clear evidence of direct influence of incubation time on radiochemical purity of the labeled antibody was observed. Whereas, a clear evidence of direct influence of activity on radiochemical purity of the labeled antibody was observed when antibody mass was varied. After purification, the labeled product presented radiochemical purity of approximately 100 %. Product of superior radiochemical yield was observed when standard condition of labeling was used. The labeled product presented variation in radiochemical purity using five different stabilizer conditions. The condition in which gentisic acid was combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled with high therapeutic activity of iodine-131. The labeled product presented low immunoreactivity when compared to the literature. Biological distribution in

  20. 两种重组抗CD20人源化单克隆抗体定量分析方法的比较及其在药代动力学研究中的应用%Comparison of Two Quantitative Assays for Determination of Rh-anti-CD20 zumab and Their Application to Pharmacokinetic Study

    Institute of Scientific and Technical Information of China (English)

    邓承莲; 邹佳; 欧伦; 董立厚; 宋海峰

    2014-01-01

    An enzyme linked immunosorbent assay ( ELISA ) and a flow cytometry assay ( FCA ) based on Wil2-S cells were developed and systematically compared for quantification of recombinant anti-CD20 humanized monoclonal antibody ( rh-anti-CD20zumab) in biological matrix. The specificity, precision and accuracy of each method at correspondingly different linear range showed good results. For ELISA, the precisions of intra-day and inter-day were both <19 . 5%, the relative error was from-18 . 2% to 17 . 6%;For FCA, the precisions of intra-day and inter-day were both <19. 0%, the relative error was from -18. 9% to 18. 4%. The sensitivity of ELISA was significantly higher than that of FCA. The quantitative ranges of ELISA and FCA methods were 0. 04-5. 0 mg/L and 3. 1-200 mg/L, respectively. The concentrations in serum samples and pharmacokinetics analysis were determined by both of two methods after vein drip administration of rh-anti-CD20zumab in rhesus monkeys. Pharmacokinetics data showed that there was excellent consistency between results obtained by two methods at the given dose. We believe that the novel FCA with high speed and high sensitivity can be used to perform PK and PD study of cell surface antigen-targeted antibody derivatives.%采用酶联免疫吸附分析( ELISA)与基于Wil2-S细胞的流式细胞术( FCA)两种方法对生物基质中的重组抗CD20人源化单克隆抗体(rh-anti-CD20zumab)进行定量分析,并对两种方法进行系统比较。方法学验证结果表明,两种方法均具有良好的特异性、精密度和准确度,但定量范围存在明显差异。 ELISA法批内和批间精密度均小于19.5%,准确度为-18.2%~17.6%;FCA法批内和批间精密度均小于19.0%,准确度为-18.9%~18.4%。二者定量范围分别为0.04~5.0 mg/L和3.1~200 mg/L,ELISA法的灵敏度显著高于FCA法。利用两种方法测定猕猴静脉滴注 rh-anti-CD20zumab后的血药浓度-时间变化并进行药代动力学( PK)分析。结果表明,

  1. Circulating (CD3−CD19+CD20−IgD−CD27highCD38high) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy?

    Science.gov (United States)

    Beukinga, Ingrid; Willard-Gallo, Karen; Nortier, Joëlle; Pradier, Olivier

    2016-01-01

    Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3−CD19+CD20−IgD−CD27highCD38high), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3−CD19+CD20+IgD−CD27+CD38−) and naive (CD3−CD19+CD20+IgD+CD27−CD38low) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19+ B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19+ lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN. PMID:27493452

  2. Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

    Science.gov (United States)

    2016-06-13

    Adult Burkitt Lymphoma; Adult Diffuse Large B-Cell Lymphoma; CD20-Positive Neoplastic Cells Present; Indolent Adult Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

  3. Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

    Science.gov (United States)

    Bhati, Manjeet; Bandyopadhyay, Syamasis

    2016-08-01

    Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p treatment. The treatment was well tolerated by patients without any clinically relevant serious adverse events over 24 weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of csDMARD-failed patients with RA over a 6-month period.

  4. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William;

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  5. Establishment of a novel model suitable to evaluate the antitumor activity of anti-CD20 antibodies%一种适用于评价CD20抗体体内外抗肿瘤效应模型的建立

    Institute of Scientific and Technical Information of China (English)

    刘广洛; 钱卫珠; 李博华; 杨扬; 许静; 王皓

    2010-01-01

    研究通过基因转染的方法建立了稳定表达不同水平人CD20分子的小鼠骨髓瘤细胞克隆:CD20高表达(NS1CD20H)、中表达(NS1-CD20M)和低表达(NS1-CD20L)的NS-1细胞株.利用建立的CD20分子高、中、低表达的NS-1细胞系,我们初步研究了CD20分子表达水平与CD20抗体杀伤活性的关系.实验结果表明,随着CD20分子表达水平的提高,CD20抗体(Rituximab和2F2)的CDC和ADCC作用均相应增强.2F2抗体具有与Rituximab相似的ADCC作用.对于CD20高表达细胞,2F2抗体显示出和Rituximab相似的CDC活性.但对于CD20低表达的NS-1细胞,2F2的CDC活性远强于Rituximab.体内实验结果表明对于荷有NS1-CD20L的小鼠,Rituximab不能显示出抗肿瘤活性,而2F2则具有显著的抗肿瘤作用.由于这两个抗体有相似的ADCC活性,实验结果提示CDC可能是CD20抗体的重要作用机制之一.我们建立的不同程度表达CD20的NS-1细胞克隆可以成为一种新型的CD20抗体活性评价模型,并有助于进一步阐明CD20抗体的作用机制.

  6. Targeting CD20 in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Nahas MR

    2015-03-01

    Full Text Available Myrna R Nahas, Jon E ArnasonBeth Israel Deaconess Medical Center, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL, the most common leukemia in adults, is standardly managed with chemotherapy in combination with the anti-CD20 antibody rituximab. In this review, we discuss the history, use, and evolution of rituximab in the treatment of CLL and explore the next generation CD20 antibodies ofatumumab and obinutuzumab with a focus on recent clinical trials. Increased understanding of the importance of B cell receptor (BCR signaling in CLL has resulted in the development of several drugs with significant clinical activity that are ideally suited for combination with CD20 therapy as is being currently explored. Moving forward, these developments have the potential to result in treatment regimens that do not include traditional chemotherapeutic agents, which is of particular importance in CLL given the late onset of diagnosis and potential frailty of the patients.Keywords: CLL, monoclonal antibody, rituximab, ofatumumab, obinutuzumab

  7. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  8. CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究%Clinical study of autologous peripheral blood stem cell transplantation combined with anti-CD20 monoclonal antibody in non-Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    蔡宇; 王椿; 姜杰玲; 杨隽; 颜式可; 万理萍

    2010-01-01

    目的 探讨抗CD20单克隆抗体(利妥昔单抗,商品名:美罗华)联合自体外周血干细胞移植(APBSCT)治疗B细胞非霍奇金淋巴瘤(NHL)的疗效.方法 21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解(CR),难治性病例为16例,包括11例部分缓解(PR)和5例疾病进展(PD).在自体造血干细胞动员的第1、8天及预处理的-1、+7天每天应用利妥昔单抗375 mg/m2.结果 移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存.21例患者中位随访24(1~68)个月,复发、死亡4例(19%),其余17例均无病生存,2年无病生存(EFS)和总生存(OS)率均为81.0%.未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响.结论 APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS.利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建.%Objective To evaluate the efficacy of anti-CD20 monoclonal antibody (Rituximab) combined with autologous hematopoietic stem cell transplant (ASCT) in treatment of the patients with B cell non-Hodgkin lymphoma (NHL). Methods Twenty-one patients with B-cell NHL(CD20 positive) received ASCT with Rituximab at the dose of 385 mg·m-2·d-1 on day 1 and day 8 of mobilization,and day -1 and day +7 of conditioning regimen. Among the 21 patients receiving chemotherapy before the transplant, five cases achieved complete response (CR), eleven cases achieved partial remission (PR), and 5 cases had the progression of disease (PD) after many cycles of chemotherapy. Results The median follow-up was 24 months (1-68 months) in the present study. No relapse occurred among the 5 patients in CR before the

  9. Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.

    Science.gov (United States)

    Sharman, Jeff P; Farber, Charles M; Mahadevan, Daruka; Schreeder, Marshall T; Brooks, Heather D; Kolibaba, Kathryn S; Fanning, Suzanne; Klein, Leonard; Greenwald, Daniel R; Sportelli, Peter; Miskin, Hari P; Weiss, Michael S; Burke, John M

    2017-02-01

    Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

  10. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in {sup 131}I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Boucek, Jan A. [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); Turner, J. Harvey [Fremantle Hospital, Department of Nuclear Medicine, Fremantle (Australia); University of Western Australia, School of Medicine and Pharmacology (Australia)

    2005-04-01

    Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of {sup 131}I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT. (orig.)

  11. Non-clinical study and evaluation thinking of biosimilar products in China: reviewing the case of anti-CD20 monoclonal antibody%从抗CD20单抗探讨我国生物类似药非临床研究与评价的思路

    Institute of Scientific and Technical Information of China (English)

    余珊珊; 胡晓敏; 王海学; 王庆利; 于冰

    2015-01-01

    CFDA发布《生物类似药研发与评价技术指导原则(试行)》,明确了生物类似药非临床研究和评价中的基本原则.国内外研发生物类似药成为热点,本文结合国内外相关指导原则的要求和国内抗CD20单抗品种的审评,讨论我国生物类似药非临床研究评价的思路.

  12. Detecting CD20-Rituximab specific interactions on lymphoma cells using atomic force microscopy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Elucidating the underlying mechanisms of cell physiology is currently an important research topic in life sciences. Atomic force microscopy methods can be used to investigate these molecular mechanisms. In this study, single-molecule force spectroscopy was used to explore the specific recognition between the CD20 antigen and anti-CD20 antibody Rituximab on B lymphoma cells under near-physiological conditions. The CD20-Rituximab specific binding force was measured through tip functionalization. Distribution of CD20 on the B lymphoma cells was visualized three-dimensionally. In addition, the relationship between the intramolecular force and the molecular extension of the CD20-Rituximab complex was analyzed under an external force. These results facilitate further investigation of the mechanism of Rituximab’s anti-cancer effect.

  13. CD20 monoclonal antibody targeted nanoscale drug delivery system for doxorubicin chemotherapy: an in vitro study of cell lysis of CD20-positive Raji cells.

    Science.gov (United States)

    Jiang, Shuang; Wang, Xiaobo; Zhang, Zhiran; Sun, Lan; Pu, Yunzhu; Yao, Hongjuan; Li, Jingcao; Liu, Yan; Zhang, Yingge; Zhang, Weijing

    A monoclonal antibody targeted nanoscale drug delivery system (NDDS) for chemotherapy was evaluated in CD20-positive Raji cells in vitro. Nanoparticles were formed by the assembly of an amphiphilic polymer consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypolyethyleneglycol-2000 (DSPE-PEG2000). Active carbon nanoparticles (ACNP) were conjugated to the chemotherapeutic agent, doxorubicin (DOX), and the nanoliposome carrier, DSPE-PEG2000 and DSPE-PEG2000-NH2 conjugated to the human anti-CD20 monoclonal antibody that targets B-lymphocytes. This monoclonal antibody targeted nanoparticle delivery system for chemotherapy formed the active NDDS complex, ACNP-DOX-DSPE-PEG2000-anti-CD20. This active NDDS was spherical in morphology and had good dispersion in the culture medium. When compared with the effects on CD20-negative YTS cells derived from natural killer/T-cell lymphoma, the active NDDS, ACNP-DOX-DSPE-PEG2000-anti-CD20, demonstrated DOX delivery to CD20-positive Raji cells derived from Burkitt's lymphoma (B cell lymphoma), resulting in increased cell killing in vitro. The intracellular targeting efficiency of the ACNP-DOX-DSPE-PEG2000-anti-CD20 complex was assessed by confocal laser microscopy and flow cytometry. The findings of this in vitro study have shown that the DSPE-PEG2000 polymeric liposome is an effective nanocarrier of both a monoclonal antibody and a chemotherapy agent and can be used to target chemotherapy to specific cells, in this case to CD20-positive B-cells. Future developments in this form of targeted therapy will depend on the development of monoclonal antibodies that are specific for malignant cells, including antibodies that can distinguish between lymphoma cells and normal lymphocyte subsets.

  14. Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

    Science.gov (United States)

    Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

    2017-03-01

    The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

  15. Phosphine-boranes as bidentate ligands: formation of [8,8-eta(2)-(eta(2)-(BH(3)).dppm)-nido-8,7-RhSB(9)H(10)] and [9,9-eta(2)-(eta(2)-(BH(3)).dppm)-nido-9,7,8-RhC(2)B(8)H(11)] from [8,8-(eta(2)-dppm)-8-(eta(1)-dppm)-nido-8,7-RhSB(9)H(10)] and [9,9-(eta(2)-dppm)-9-(eta(1)-dppm)-nido-9,7,8-RhC(2)B(8)H(11)], respectively.

    Science.gov (United States)

    Volkov, Oleg; Macías, Ramón; Rath, Nigam P; Barton, Lawrence

    2002-11-04

    The two clusters [8,8-(eta(2)-dppm)-8-(eta(1)-dppm)-nido-8,7-RhSB(9)H(10)] (1) and [9,9-(eta(2)-dppm)-9-(eta(1)-dppm)-nido-9,7,8-RhC(2)B(8)H(11)] (2) (dppm = PPh(2)CH(2)PPh(2)), both of which contain pendant PPh(2) groups, react with BH(3).thf to afford the species [8,8-eta(2)-(eta(2)-(BH(3)).dppm)-nido-8,7-RhSB(9)H(10)] (3) and [9,9-eta(2)-(eta(2)-(BH(3)).dppm))-nido-9,7,8-RhC(2)B(8)H(11)] (4), respectively. These two species are very similar in that they both contain the bidentate ligand [(BH(3)).dppm], which coordinates to the Rh center via a PPh(2) group and also via a eta(2)-BH(3) group. Thus, the B atom in the BH(3) group is four-coordinate, bonded to Rh by two bridging hydrogen atoms, to a terminal H atom, and to a PPh(2) group. At room temperature, the BH(3) group is fluxional; the two bridging H atoms and the terminal H atom are equivalent on the NMR time scale. The motion is arrested at low temperature with DeltaG++ = ca. 37 and 42 kJ mol(-1), respectively, for 3 and 4. Both species are characterized completely by NMR and mass spectral measurements as well as by elemental analysis and single-crystal structure determinations.

  16. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis.

    Science.gov (United States)

    Pavlasova, Gabriela; Borsky, Marek; Seda, Vaclav; Cerna, Katerina; Osickova, Jitka; Doubek, Michael; Mayer, Jiri; Calogero, Raffaele; Trbusek, Martin; Pospisilova, Sarka; Davids, Matthew S; Kipps, Thomas J; Brown, Jennifer R; Mraz, Marek

    2016-09-22

    Agents targeting B-cell receptor (BCR) signaling-associated kinases such as Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase can induce mobilization of neoplastic B cells from the lymphoid tissues into the blood, which makes them potentially ideal to combine with anti-CD20 monoclonal antibodies (such as rituximab, obinutuzumab, or ofatumumab) for treatment of B-cell lymphomas and chronic lymphocytic leukemia (CLL). Here we show that interactions between leukemia cells and stromal cells (HS-5) upregulate CD20 on CLL cells and that administering ibrutinib downmodulates CD20 (MS4A1) expression in vivo. We observed that CLL cells that have recently exited the lymph node microenvironment and moved into the peripheral blood (CXCR4(dim)CD5(bright) subpopulation) have higher cell surface levels of CD20 than the cells circulating in the bloodstream for a longer time (CXCR4(bright)CD5(dim) cells). We found that CD20 is directly upregulated by CXCR4 ligand stromal cell-derived factor 1 (SDF-1α, CXCL12) produced by stromal cells, and BTK-inhibitor ibrutinib and CXCR4-inhibitor plerixafor block SDF-1α-mediated CD20 upregulation. Ibrutinib also downmodulated Mcl1 levels in CLL cells in vivo and in coculture with stromal cells. Overall, our study provides a first detailed mechanistic explanation of CD20 expression regulation in the context of chemokine signaling and microenvironmental interactions, which may have important implications for microenvironment-targeting therapies.

  17. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20.

    Science.gov (United States)

    Teeling, Jessica L; Mackus, Wendy J M; Wiegman, Luus J J M; van den Brakel, Jeroen H N; Beers, Stephen A; French, Ruth R; van Meerten, Tom; Ebeling, Saskia; Vink, Tom; Slootstra, Jerry W; Parren, Paul W H I; Glennie, Martin J; van de Winkel, Jan G J

    2006-07-01

    We have previously defined a panel of fully human CD20 mAb. Most of these were unexpectedly efficient in their ability to recruit C1q to the surface of CD20-positive cells and mediate tumor lysis via activation of the classical pathway of complement. This complement-dependent cytotoxicity (CDC) potency appeared to relate to the unusually slow off-rate of these human Abs. However, we now present epitope-mapping data, which indicates that all human mAb bind a novel region of CD20 that may influence CDC potency. Epitope mapping, using both mutagenesis studies and overlapping 15-mer peptides of the extracellular loops of CD20, defined the amino acids required for binding by an extensive panel of mouse and human mAb. Binding by rituximab and mouse CD20 mAb, had an absolute requirement for alanine and proline at positions 170 and 172, respectively, within the large extracellular loop of CD20. Surprisingly, however, all of the human CD20 mAb recognize a completely novel epitope located N-terminally of this motif, also including the small extracellular loop of CD20. Thus, although off-rate may influence biological activity of mAb, another critical factor for determining CDC potency by CD20 mAb appears to be the region of the target molecule they recognize. We conclude that recognition of the novel epitope cooperates with slow off-rate in determining the activity of CD20 Ab in activation of complement and induction of tumor cell lysis.

  18. Functional Recombinant Extra Membrane Loop of Human CD20, an Alternative of the Full Length CD20 Antigen

    OpenAIRE

    Anbouhi, Mahdi Habibi; Baraz, Aida Feiz; Bouzari, Saeid; Abolhassani,Mohsen; Khanahmad, Hossein; Golkar, Majid; Aghasadeghi, Mohammad Reza; Behdani, Mahdi; Najafabadi, Ali Jahanian; Shokrgozar, Mohammad Ali

    2012-01-01

    Background: Targeting of CD20 antigen with monoclonal antibodies has become the mainstay in the treatment of non-Hodgkin's lymphomas and immunotherapeutic depletion of malignant B cells. Accessibility of antigen is one of the crucial factors in development of monoclonal antibodies against this antigen. One major problem in expression of full length CD20 is aggregation and misfolding. Therefore, production of an alternative polypeptide is easer and favorable comparing to that of a full length ...

  19. New heavy-fermion antiferromagnet UPd2Cd20

    Science.gov (United States)

    Hirose, Yusuke; Doto, Hiroshi; Honda, Fuminori; Li, Dexin; Aoki, Dai; Haga, Yoshinori; Settai, Rikio

    2016-10-01

    We succeeded in growing a new high quality single crystal of a ternary uranium compound UPd2Cd20. From the electrical resistivity, magnetization, magnetic susceptibility, and specific heat experiments, UPd2Cd20 is found to be an antiferromagnetic heavy-fermion compound with the Néel temperature {{T}\\text{N}}   =  5 K and exhibits the large electronic specific heat coefficient γ exceeding 500 mJ (K2· mol)-1. This compound is the first one that exhibits the magnetic ordering with the magnetic moments of the U atom in a series of UT2X20 (T: transition metal, X  =  Al, Zn, Cd). UPd2Cd20 shows typical characteristic features in heavy-fermion systems such as a broad maximum in the magnetic susceptibility at {{T}{{χ\\text{max}}}} and a large coefficient A of T 2 term in the resistivity.

  20. CD20(+) B Cell Depletion Alters T Cell Homing

    NARCIS (Netherlands)

    Kap, Yolanda S.; van Driel, Nikki; Laman, Jon D.; Tak, Paul P.; 't Hart, Bert A.

    2014-01-01

    Depleting mAbs against the pan B cell marker CD20 are remarkably effective in the treatment of autoimmune-mediated inflammatory disorders, but the underlying mechanisms are poorly defined. The primary objective of this study was to find a mechanistic explanation for the remarkable clinical effect of

  1. The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine.

    Directory of Open Access Journals (Sweden)

    Saurabh Jain

    Full Text Available Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2 that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7 isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a

  2. The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine.

    Science.gov (United States)

    Jain, Saurabh; Aresu, Luca; Comazzi, Stefano; Shi, Jianguo; Worrall, Erin; Clayton, John; Humphries, William; Hemmington, Sandra; Davis, Paul; Murray, Euan; Limeneh, Asmare A; Ball, Kathryn; Ruckova, Eva; Muller, Petr; Vojtesek, Borek; Fahraeus, Robin; Argyle, David; Hupp, Ted R

    2016-01-01

    Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2) that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv) into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7) isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a recombinant anti-CD20

  3. Reactive oxygen species induced by therapeutic CD20 antibodies inhibit natural killer cell-mediated antibody-dependent cellular cytotoxicity against primary CLL cells

    Science.gov (United States)

    Werlenius, Olle; Aurelius, Johan; Hallner, Alexander; Akhiani, Ali A.; Simpanen, Maria; Martner, Anna; Andersson, Per-Ola; Hellstrand, Kristoffer; Thorén, Fredrik B.

    2016-01-01

    The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL. PMID:27097113

  4. Construction and characterization of monoclonal antibodies against the extracellular domain of B-lymphocyte antigen CD20 using DNA immunization method.

    Science.gov (United States)

    Khademi, Fatemeh; Mostafaie, Ali; Parvaneh, Shahram; Gholami Rad, Farah; Mohammadi, Pantea; Bahrami, Gholamreza

    2017-02-01

    To date, several new anti-CD20 monoclonal antibodies (mAbs) have been developed for potential efficacies compared with familiar mAb rituximab. Despite the recent advances in development of anti-CD20 mAbs for the treatment of B cell malignancies, the efforts should be continued to develop novel antibodies with improved properties. However, the development of mAbs against CD20 as a multi-transmembrane protein is challenging due to the difficulty of providing a lipid environment that can maintain native epitopes. To overcome this limitation, we describe a simple and efficient DNA immunization strategy for the construction of a novel anti-CD20 mAb with improved anti-tumour properties. Using a DNA immunization strategy that includes intradermal (i.d.) immunization with naked plasmid DNA encoding the CD20 gene, we generated the hybridoma cell line D4, which secretes functional mAbs against an extracellular epitope of CD20. Immunocytochemistry analysis and a cell-based enzyme-linked immunosorbent assay using a Burkitt's lymphoma cell line showed that D4 mAbs are capable of binding to native extracellular epitopes of CD20. Moreover, the binding specificity of D4 mAbs was determined by western blot analysis. Cell proliferation was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by the annexin V/propidium iodide staining and dye exclusion assay. The results showed that D4 anti-CD20 mAbs produced by DNA immunization exhibit potent growth inhibitory activity and have superior direct B-cell cytotoxicity compared to rituximab. We propose that antibody-induced apoptosis is one of the mechanisms of cell growth inhibition. Taken together, the data reported here open the path to DNA-based immunization for generating pharmacologically active monoclonal antibodies against CD20. In addition, the data support future in vivo animal testing and subsequent procedures to produce a potential therapeutic mAb.

  5. Screen of CD20 mimotope using monoclonal antibody Rituximab%CD20抗原模拟表位的筛选

    Institute of Scientific and Technical Information of China (English)

    吴守振; 张阔; 李萌; 贺丽清; 秦鑫; 张英起

    2009-01-01

    目的:筛选CD20分子的模拟表位肽,构建针对CD20分子的治疗性疫苗,以期为淋巴瘤以及其它B细胞相关性疾病的治疗提供新的方向.方法:利用噬菌体随机呈现肽库筛选技术,以人淋巴细胞分化抗原CD20 mAb Rituximab为靶点,筛选CD20分子的模拟表位肽.通过ELISA方法检测筛选出的阳性噬菌体与Rituximab的特异性结合,并以竞争性结合实验检测筛选出的阳性噬菌体与Raji细胞表面的CD20分子竞争结合Rituximab的能力.最后以Sanger双脱氧链终止法测定DNA序列,推断其氨基酸序列.结果:成功筛选出针对CD20 mAb Rituximab的阳性噬菌体,获得了CD20分子的模拟表位肽QDKLTQWPKWLE.获得的阳性噬菌体能够与Rituximab特异性结合,并且表达该表位的噬菌体可以竞争性抑制Rituximab与天然CD20分子的结合.结论:CD20分子的抗原表位肽QDKLTQWPKWLE能够与mAb Rituximab特异性结合,与天然CD20分子竞争性结合mAb Rituximab,并具有潜在的应用价值.

  6. Activatory and inhibitory Fcγ receptors augment rituximab-mediated internalization of CD20 independent of signaling via the cytoplasmic domain.

    Science.gov (United States)

    Vaughan, Andrew T; Chan, Claude H T; Klein, Christian; Glennie, Martin J; Beers, Stephen A; Cragg, Mark S

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes.

  7. CD20 therapies in multiple sclerosis and experimental autoimmune encephalomyelitis - Targeting T or B cells?

    Science.gov (United States)

    Agahozo, Marie Colombe; Peferoen, Laura; Baker, David; Amor, Sandra

    2016-09-01

    MS is widely considered to be a T cell-mediated disease although T cell immunotherapy has consistently failed, demonstrating distinct differences with experimental autoimmune encephalomyelitis (EAE), an animal model of MS in which T cell therapies are effective. Accumulating evidence has highlighted that B cells also play key role in MS pathogenesis. The high frequency of oligoclonal antibodies in the CSF, the localization of immunoglobulin in brain lesions and pathogenicity of antibodies originally pointed to the pathogenic role of B cells as autoantibody producing plasma cells. However, emerging evidence reveal that B cells also act as antigen presenting cells, T cell activators and cytokine producers suggesting that the strong efficacy of anti-CD20 antibody therapy observed in people with MS may reduce disease progression by several different mechanisms. Here we review the evidence and mechanisms by which B cells contribute to disease in MS compared to findings in the EAE model.

  8. Human umbilical cord-drived mesenchymal stem cells as vehicles of CD20 specific-TRAIL fusion protein against non-Hodgkin’ s lymphoma%脐带间充质干细胞运载scFvCD20:sTRAIL融合蛋白对B-淋巴瘤细胞的生长抑制作用

    Institute of Scientific and Technical Information of China (English)

    范冬梅; 张晓龙; 张晴; 卢杨; 杨圆圆; 袁向飞; 张砚君; 熊冬生

    2016-01-01

    migrated to tumor site, secreted a novel fusion protein scFvCD20:sTRAIL,and thus locally concentrated scFvCD20:sTRAIL extended antigen-restricted anti-tumor activity. The engineered HUMSCs secreting scFvCD20:sTRAIL showed potent effect on inhibiting tumor growth in BJAB lymphoma malignancy,which may play an essential role in the clinical research .%目的::探讨脐带间充质干细胞运载scFvCD20:sTRAIL融合蛋白的新型双重靶向系统对CD20+ BJAB细胞的生长抑制作用。方法:采用传统分子生物学技术构建 pLenR. scFvCD20:sTRAIL、pLenR. ISZ-sTRAIL、pLenR. scFvCD20及pLenR. copGFP四种慢病毒表达载体,利用四质粒慢病毒包装系统于293T细胞中包装慢病毒颗粒,并感染人脐带组织来源的MSCs( HUMSCs),使其稳定表达融合蛋白。于体外采用CCK8细胞增殖抑制实验检测scFvCD20:sTRAIL融合蛋白对CD20阳性BJAB细胞和Raji细胞、CD20阴性Jurkat细胞以及正常人外周血单个核细胞( PBMCs)的生长抑制作用。建立NOD/SCID鼠BJAB细胞皮下移植瘤模型,将MSC. scFvCD20:sTRAIL经尾静脉注射入小鼠体内,每3 d测量瘤体积,根据肿瘤体积计算抑瘤率。结果:成功构建了慢病毒表达载体pLenR. scFvCD20:sTRAIL、 pLenR. ISZ-sTRAIL、pLenR. scFvCD20及pLenR. copGFP,且经慢病毒感染可在HUMSCs中稳定表达。体外实验显示,scFvCD20:sTRAIL融合蛋白可不同程度地提高对CD20阳性BJAB和Raji细胞的生长抑制作用,而对CD20阴性Jurkat细胞的生长抑制作用降低;而且不影响PBMCs的生长。体内实验表明, MSC. scFvCD20:sTRAIL可显著抑制BJAB淋巴瘤的生长,初始治疗后第24天,抑瘤率达65.2%,与MSC. ISZ:sTRAIL治疗组比较(抑瘤率为52.7%),具统计学差异(P<0.05)。结论:建立了HUMSCs运载scFvCD20:sTRAIL融合蛋白的双重靶向治疗系统,HUMSCs可向BJAB淋巴瘤部位归巢并表达分泌scFvCD20:sTRAIL融合蛋白,后者在局部经scFvCD20的二次导向发挥CD20特异

  9. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab.

    Science.gov (United States)

    Golay, Josée; Da Roit, Fabio; Bologna, Luca; Ferrara, Claudia; Leusen, Jeanette H; Rambaldi, Alessandro; Klein, Christian; Introna, Martino

    2013-11-14

    Obinutuzumab (GA101) is a glycoengineered type 2 CD20 antibody with enhanced CD16A-binding and natural killer-mediated cytotoxicity. CD16B is highly homologous to CD16A and a major FcγR on human polymorphonuclear neutrophils (PMNs). We show here that glycoengineered obinutuzumab or rituximab bound CD16B with approximately sevenfold higher affinity, compared with nonglycoengineered wild-type parental antibodies. Furthermore, glycoengineered obinutuzumab activated PMNs, either purified or in chronic lymphoblastic leukemia whole blood, more efficiently than wild-type rituximab. Activation resulted in a 50% increase in CD11b expression and 70% down-modulation of CD62L on neutrophils and in release of tumor necrosis factor alpha, IL-6, and IL-8. Activation was not accompanied by generation of reactive oxygen species or antibody-dependent cellular cytotoxicity activity, but led to up to 47% phagocytosis of glycoengineered anti-CD20 opsonized chronic lymphoblastic leukemia targets by purified PMNs. Significant phagocytosis was observed in whole blood, but only in the presence of glycoengineered antibodies, and was followed by up to 50% PMN death. Finally we show, using anti-CD16B and anti-CD32A Fab and F(ab')2 fragments, that both of these receptors are involved in PMN activation, phagocytosis, and cell death induced by glycoengineered antibodies. We conclude that phagocytosis by PMNs is an additional mechanism of action of obinutuzumab mediated through its higher binding affinity for CD16B.

  10. The predictive significance of CD20 expression in B-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Horvat Mateja

    2011-04-01

    Full Text Available Abstract Background In our recent study, we determined the cut-off value of CD20 expression at the level of 25 000 molecules of equivalent soluble fluorochrome (MESF to be the predictor of response to rituximab containing treatment in patients with B-cell lymphomas. In 17.5% of patients, who had the level of CD20 expression below the cut-off value, the response to rituximab containing treatment was significantly worse than in the rest of the patients with the level of CD20 expression above the cut-off value. The proportion of patients with low CD20 expression who might not benefit from rituximab containing treatment was not necessarily representative. Therefore the aim of this study was to quantify the CD20 expression in a larger series of patients with B-cell lymphomas which might allow us to determine more reliably the proportion of patients with the CD20 expression below the cut-off. Methods Cytological samples of 64 diffuse large B-cell lymphomas (DLBCL, 56 follicular lymphomas (FL, 31 chronic lymphocytic leukemias (CLL, 34 mantle cell lymphomas (MCL, 18 marginal zone lymphomas (MZL and 15 B-cell lymphomas unclassified were analyzed for CD20 expression by quantitative four-color flow cytometric measurements using FACSCalibur flow cytometer (BD Biosciences. Results The range of CD20 expression in different B-cell lymphomas was very broad, varying from 2 737 to 115 623 MESF in CLL and 3 549 to 679 577 MESF in DLBCL. However, when we compared the CD20 expression in the groups of patients with DLBCL, FL, MCL, MZL, CLL and B-cell lymphomas unclassified, it was found to be significantly lower (p = 0.002 only in CLL but did not significantly differ in other lymphoma types (p = NS. Fifty-three out of 218 (24.3% patients with B-cell lymphomas had the CD20 expression below the cut-off value. Conclusions The CD20 expression in CLL is significantly lower than in most histological types of mature B-cell lymphomas in which it appears to be comparable

  11. Two courses of rituximab (anti-CD20 monoclonal antibody) for recalcitrant pemphigus vulgaris

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disease involving the skin and mucous membranes. The response to therapy varies greatly amongst patients and treatment may be challenging. Rituximab is a chimeric monoclonal antibody that selectively targets cell surface antigen...

  12. The anti-CD20 antibody rituximab reduces the Th17 cell response

    NARCIS (Netherlands)

    Veerdonk, F.L. van de; Lauwerys, B.; Marijnissen, R.J.; Timmermans, K.; Padova, F.E. Di; Koenders, M.M.J.F.; Gutierrez-Roelens, I.; Durez, P.; Netea, M.G.; Meer, J.W. van der; Berg, W.B. van den; Joosten, L.A.B.

    2011-01-01

    OBJECTIVE: Rituximab has been shown to be successful in the treatment of rheumatoid arthritis (RA), and this unexpected finding indicates that B cells have an important role in this disease. The present study was undertaken to investigate the mechanism of action of rituximab in RA. METHODS: Twelve p

  13. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

    DEFF Research Database (Denmark)

    Braendstrup, Peter; Bjerrum, Ole W; Nielsen, Ove J;

    2005-01-01

    with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50-100 mg of Pred given as premedication together with an antihistamine just before infusion...

  14. Preparation, quality control and biodistribution studies of [{sup 67}Ga]-DOTA-anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Jalilian, A.R.; Khorrami, A. [Nuclear Science and Technology Research Inst., Karaj (IR). Nuclear Medicine Research Group, Agriculture, Medicine and Industrial Research School (AMIRS); Mirsadeghi, L.; Haji-Hosseini, R. [Payam-e-Noor Univ., Tehran (Iran). Biochemistry Dept.

    2008-07-01

    Rituximab was successively labeled with [{sup 67}Ga]-gallium chloride. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH{sub 2}Cl{sub 2}. DOTA-Rituximab was obtained by the addition of 1 mL of a Rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH=7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 C in 3 h. Radio-thin layer chromatography showed an overall radiochemical purity of 90%-95% at optimized conditions (specific activity = 30 GBq/mg, labeling efficacy; 82%). The final isotonic {sup 67}Ga-DOTA-rituximab complex was checked by gel electrophoresis for radiolysis. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 {mu}m filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h. (orig.)

  15. Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab).

    Science.gov (United States)

    Pinto, Luis Fernando; Candia, Liliana; Garcia, Patricia; Marín, Juan Ignacio; Pachón, Ines; Espinoza, Luis R; Marquez, Javier

    2009-01-01

    We report a 19-year-old female with systemic lupus erythematosus and lupus nephritis who developed pulmonary hemorrhage (PH) refractory to conventional immunosuppressive treatment. She was initially treated with intravenous methylprednisolone and cyclophosphamide pulses. She required mechanical ventilation due to a lack of responsiveness and her disease was considered refractory to conventional treatment. Rituximab was administered and this was followed by clinical improvement in both PH and nephritis. Rituximab may be a useful therapeutic option for the treatment of refractory PH.

  16. CD19(+) CD20(-) CD27(hi) IL-s10-producing B cells are overrepresented in R-CHOP-treated DLBCL patients in complete remission.

    Science.gov (United States)

    Qiu, Huiying; Li, Junguo; Feng, Zhenjun; Yuan, Joanna; Lu, Jie; Hu, Xiaoxia; Gao, Lei; Lv, Shuqing; Yang, Jianmin; Chen, Lei

    2016-09-01

    Treatment of diffuse large B cell lymphoma (DLBCL) with rituximab, an anti-CD20 monoclonal antibody, has resulted in significantly improved patient responses with longer event-free intervals and higher overall survival rates. However, since rituximab depletes all CD20-expressing cells, including noncancerous B cells, the effects of rituximab on the normal immunity of DLBCL patients under remission need to be examined. Here, we observed that DLBCL patients under remission contained significantly lower frequencies of total B cells, with a significantly overrepresented interleukin (IL)-10-producing B cell (B10) population in the peripheral blood. Further examination confirmed that a large fraction of B10 cells was CD20(-) CD27(hi) plasmablasts, possibly explaining the persistence of B10 cells after R-CHOP treatment. We also observed that the percentage of B10 cells in DLBCL patients in remission gradually reduced during the first year of achieving complete remission, primarily due to the replenishment of non-B10 B cells. Despite this, the percentage of B10 cells in DLBCL patients after 1 year of achieving complete remission was still higher than that in controls. CD4(+) and CD8(+) T cells cocultured with B10-enriched B cells secreted significantly lower levels of proinflammatory cytokines IFN-g and TNF-a, compared to those incubated with B10-depleted B cells. Together, our data observed a long-lasting overrepresentation of B10 cells in DLBCL patients under remission. Whether this change could impact on the overall anti-tumor immunity during remission requires further studies.

  17. Estudo dos linfócitos CD20, CD8 e CD4 nas hiperplasias inflamatórias e sua relação com a infecção por candida sp

    OpenAIRE

    Cristiano Macabú Badauy

    2003-01-01

    O objetivo do presente estudo é mapear e quantificar as populações de células CD 20, CD 8 e CD 4+ em Hiperplasias inflamatórias (HI) e estabelecer relação com a infecção por Candida sp. Foram utilizados 41 casos de HI do Laboratório de Patologia Bucal da UFRGS. Novos cortes de todos os casos foram submetidos à técnica de coloração do PAS, criando – se 2 grupos: com e sem infecção por Candida sp. Seguiu – se a marcação imunohistoquímica com os anticorpos monoclonais anti CD 20, anti CD 8 e ant...

  18. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies

    NARCIS (Netherlands)

    Niederfellner, G.; Lammens, A.; Mundigl, O.; Georges, G.J.; Schaefer, W.; Schwaiger, M.; Franke, A.; Wiechmann, K.; Jenewein, S.; Slootstra, J.W.; Timmerman, P.; Brännström, A.; Lindstrom, F.; Mössner, E.; Umana, P.; Hopfner, K.P.; Klein, C.

    2011-01-01

    CD20 is a cell-surface marker of normal and malignant B cells. Rituximab, a monoclonal antibody targeting CD20, has improved the treatment of malignant lymphomas. Therapeutic CD20 antibodies are classified as either type I or II based on different mechanisms of killing malignant B cells. To reveal t

  19. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies.

    Science.gov (United States)

    Sehn, Laurie H; Assouline, Sarit E; Stewart, Douglas A; Mangel, Joy; Gascoyne, Randy D; Fine, Gregg; Frances-Lasserre, Susan; Carlile, David J; Crump, Michael

    2012-05-31

    This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance. Cohorts of 3 to 6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months, for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least 1 rituximab-containing regimen. No dose-limiting or unexpected AEs were observed. Infusion-related reactions were most common (all grades, 73%; grade 3/4, 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%), and nausea (18%). At end of induction, 5 (23%) patients achieved partial responses and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 partial responses/1 complete response). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation. This study was registered at www.clinicaltrials.gov (identifier NCT00576758).

  20. Acellbia® and Mabtera® are recognize CD20-positive cells with equal efficiency

    Directory of Open Access Journals (Sweden)

    V. A. Misyurin

    2015-01-01

    Full Text Available In present study were compared characteristics of rituximab produced by Hoffmann–La Roche (Mabtera® and first domestic biosimilar Acellbia® from Biocad Company. Concentration of protein was measured using Bradford, s method. According to our results, protein concentration in formulations was the same. We electrophoresed formulations in denaturing conditions. Protein from formulations was denatured into fragments. Heavy and light chains of immunoglobulin were observed in gel. Finally, we performed flow cytometry where rituximab was used as primary antibody to detect CD20-positive B-cells of patients with B-cell chronic lymphocytic leukemia. Both Mabtera® and Acellbia® recognized the same number of cells. Thus, assays performed in vitro submitted identity of Mabtera® and Acellbia® characteristics.

  1. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20(+) Indolent B-Cell Non-Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Sehn, L. H.; Goy, A.; Offner, F. C.

    2015-01-01

    Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab...... therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m(2)). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab...... maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab...

  2. CD20单抗临床应用局限与免疫效应器耗竭的研究进展%Limitations of CD20mAb in clinical applications and effectors exhausting

    Institute of Scientific and Technical Information of China (English)

    温良鹤; 徐玉清

    2011-01-01

    CD20单克隆抗体(Rituximab),已被批准应用于非霍奇金B淋巴瘤的治疗,并取得了显著的免疫疗效.但在大负荷循环B细胞存在的情况下,由于机体效应器如效应细胞,效应因子的耗竭,继发表面抗原抗体结合物的削片反应,导致了肿瘤的耐药与复发,降低了Rituximab的疗效.此综述通过对近20年来CD20单抗研究现状的阐述,讨论其作用机制及在效应器耗竭方面的局限,探索适宜的改进方法,以拓展其应用前景.%Rituximab, an approved CD20 monoclonal antibody (CD20mAb), has prominent effects in B-cell non-Hodgkin's lymphoma (NHL). However, the presence of resistance and relapse under high circulatory target B cells burden makes it inefficacious, which may result from antigen antibody complex shaving action based on effectors exhausting, such as effect cells and cytokine. In this review, we expound the research of Rituximab's immunotherapy mechanisms and effectors exhausting in the last two decades, trying to explore eligible strategies to expand its application in the future.

  3. Analyses of CD20 Monoclonal Antibody–Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies

    Science.gov (United States)

    Lindorfer, Margaret A.

    2014-01-01

    Since approval of rituximab for treatment of B cell non-Hodgkin lymphoma, development of monoclonal antibodies (mAbs) for cancer treatment and elucidation of their cytotoxic mechanisms have been subject to intense investigations. Compelling evidence indicates that rituximab and another CD20 mAb, ofatumumab, must use the body’s cellular and humoral immune effector functions to kill malignant cells. Other U.S. Food and Drug Administration–approved mAbs, including obinutuzumab, cetuximab, and trastuzumab, require, in part, these effector mechanisms to eliminate tumor cells. Although gram quantities of mAbs can be administered to patients, our investigations of CD20 mAb-based therapies for chronic lymphocytic leukemia (CLL), including correlative measurements in clinical trials and studies with primary cells and cell lines, indicate that effector mechanisms necessary for mAb activity can be saturated or exhausted if tumor burdens are high, thus substantially compromising the efficacy of high-dose mAb therapy. Under these conditions, another reaction (trogocytosis) predominates in which bound CD20 mAb and CD20 are removed from targeted cells by effector cells that express Fcγ receptors, thereby allowing malignant cells to escape unharmed and continue to promote disease pathology. To address this problem, we propose that a low-dose strategy, based on administering 30–50 mg of CD20 mAb three times per week, may be far more effective for CLL than standard dosing because it will minimize effector function saturation and reduce trogocytosis. This approach may have general applicability to other mAbs that use immune effector functions, and could be formulated into a subcutaneous treatment strategy that would be more accessible and possibly more efficacious for patients. PMID:24944188

  4. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides; Estudo de conjugacao do anticorpo anti-CD20 para marcacao com radionuclideos metalicos ou lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Akanji, Akinkunmi Ganiyu

    2012-07-01

    Lymphomas are malignancies or cancers that start from the malign transformation of a lymphocyte in the lymphatic system. Generally, lymphomas start from the lymph nodes or from the agglomeration of the lymphatic tissues, organs like stomach, intestines, in some cases it can involve the bone marrow and the blood, it can also disseminate to other organs. Lymphomas are divided in two major categories: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Patient with NHL are generally treated with radiotherapy alone or combined with immunotherapy using monoclonal antibody rituximab (MabThera Registered-Sign ). Currently, monoclonal antibodies (Acm) conjugated with bifunctional chelate agents and radiolabeled with metallic or lanthanides radionuclides are a treatment reality for patients with NHL by the principle of radioimmunotherapy (RIT). This study focused on the conditions of conjugation of Acm rituximab (MabThera Registered-Sign ) with bifunctional chelating agents DOTA and DTPA. Various parameters were studied: method of Acm purification, conditions of Acm conjugation, the method for determination of number of chelate agent coupled to the Acm, method for purification of the conjugated antibody Acm, conditions of labeling of the conjugated antibody with lutetium-177, method of purification of the radiolabeled immuno conjugate, method of radiochemical purity (RP), specific binding in vitro Raji cells (Human Burkitt) and biological distribution performed in normal Balb-c mouse. The three methodologies employed in pre-purification of Acm (dialysis, size exclusion chromatograph and dial filtration) demonstrated to be efficient; they provided sample recovery exceeding 90%. However, the methodology of dial filtration presents minimal sample loss, and gave the final recovery of the sample in micro liters; thereby facilitating sample use in subsequent experiments. Numbers of chelators attached to the Acm molecule was proportional to the molar ratio studied. When we evaluated the influence of different conditions of conjugation in the number of chelators bounded to the Acm, no notable differences were observed. The RP < 80% was observed in all the methods applied. Purification of the conjugated antibody by dialysis and size exclusion chromatography demonstrated to be efficient, but deficient in terms of high sample volume recovered. The dial filtration was efficient and practical besides it provided sample recovery in micro liters. The optimized conditions for purification of the conjugated antibody preserved the protein integrity. When the conjugated Acm was labeled with lutetium-177 a product with low RP was observed in all molar ratios studied. The methodology used in the control of RP of the radiolabeled antibody was efficient in the discrimination of radiochemical species presented in the reaction mixture. The method of purification of the conjugated antibody applied, proved to be efficient in separating the labeled antibody from free lutetium. The results of specific cell binding studies performed with the conjugated Acm showed high percentage of nonspecific binding. Biological distribution in normal Balb-c mice demonstrated higher uptake of the labeled antibody by kidney and liver. The relatively high uptake observed by bone tissue may indicate some in vivo instability. However, results obtained in this study showed to be close related in literature. Thus, these data confirm the potential of antibody conjugated to DOTA and DTPA labeled with lutetium-177 for radioimmunotherapy of non-Hodgkin lymphoma. (author)

  5. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  6. 基于AFM单分子力谱技术的CD20-Rituximab间相互作用力测量

    Institute of Scientific and Technical Information of China (English)

    李密; 刘连庆; 席宁; 王越超; 董再励; 李广勇; 肖秀斌; 张伟京

    2011-01-01

    原子力显微镜(AFM)的发明为测量分子间特异性相互作用力提供了新的技术手段.利用AFM单分子力谱(SMFS)技术分别测量了提纯的CD20,淋巴瘤Raji细胞表面的CD20和淋巴瘤病人B细胞表面的CD20与Rituximab(抗CD20单克隆抗体)之间的相互作用力.通过探针功能化技术,将Rituximab连接到AFM针尖;通过基底功能化技术,将提纯的CD20分子吸附到云母表面,对CD20分子进行了AFM成像,并测量了CD20与Rituximab之间的相互作用力;通过静电吸附和化学固定,将淋巴瘤Raji细胞和淋巴瘤病人细胞固定到载玻片表面,对Raji细胞和病人细胞进行了AFM成像,并分别测量了Raji细胞表面的CD20和病人B细胞表面的CD20与Rituximab之间的相互作用力.比较并分析了在提纯的CD20分子表面、Raji细胞表面和病人B细胞表面测量CD20-Rituximab相互作用力的差异,实验结果表明Raji细胞表面的CD20与Rituximab之间的相互作用力明显小于提纯的CD20以及淋巴瘤病人B细胞表面的CD20与Rituximab之间的相互作用力,为深入研究造成Rituximab耐药性差异的分子机理提供了技术思路和实验方法.

  7. Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.

    Science.gov (United States)

    Awasthi, Aradhana; Ayello, Janet; Van de Ven, Carmella; Elmacken, Mona; Sabulski, Anthony; Barth, Matthew J; Czuczman, Myron S; Islam, Humayun; Klein, Christian; Cairo, Mitchell S

    2015-12-01

    Obinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma (BL) and 40% with precursor B-cell acute lymphoblastic leukaemia (pre-B-ALL). We evaluated the anti-tumour activity of obinutuzumab versus rituximab against rituximab-resistant (Raji 4RH) and -sensitive (Raji) BL and pre-B-ALL (U698-M) cells in vitro and in human BL or Pre-B-ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, (P = 0·001), Raji4RH 19·7 ± 2·2% vs. 7·9 ± 1·5% (P = 0·001) and U-698-M 47·3 ± 4·9% vs. 23·2 ± 0·5% (P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% (P = 0·001), Raji-4RH 40·0 ± 1·6% vs. 0·5 ± 1·1% (P = 0·001) and U-698-M 70·0 ± 1·6% vs. 45·5 ± 0·1% (P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL; Raji (P = 0·05), Raji4RH (P = 0·02) and U698-M (P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab-sensitive/-resistant BL and pre-B-ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD20(+) BL and/or pre-B-ALL.

  8. Loss of CD20 expression in relapsed diffuse large B cell lymphoma after rituximab therapy: a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Yao Jiang; Yingchao Zhao; Xiaorong Dong; Sheng Zhang; Yan Li; Gang Wu

    2013-01-01

    Nowadays, resistance to rituximab has become a major issue in clinical practice. And loss of CD20 may contribute to it. Here we presented a case of loss of CD20 expression in relapsed diffuse large B cell lymphoma treated with rituximab and discuss the incidence, mechanism, influence factors, specific markers, prognosis and treatment of this disease. These results suggested that a post-relapse biopsy after rituximab treatment should be performed. CD79a and Pax-5 should be used as the first-line B lineage-specific markers for these patients. Though mechanisms of CD20 decrement are not fully elucidated, the down-regulation of CD20 mRNA is the most probable hypothesis. Recently various new agents are developed, but the prognosis is still poor. Further studies for new treatments are needed.

  9. CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: A matched case-control analysis in a single institution

    Directory of Open Access Journals (Sweden)

    Li Ya-Jun

    2012-05-01

    Full Text Available Abstract Background HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21 were reviewed. Then, a matched case-control (1:3 analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3% CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB subtype. High Ki67 expression (≥80%, an index of cell proliferation, was demonstrated in 17 of 24 (70.8% cases. Extranodal involvement (≥ 1 site was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9% cases achieved complete remission, 4 (19% achieved partial remission, 1 (4.8% had stable disease, and 7 (33.3% had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS and overall survival (OS rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement, whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008 and OS (P = 0.008 rates of 52% and 74.1%, respectively. Conclusions This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer

  10. Humax-CD20治疗非何杰金氏淋巴瘤的Ⅲ期试验开始

    Institute of Scientific and Technical Information of China (English)

    贾永蕊(摘)

    2007-01-01

    Genmab公司已经开始其全人抗CD20单克隆抗体Humax-CD20(ofatumumab)(Ⅰ)治疗滤泡型非何杰金氏淋巴瘤的Ⅲ期试验。该试验选录了162例病人,他们用Roche/Genentech/Biogen Idec公司的Mabthera/Rituxan(rituximab)联合化疗或者将rituximab作为维持治疗的效果不佳。

  11. Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody.

    Science.gov (United States)

    Goede, Valentin; Klein, Christian; Stilgenbauer, Stephan

    2015-01-01

    Obinutuzumab (GA101) is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. Preclinical data demonstrated more efficient B-cell depletion in whole blood and superior antitumor activity in xenograft models of obinutuzumab as compared to the type I CD20 antibody rituximab. In previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities, obinutuzumab plus chlorambucil increased response rates and prolonged progression-free survival compared with rituximab plus chlorambucil. Obinutuzumab had an acceptable and manageable safety profile, with infusion-related reactions during the first infusion as the most common adverse event. Further phase I/II clinical trials have also shown promising activity in other CD20-positive B-cell non-Hodgkin's lymphomas (NHL). Therefore, several clinical studies are planned or ongoing to investigate obinutuzumab with different combination partners in both untreated and relapsed/refractory patients with different B-cell NHL entities, which in addition to CLL include diffuse large B-cell lymphoma and follicular lymphoma. © 2015 S. Karger GmbH, Freiburg.

  12. 利用AFM探测淋巴瘤细胞表面CD20抗原与其抗体的相互作用

    Institute of Scientific and Technical Information of China (English)

    李密; 刘连庆; 席宁; 王越超; 董再励; 李广勇; 肖秀斌; 张伟京

    2010-01-01

    在分子水平阐明细胞生理活动深层次的机制是当前生命科学的重要研究课题.AFM的发明为揭示细胞生理活动的分子本质提供了新的技术手段.利用AFM单分子力谱技术在近生理环境下对B淋巴瘤细胞表面的CD20抗原与其抗体Rituximab之间的特异性结合反应进行了探索性的研究,通过对探针进行功能化,测量了CD20抗原与Rituximab之间的特异性结合力,同时观察了CD20抗原在B淋巴瘤细胞表面的分布,并分析了在外部拉力作用下,CD20-Rituximab复合物的分子内力与伸长量的关系.实验结果为深入研究Rituximab的作用机制奠定了基础.

  13. Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

    Directory of Open Access Journals (Sweden)

    Dayana Santos Mendes

    2013-02-01

    Full Text Available Disseminated leishmaniasis (DL differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics. Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

  14. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: A prospective randomized HOVON trial

    NARCIS (Netherlands)

    E. Vellenga (Edo); W.L.J. van Putten (Wim); M.B. van 't Veer (Mars); J.M. Zijlstra (Josée); W.E. Fibbe (Willem); M.H.J. van Oers (Marinus); L.F. Verdonck (Leo); P.W. Wijermans (Pierre); G. van Imhoff (Gustaaf); P.J. Lugtenburg (Pieternella); P.C. Huijgens (Peter)

    2008-01-01

    textabstractWe evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine- dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-

  15. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20(+) NHL : a prospective randomized HOVON trial

    NARCIS (Netherlands)

    Vellenga, Edo; van Putten, Wim L. J.; van't Veer, Mars B.; Zijlstra, Josee M.; Fibbe, Willem E.; van Oers, Marinus H. J.; Verdonck, Leo F.; Wijermans, Pierre W.; van Imhoff, Gustaaf W.; Lugtenburg, Pieternella J.; Huijgens, Peter C.

    2008-01-01

    We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20(+) non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine

  16. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.

    Science.gov (United States)

    Herter, Sylvia; Herting, Frank; Mundigl, Olaf; Waldhauer, Inja; Weinzierl, Tina; Fauti, Tanja; Muth, Gunter; Ziegler-Landesberger, Doris; Van Puijenbroek, Erwin; Lang, Sabine; Duong, Minh Ngoc; Reslan, Lina; Gerdes, Christian A; Friess, Thomas; Baer, Ute; Burtscher, Helmut; Weidner, Michael; Dumontet, Charles; Umana, Pablo; Niederfellner, Gerhard; Bacac, Marina; Klein, Christian

    2013-10-01

    We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation.

  17. CD20单克隆抗体rituximab在B淋巴细胞疾病靶向治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    钱军; 林江

    2002-01-01

    CD20是前B淋巴细胞向成熟淋巴细胞分化过程中表达的表面抗原.除了在正常B淋巴细胞分化过程中表达外,CD20也在许多B细胞性恶性肿瘤如淋巴瘤、慢性淋巴细胞白血病、多发性骨髓瘤以及Waldenstrom巨球蛋白血症中表达,为B细胞恶性肿瘤的特异性靶向治疗提供了较为理想的靶点.本文介绍近年来rituximab在B淋巴细胞性疾病中的临床应用概况.

  18. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

  19. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...

  20. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K;

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...... reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B cell-depleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy....

  1. Development of [{sup 62}Zn/{sup 62}Cu]-DOTA-rituximab as a possible novel in vivo PET generator for anti-CD20 antigen imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gholipour, Nazila [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Moradkhani, Sedigheh; Bolourinovin, Fateme [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Sabzevari, Omid [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Toxicology and Pharmacology; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Medical Chemistry

    2014-07-01

    In this study, zinc-62 was prepared at radiopharmaceutical grade (for {sup 62}Zn/{sup 62}Cu generator production) using {sup nat}Cu(p, xn) reaction with the production yield of 5.9 mCi/μAh at 30 MeV proton energy (radiochemical separation yield >95%, radionuclidic purity >99% and radiochemical purity >99%). In the next step, rituximab was successively labeled with [{sup 62}Zn]-ZnCl{sub 2} after conjugation with p-SCN-Bz-DOTA followed by molecular filtration and determination of the average number of DOTA conjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (>97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of [{sup 62}Zn]-DOTA-rituximab (in final formulation, and human serum) were determined 1-8 h as well as biodistribution studies in wild-type rats followed by coincidence imaging for 6 h. However, the accumulation of the radiolabeled antibody was not consistent with the former reported rituximab conjugates. [{sup 62}Zn]-labeled monoclonal antibodies and fragments can be prepared as potential in vivo PET generators for molecular imaging however, the search for application of stable zinc complexes must be continued.

  2. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    OBJECTIVES: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  3. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    Science.gov (United States)

    Mendoza-Pinto, Claudia; Garcia-Carrasco, Mario; Vallejo-Ruiz, Veronica; Taboada-Cole, Alejandro; Muñoz-Guarneros, Margarita; Solis-Poblano, Juan Carlos; Pezzat-Said, Elias; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis Felipe; de Lara, Luis Vazquez; Ramos-Alvarez, Gloria; Reyes-Leyva, Julio; Lopez-Colombo, Aurelio

    2013-01-01

    OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus. PMID:24473503

  4. Bone marrow dosimetry using blood-based models for {sup 131}i-anti-cd20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, J. H.; Kim, H. G.; Choi, T. H. [Korea Cancer Center Hospital, Seoul (Korea, Republic of)] (and others)

    2005-07-01

    Accurate estimations of radiation absorbed dose are essential part of evaluating the risks and benefits associated with radiotherapy. Determination of red marrow dose is important because myelotoxicity is often dose limiting in radioimmunotherapy. The aim of this study is to set up the procedures of dosimetry with activities in the blood and whole-body and to estimate the dose of patients according to MIRD schema. Therapy activities of 131I (136, 185, 200 mCi) were administrated to patients (n=3). Blood activity concentrations and whole-body images by gamma camera were collected from patients with non-Hodgkin's lymphoma (5min, 6h, 24h, 48h, 72h, 2week). Two kinds of patient specific approaches based on Sgouros bone marrow dosimetry methodology were considered to estimate bone marrow dose. The mean effective half-life in blood and whole-body were 25.2h and 27.1h respectively and the mean absorbed dose to bone marrow was 0.48Gy (0.22{approx}0.93Gy). The dominant contribution of dose was found to be from bone marrow self-dose (over 60%). The procedures of dosimetry with blood and gamma camera image were established. These enable to estimate the radioimmunotherapy patient's dose retrospectively. Some parts of the procedures need to be elaborated to obtain more accurate dose in the near future.

  5. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Claudia Mendoza-Pinto

    2013-12-01

    Full Text Available OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05, and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01 and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005 compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03. In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.

  6. MS4a4B, a CD20 homologue in T cells, inhibits T cell propagation by modulation of cell cycle.

    Directory of Open Access Journals (Sweden)

    Hui Xu

    Full Text Available MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cells.

  7. CD20+ B Cell Depletion in Systemic Autoimmune Diseases: Common Mechanism of Inhibition or Disease-Specific Effect on Humoral Immunity?

    Directory of Open Access Journals (Sweden)

    Panagiotis Pateinakis

    2014-01-01

    Full Text Available Autoimmunity remains a complex physiologic deviation, enabled and perpetuated by a variety of interplayers and pathways. Simplistic approaches, targeting either isolated end-effectors of more centrally placed interactors of these mechanisms, are continuously tried in an effort to comprehend and halt cascades with potential disabling and deleterious effects in the affected individuals. This review focuses on theoretical and clinically proved effects of rituximab-induced CD20+ B cell depletion on different systemic autoimmune diseases and extrapolates on pathogenetic mechanisms that may account for different interindividual or interdisease responses.

  8. CD20单克隆抗体在儿童B细胞恶性淋巴瘤中的应用

    Institute of Scientific and Technical Information of China (English)

    宋华; 石淑文; 徐卫群; 汤永民; 杨世隆; 沈红强

    2002-01-01

    @@ Rituximab(美罗华)为抗CD20的单克隆抗体.以Rituximab为单一制剂治疗低度/滤泡型非霍奇金淋巴瘤(NHL)取得了良好效果.但国内外均未见Rituximab在儿童中应用的报道.我们对4例儿童B细胞NHL应用Rituximab进行治疗,以了解儿童对Rituximab治疗的耐受性及治疗的副作用,现报告如下.

  9. Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

    DEFF Research Database (Denmark)

    Natarajan, Arutselvan; Gowrishankar, Gayatri; Nielsen, Carsten Haagen

    2012-01-01

    TM, n¿=¿6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. RESULTS: PETRIT was obtained with a specific activity of 545.......86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8¿±¿0.4 µSv/MBq and the spleen at 99¿±¿4 µSv/MBq, respectively. CONCLUSIONS: PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non......PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed...

  10. Identification and characterization of L985P, a CD20 related family member over-expressed in small cell lung carcinoma.

    Science.gov (United States)

    Bangur, Chaitanya S; Johnson, Jeffrey C; Switzer, Ann; Wang, Yi-Hong; Hill, Beth; Fanger, Gary R; Wang, Tongtong; Retter, Marc W

    2004-12-01

    We recently reported on the use of cDNA subtraction combined with microarray based expression analysis for identifying genes that are differentially over-expressed in small cell lung carcinoma. One of the several hundred genes identified using this approach was termed L985P and its molecular characterization is described in this report. The differential over-expression of L985P mRNA in SCLC, as determined by microarray analysis, was confirmed by real-time RT-PCR and Northern blot analysis. Immunohistochemical analyses show that L985P protein is highly expressed in SCLC with very restricted expression observed in normal lung, which was confined to the apical region of the ciliated bronchiolar epithelium. Flow cytometric and immunohistochemical analysis showed that L985P was localized to the cell surface. Sequence homology comparison indicated that L985P is identical to MS4A8B, a member of the recently described membrane-spanning 4-domain family, subfamily A (MS4A) gene family. The MS4A gene family currently consists of greater than 20 distinct human and mouse proteins that include CD20 and FcepsilonRIbeta. Both CD20 and FcepsilonRIbeta are involved in signaling events that regulate diverse cellular functions including cell growth regulation and differentiation. Collectively, the results presented herein demonstrate that L985P is differentially over-expressed in SCLC and may have potential clinical utility as an immunotherapeutic target for the treatment of SCLC.

  11. Influência do CD 20 na refratariedade do linfoma de Hodgkin clássico ao tratamento inicial com o esquema ABVD, no Ceará, Brasil Influence of CD 20 antigen expression in the refractoriness of classical Hodgkin lymphoma in the first line treatment with ABVD protocol in Ceará state, Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Pinto Giesta

    2009-06-01

    Full Text Available INTRODUÇÃO: A significância prognóstica do marcador imunológico CD 20 no linfoma de Hodgkin clássico (LHc ainda é incerta, particularmente no que se refere à refratariedade ao tratamento inicial. OBJETIVOS: Avaliar a influência da positividade do marcador CD 20 na refratariedade do LHc ao tratamento poliquimioterápico inicial, com o esquema doxorubicina 25 mg/m², bleomicina 10 mg/m², vinblastina 6 mg/m² e dacarbazina 375 mg/m² (ABVD, no Ceará, Brasil. MATERIAL E MÉTODOS: Estudo analítico incluindo 97 pacientes com diagnóstico de LHc firmado entre janeiro de 2000 e dezembro de 2004. A análise foi realizada avaliando variáveis demográficas, clínicas e laboratoriais. RESULTADOS: Foi evidenciada uma positividade do CD 20 em 38,1% dos pacientes. Na análise bivariada, CD 20 positivo (razão de chance [RC] = 4,02; intervalo de confiança [IC] = 1,09 - 8,54; p = 0,02, a presença de sintomas B (RC = 4,02; IC = 1,18-17,51; p = 0,01 e a elevação da desidrogenase lática (mediana não-refratários 248,5 [200,5 - 389,5]; mediana refratários 356 [208,5 - 545]; p = 0,03 apresentaram relação de pior prognóstico quanto à refratariedade. Na regressão logística, o CD 20 positivo (RC ajustada = 3,6; IC = 0,99 - 13,09; p = 0,05 e a presença de sintomas B (RC ajustada = 5,41; IC = 1,16 - 25,34; p = 0,03 continuaram apresentando pior prognóstico. DISCUSSÃO: Esses dados coincidem com a literatura, em que a positividade do marcador CD 20 está relacionada com pior resposta ao tratamento com ABVD. CONCLUSÃO: Os nossos dados indicam que o tratamento com ABVD não é completamente adequado para a abordagem terapêutica inicial deste subgrupo de pacientes e novas pesquisas precisam ser realizadas no sentido de aperfeiçoar o tratamento destes pacientes.INTRODUCTION: The prognostic value of CD20 antigen expression in classical Hodgkin lymphoma (cHL is uncertain, particularly regarding the refractoriness to first-line treatment. OBJECTIVES

  12. Synthesis and Evaluation of Cy7-Rituximab Targeting CD20 Antigen for in vivo Animal Fluorescence Imaging%CD20靶向Cy7-Rituximab分子探针的制备及在小鼠活体荧光成像中的应用

    Institute of Scientific and Technical Information of China (English)

    林新峰; 朱华; 洪业; 杨志

    2013-01-01

    以B淋巴细胞表面CD20抗原靶向的单克隆抗体Rituximab为载体,通过共价键偶联荧光基团菁染料Cy7,获得了新型荧光分子探针Cy7-Rituximab.利用全光谱紫外-可见分光光度仪、SDS-聚丙烯酰胺凝胶电泳和基质辅助激光解析电离飞行时间质谱等对该探针结构进行表征,并通过激光共聚焦显微镜观察了其在弥漫大B细胞淋巴瘤(DLBCL)细胞中的摄取情况.选用BALB/C裸鼠为模型,尾静脉注射Cy7-Rituximab,通过活体荧光成像系统观察了其在小鼠体内的分布情况.研究结果表明,修饰后的Cy7-Rituximab保持了原有抗体的免疫活性.活体荧光成像结果表明,在CD20高表达的脾脏部位监测到该分子探针的特异性浓集.

  13. 131Ⅰ标记抗CD20单克隆抗体不同给药途径对荷瘤裸鼠的放射免疫治疗实验%Experimental Research on Radioimmunotherapy of 131Ⅰ-labeled Anti-CD20 Monoclonal Antibody to Nude Mice Xenografted Tumor

    Institute of Scientific and Technical Information of China (English)

    左强; 罗宇玲; 罗荣城

    2011-01-01

    Objective To investigate the therapeutic efficacy of radioimmunotherapy of iodine-131 labeled Rituximab using intratumor injection(IT)in nude mice with xenografted raji cells tumor. Methods Iodine-131 labeled Rituximab was carried out by IODO-GEN method. The nude mice bearing raji cells tumor were divided into six groups based on the injected marked-drugs. The size of the tumor was measured every 2~3 day and the inhibition rates of different groups were calculated. Results The tumor inhibition rates of 131 I-Rituximab IT group were higher than those of IP group, 131 I-IgG IT group and cell control group(P<0. 05). 131 I-Rituximab with intratumor injection in different dose showed that inhibition rate of low dose group was lower than that of high group, while there was no significant difference(P>0. 05). Conclusion lodine-131 labeled Rituximab with intratumor injection showed the highest radioimmunotherapy efficacy which offered the experimental evidence for clinical application in the futrue.%目的 探讨131Ⅰ-Rituximab经瘤内注射对荷人Burkitt's淋巴瘤细胞系Raji细胞移植瘤裸鼠放射免疫治疗疗效.方法 131Ⅰ标记物的标记采用IODO-GEN碘化标记;按预定治疗方案分别注入含有131Ⅰ标记物,开始治疗前及治疗后每天用游标卡尺测量肿瘤长、短径,计算肿瘤体积,依公式计算肿瘤生长抑制率.结果 131Ⅰ-Rituximab瘤内注射组肿瘤抑制率显著高于腹腔注射组、131Ⅰ-IgG瘤内注射组以及对照细胞组(P0.05).结论 131Ⅰ-Rituximab经瘤内途径给药可以获得更好的放射免疫治疗效果,为下一步临床应用奠定了基础.

  14. CD20-negative DLBCL transformation after rituximab treatment in follicular small cleaved cell lymphoma-a clinicopathological analysis and review of the literature%滤泡型小裂细胞性淋巴瘤利妥昔单抗治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤临床病理分析并文献复习

    Institute of Scientific and Technical Information of China (English)

    杨翔; 张瑗; 吴宁; 刘瑜; 王璇; 吴楠; 周晓军; 万文辉

    2016-01-01

    目的:探讨B细胞恶性肿瘤美罗华(rituximab)治疗后复发伴CD20抗原表达丢失患者的临床病理学特征、免疫学表型、治疗及预后。方法:回顾性分析1例滤泡型小裂细胞性淋巴瘤患者经美罗华治疗后转变为CD20阴性的弥漫大B细胞淋巴瘤的临床病理资料,并结合相关文献进行复习。结果:患者于1987年以左侧腮腺区淋巴结肿大为首发症状,1988年行左侧腮腺区淋巴结活检诊断为滤泡型小裂细胞性淋巴瘤,先后进行了50个疗程的“COP、OP”方案化疗及短期局部放疗。1998年出现白细胞升高及淋巴细胞百分数升高,骨髓穿刺诊断为慢性淋巴细胞白血病。2012年3月至2014年3月因白细胞急剧增高多次使用“美罗华”治疗,2014年3月患者出现咽喉部不适,行会厌部取检,诊断为右侧舌根部CD20阴性的弥漫大B细胞淋巴瘤,经过3个疗程的“mini-CHOP”治疗及2次“美罗华”治疗后右侧会厌部肿块消失,2015年5月再次出现右侧颈部淋巴结肿大,经活检诊断为CD20阳性的弥漫大B细胞淋巴瘤。结论:美罗华治疗恶性B细胞淋巴瘤后CD20抗原表达丢失在临床中并非罕见,建议临床中对于美罗华治疗复发或不敏感的病例重新取组织活检进行病理诊断、免疫标记,必要时进行分子遗传学检测,以免误诊,并可对复发病因的药物调整起到的积极指导作用。%Objective: To investigate the clinicopathological features, immunological phenotype, treatment and prognosis of relapsed B-cell malignancies with loss of CD20 immunoreactivity atfer rituximab therapy.Methods: A retrospective analysis of one case of follicular small cleaved cell lymphoma which transformed to CD20-negative DLBCL after rituximab treatment was conducted. We reviewed and analyzed the clinicopathological features, immunological phenotype, treatment and prognosis of the patients.Results: We describe an 87-year

  15. [Safety and efficacy of biologics directed against TNF-alpha and CD20 in the therapy of vasculitis and systemic lupus erythematosus].

    Science.gov (United States)

    Walker, Ulrich A; Hasler, Paul

    2008-05-01

    While the inhibition of TNF-alpha has been shown to improve vasculitis in vitro and in animal models, the clinical evidence for the efficacy of TNF-alpha blockade in most forms of vasculitis is mainly based on case reports and case series. Randomised controlled studies have so far not shown superiority of anti-TNF-alpha agents for Wegener's granulomatosis and giant cell arteritis. Moreover, in the context of Wegener's granulomatosis, a higher frequency and severity of infections are to be expected. In refractory cases of Behçet's disease therapy of uveitis and other organ manifestations is promising. Rituximab has achieved good effects in case reports of vasculitis. Results from controlled trials are not available. Observational studies indicate that in refractory systemic lupus erythematosus, and possibly also in several instances of small vessel vasculitis, rituximab can achieve good responses. The increased frequency of severe infections under TNF-alpha blockade requires a stringent benefit and risk assessment in addition to a multidisciplinary analysis of follow-up parameters. A detailed information of the patient regarding symptoms and signs of a possible infection are a prerequisite. Due to the complexity of the field and the danger of morbidity and mortality as a consequence of vasculitis or systemic lupus erythematosus on the one hand, and of the therapy on the other, biologics should only be used to treat these disorders in institutions fully equipped and staffed for this purpose.

  16. Tumour targeting and radiation dose of radioimmunotherapy with {sup 90}Y-rituximab in CD20+ B-cell lymphoma as predicted by {sup 89}Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Muylle, Kristoff [Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium); Universite Libre de Bruxelles, Department of Nuclear Medicine, Jules Bordet Institute, Brussels (Belgium); Flamen, Patrick; Guiot, Thomas; Ghanem, Ghanem; Meuleman, Nathalie; Bourgeois, Pierre; Vanderlinden, Bruno; Vaes, Melanie; Bron, Dominique [Universite Libre de Bruxelles, Jules Bordet Institute, Brussels (Belgium); Vugts, Danielle J.; Dongen, Guus A.M.S. van [VU University Medical Centre, Amsterdam (Netherlands); Everaert, Hendrik [Vrije Universiteit Brussel, UZ Brussel, Brussels (Belgium); Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium)

    2015-07-15

    To compare using immuno-PET/CT the distribution of {sup 89}Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with {sup 90}Y-labelled rituximab in CD20+ B-cell lymphoma. Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline {sup 89}Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m{sup 2}) of unlabelled rituximab followed by injection of {sup 89}Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by {sup 90}Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. With a cold rituximab preload, the calculated whole-body dose of {sup 90}Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the ''prerituximab era''. (orig.)

  17. A clinical study on the therapeutic effect of rituximab in combination with autologous peripheral blood stem cell transplantation in treatment of CD20+ B cellulous non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    Yong-sheng CHEN

    2013-07-01

    Full Text Available Objective To investigate the therapeutic effect of autologous peripheral blood stem cell transplantation (APBSCT in combination with rituximab in treatment of CD20+ B cellulous non-Hodgkin's lymphoma (B-NHL. Methods Sixty patients with CD20+ aggressive or refractory and recurrent B-NHL and treated with APBSCT in our department from Jan. 2005 to Jan. 2011 were admitted. All the subjects were divided into 2 groups according to their own choice: 25 patients received rituximab treatment (treatment group and 35 patients were treated without rituximab treatment (control group. All patients underwent chemotherapy and APBSCT. For patients in treatment group, rituximab was used with CHOP before collecting the stem cells and after the transplantation. After transplantation, rituximab and IL-2 were used in treatment group every 3-6 months as maintenance treatment. Results No side effect was observed during the use of rituximab either before or after transplantation. The mononuclear cell count in treatment and control group was (8.2±2.9×108/kg and (8.4±3.9×108/kg (P=0.822, respectively; CD34+cell count was (12.3±12.7×106/kg and (13.2±13.9×106/kg (P=0.799, respectively. Haemopoiesis reconstruction was successfully achieved in the patients of treatment group, while 3 patients in control group failed to have haemopoiesis reconstruction. No significant difference was found between two groups on the recovery time of neutrophilic granulocytes and platelets. All patients achieved complete remission. The average follow-up time was 22 months. The disease relapsed in two patients in treatment group and six in control group. The 3-year overall survival rate in treatment group (91.6% was a little higher than that in control group (69.5%, P=0.060. Conclusion To patients of CD20+ B lymphoma, the use of rituximab shows no side effect before or after collection of stem cell and hemopoiesis reconstruction, and the overall survival rate may be improved.

  18. Assessment of absorbed dose and therapeutic response of tumor in repeated high-dose I-131 anti-CD20 monoclonal antibody (rituximab) radioimmunotherapy for non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Sang Moo; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    We assessed the therapeutic dose absorbed to the tumor and response in repeated RIT with I-131 rituximab for NHL. Patients with NHL (n=6) were administered a therapeutic dose of I-131 rituximab (192.527.0 mCi). The number of repeated administration was 3 for all patients. Total 12 measurable tumor regions were assessed at the time of each RIT. Whole-body (WB) planar images with anterior and posterior views were acquired sequentially at 5 min, 5hr, 24hr, 48hr, and 72hr post-injection using gamma camera. F-18-FDG PET/CT was performed before (within 7 days) and after (on Day 30) RIT. From PET/CT image acquired before RIT, maximum intensity projection (MIP) image of coronal view was acquired. Serial WB planar images were overlaid to the coronal MIP PET image, respectively, by means of registration using 4 fiducial marks (bilateral shoulder and buttock) implemented in AMIDE software. On registered MIP PET and WB planar images, both 2D-ROIs were drawn on the region of tumor and background nearby tumor. The shape of 2D-ROI of tumor was determined from the MIP PET image. The volume of tumor was measured from the CT image, the % change of tumor volume before and after RIT was used in evaluation of the therapeutic response. The values of CT-based tumor volume were 8.216.3cc. The values of absorbed dose for tumor and the % changes of tumor volume before and after RIT were 231.8603.0rad, and 55.548.7%, respectively, and did not show the linear relationship (r=0.2787). The values of absorbed dose for tumor and the % changes of tumor volume did not correlate with the number of repeated administration (p>0.05, ANOVA). Aligning PET and planar images could estimate the quantitative values of absorbed dose to tumor. The data suggest that repeated RIT with I-131 rituximab is necessary for NHL, because single-RIT is insufficient to achieve remission of disease.

  19. Image-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose {sup 131}I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Kim, Kyeong Min; Woo, Sang Keun; Choi, Tae Hyun; Kang, Hye Jin; Oh, Dong Hyun; Kim, Byeong Il; Choen, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-02-15

    We assessed the absorbed dose to the tumor (Dose tumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with {sup 131}I rituximab for NHL. Patients with NHL (n=4) were administered a therapeutic dose of {sup 131}I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. The values of absorbed dose were 397.7{+-}646.2cGy (53.0{approx}2853.0cGy). The values of CT-based tumor volume were 11.3{+-}9.1 cc (2.9{approx}34.2cc), and the % changes of tumor volume before and after RIT were -29.8{+-}44.3% (-100.0%{approx}+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

  20. Cell enrichment-free massive ex-vivo expansion of peripheral CD20⁺ B cells via CD40-CD40L signals in non-human primates.

    Science.gov (United States)

    Kim, Jung-Sik; Byun, Nari; Chung, Hyunwoo; Kim, Hyun-Je; Kim, Jong-Min; Chun, Taehoon; Lee, Won-Woo; Park, Chung-Gyu

    2016-04-22

    Non-human primates (NHPs) are valuable as preclinical resources that bridge the gap between basic science and clinical application. B cells from NHPs have been utilized for the development of B-cell targeted drugs and cell-based therapeutic modalities; however, few studies on the ex-vivo expansion of monkey B cells have been reported. In this study, we developed a highly efficient ex-vivo expansion protocol for monkey B cells resulting in 99% purity without the requirement for prior cell-enrichment procedures. To this end, monkey peripheral blood mononuclear cells (PBMCs) were stimulated for 12 days with cells constitutively expressing monkey CD40L in expansion medium optimized for specific and massive expansion of B cells. The B cells expansion rates obtained were 2-5 times higher than those previously reported in humans, with rates ranging from 7.9 to 16.6 fold increase. Moreover, expanded B cells sustained high expression of co-stimulatory molecules including CD83 and CD86 until day 12 of culture, and the simple application of a brief centrifugation resulted in a CD20(+) B cell purity rate of greater than 99%. Furthermore, small amounts of CD3(+)CD20(+)BT-like cells were generated and CD16 was expressed at moderate levels on expanded B cells. Thus, the establishment of this protocol provides a method to produce quantities of homogeneous, mature B cells in numbers sufficient for the in vitro study of B cell immunity as well as for the development of B cell-diagnostic tools and cell-based therapeutic modalities.

  1. 扫描探针显微术用于B淋巴瘤细胞表面分子数量化与可视化研究%Visualization and quantitation of CD20 molecues on human B-cell lymphoma by scanning probe microscopy (SPM)

    Institute of Scientific and Technical Information of China (English)

    王淑蕙; 赵磊; 李华飞; 陈雅琳; 王皓; 郭亚军; 李博华

    2013-01-01

    AFM (atomic force microscopy) and NSOM (near field scanning microscopy) have extremely high resolution and many advantages in exploring the biology.In this work,AFM and NSOM were used to investigate the morphology and ultrastructure of human B-cell lymphoma before and after treatment with CD20 antibody Rituximab,we used AFM combined with NSOM to optically investigate CD20 molecules on human B-cell lymphoma.The location,distribution and variation of CD20 molecules were imaged by a high-resolve NSOM.The results showed that a method that could be used to observe the ultrastructure of surface molecules on B cell lymphoma was established and the distribution of membrane-bound CD20 molecules was observed by the two types of high-resolution microscopies.After treatment with Rituximab,the lymphoma cell surface has small granules,indicating abundant structure infomation inside the cells,and NSOM found that CD20 molecules remained scat tered on the cell surface.%本研究试图采用原子力显微术(AFM)和近场光学显微术(NSOM)对B淋巴瘤细胞的表面形态和超微结构进行了纳米级高分辨的成像研究,获得Rituximab抗体处理前后不同状态下的高清晰、对比度良好的NSOM和AFM的B淋巴瘤细胞图像,建立超高分辨率显微镜观测B淋巴瘤细胞膜分子表面分布的方法.采用AFM和NSOM,对B淋巴瘤细胞的表面形态及光学性质进行了观测.结果显示建立了一种观测B淋巴瘤细胞超微细胞表面结构的方法,结合NSOM对Rituximab抗体处理前后CD20膜蛋白分子在细胞膜表面位置进行高分辨率的观测.AFM的结果表明Rituximab抗体处理以后B淋巴瘤细胞细胞膜的颗粒度明显增加,NSOM结果发现在Rituximab处理B淋巴瘤细胞前后,CD20膜蛋白分子仍然散在分布在细胞膜表面.

  2. Anti-tumor activity of obinutuzumab and rituximab in a follicular lymphoma 3D model.

    Science.gov (United States)

    Decaup, E; Jean, C; Laurent, C; Gravelle, P; Fruchon, S; Capilla, F; Marrot, A; Al Saati, T; Frenois, F-X; Laurent, G; Klein, C; Varoqueaux, N; Savina, A; Fournié, J-J; Bezombes, C

    2013-08-09

    Follicular lymphomas (FLs) account for 35-40% of all adult lymphomas. Treatment typically involves chemotherapy combined with the anti-CD20 monoclonal antibody (MAb) rituximab (RTX). The development of the type II anti-CD20 MAb obinutuzumab (GA101) aims to further improve treatment. Here, using FL cells we show that RTX and GA101 display a similar activity on RL cells cultured in 2D. However, 2D culture cannot mimic tumor spatial organization and conventional 2D models may not reflect the effects of antibodies as they occur in vivo. Thus, we created a non-Hodgkin's lymphoma (NHL) 3D culture system, termed multicellular aggregates of lymphoma cells (MALC), and used it to compare RTX and GA101 activity. Our results show that both antibodies display greater activity towards FL cells in 3D culture compared with 2D culture. Moreover, we observed that in the 3D model GA101 was more effective than RTX both in inhibiting MALC growth through induction of (lysosomal) cell death and senescence and in inhibiting intracellular signaling pathways, such as mammalian target of rapamycin, Akt, PLCgamma (Phospholipase C gamma) and Syk. Altogether, our study demonstrates that spatial organization strongly influences the response to antibody treatment, supporting the use of 3D models for the testing of therapeutic agents in NHL.

  3. High titers of anti-HBs prevent rituximab-related viral reactivation in resolved hepatitis B patient with non-Hodgkin's lymphoma.

    Science.gov (United States)

    Cho, Yuri; Yu, Su Jong; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Tae Min; Heo, Dae Seog; Kim, Yoon Jun; Yoon, Jung-Hwan

    2016-06-01

    Rituximab, an anti-CD20 monoclonal antibody, is associated with an increased risk of hepatitis B virus (HBV) reactivation. This study aimed to determine the predictive factors for rituximab-related HBV reactivation in resolved hepatitis B patients, defined as HBsAg-negative, anti-HBc-positive, and undetectable HBV DNA. Among 840 consecutive patients with CD20-positive B-cell lymphoma who received rituximab-based chemotherapy from 2003 through 2014 at Seoul National University Hospital, 732 patients were excluded because either anti-HBc was not assessed or they were HBsAg-seropositive. This retrospective study included 108 resolved hepatitis B patients. During a median 33.5-month follow-up period, eight cases of HBV reactivation occurred only among the patients with low anti-HBs titers (anti-HBs titers were the protective factors for HBV reactivation (hazard ratio [HR], 0.90 and 0.95, respectively). Among those who did not receive antiviral prophylaxis, patients with high baseline anti-HBs (≥100 mIU/ml) experienced significantly lower risk of HBV reactivation (HR, 0.49; P = 0.006) than the patients with low baseline anti-HBs (anti-HBs titer at baseline and antiviral prophylaxis prevented HBV reactivation, suggesting antiviral prophylaxis should be considered according to baseline anti-HBs titer. Meticulous follow-up for ALT and HBV DNA without antiviral prophylaxis might be possible for the patients with high baseline anti-HBs (≥100 mIU/ml).

  4. Research Progress of Anti-angiogenesis Drugs in the Treatment of Lymphoma

    Institute of Scientific and Technical Information of China (English)

    Feng Jifeng

    2014-01-01

    As the targeted drugs come into being in recent years, such as monoclonal antibody, great achievements have been made for the treatment of malignant lymphoma (ML). Rituximab, a monoclonal antibody against CD20 whose effective rate is up to 85% in the ifrst-line treatment of lymphoma, has become the standard ifrst-line treatment of multiple B cell lymphomas. However, how to improve the therapeutic efficacy of B lymphoma and reduce reoccurrence rate in drug-resistant patients still need to be further studied. And great importance is increasingly attached to the development of new drugs, especially tumor angiogenesis drugs, in which Bevacizumab and Endostatin are studied as the main representative for the treatment of ML. This paper mainly made a review on Current situation and prospects of anti-angiogenesis drugs for the treatment of lymphoma.

  5. Research Progress of Anti-angiogenesis Drugs in the Treatment of Lymphoma

    Directory of Open Access Journals (Sweden)

    Jifeng Feng

    2014-06-01

    Full Text Available As the targeted drugs come into being in recent years, such as monoclonal antibody, great achievements have been made for the treatment of malignant lymphoma (ML. Rituximab, a monoclonal antibody against CD20 whose effective rate is up to 85% in the first-line treatment of lymphoma, has become the standard first-line treatment of multiple B cell lymphomas. However, how to improve the therapeutic efficacy of B lymphoma and reduce reoccurrence rate in drugresistant patients still need to be further studied. And great importance is increasingly attached to the development of new drugs, especially tumor angiogenesis drugs, in which Bevacizumab and Endostatin are studied as the main representative for the treatment of ML. This paper mainly made a review on Current situation and prospects of anti-angiogenesis drugs for the treatment of lymphoma.

  6. Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

    Directory of Open Access Journals (Sweden)

    Lin Xue

    2011-03-01

    Full Text Available Abstract Background The aims of this study were: (1 to show the feasibility of using adipose-derived stromal vascular fraction (SVF as an alternative to bone marrow mono nuclear cell (BM-MNC for cell transplantation into chronic ischemic myocardium; and (2 to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI against left ventricular (LV remodelling and cardiac dysfunction. Methods Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12 had SVF cell transplantation (6 × 106 cells. BM-MNC group (n = 12 received BM-MNCs (6 × 106 and the control (n = 10 had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20. Results At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition. Conclusions Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.

  7. Anti-SIRPα antibodies as a potential new tool for cancer immunotherapy

    Science.gov (United States)

    Yanagita, Tadahiko; Murata, Yoji; Tanaka, Daisuke; Motegi, Sei-ichiro; Arai, Eri; Hazama, Daisuke; Washio, Ken; Saito, Yasuyuki; Kotani, Takenori; Oldenborg, Per-Arne; Ishikawa, Osamu; Kanai, Yae; Komori, Takahide

    2017-01-01

    Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8+ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers. PMID:28097229

  8. Anti-addiction vaccines

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.

    2011-01-01

    Despite intensive efforts to eradicate it, addiction to both legal and illicit drugs continues to be a major worldwide medical and social problem. Anti-addiction vaccines can produce the antibodies to block the effects of these drugs on the brain, and have great potential to ameliorate the morbidity and mortality associated with illicit drug intoxications. This review provides a current overview of anti-addiction vaccines that are under clinical trial and pre-clinical research evaluation. It also outlines the development challenges, ethical concerns, and likely future intervention for anti-addiction vaccines. PMID:22003367

  9. Anti-inflammatory Diets.

    Science.gov (United States)

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology.

  10. Discrete anti-gravity

    Science.gov (United States)

    Noyes, H. Pierre; Starson, Scott

    1991-03-01

    Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces fields with the relativistic Wheeler-Feynman action at a distance, allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will fall up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound.

  11. Discrete anti-gravity

    Energy Technology Data Exchange (ETDEWEB)

    Noyes, H.P. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Starson, S. (STARSON Corp. (USA))

    1991-03-01

    Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces fields'' with the relativistic Wheeler-Feynman action at a distance,'' allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will fall'' up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound. 23 refs.

  12. Anti-Shock Garment

    Science.gov (United States)

    1996-01-01

    Ames Research Center developed a prototype pressure suit for hemophiliac children, based on research of astronauts' physiological responses in microgravity. Zoex Corporation picked up the design and patents and developed an anti-shock garment for paramedic use. Marketed by Dyna Med, the suit reverses the effect of shock on the body's blood distribution by applying counterpressure to the legs and abdomen, returning blood to vital organs and stabilizing body pressure until the patient reaches a hospital. The DMAST (Dyna Med Anti-Shock Trousers) employ lower pressure than other shock garments, and are non-inflatable.

  13. The Anti-Landscape

    DEFF Research Database (Denmark)

    There have always been some uninhabitable places, but in the last century human beings have produced many more of them. These anti-landscapes have proliferated to include the sandy wastes of what was once the Aral Sea, severely polluted irrigated lands, open pit mines, blighted nuclear zones...

  14. SITUASI PATEN OBAT ANTI DIABETES, ANTI HIPERTENSI, ANTI MALARIA DAN ANTI TUBERKULOSIS DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Basundari Sri Utami

    2014-10-01

    Full Text Available AbstrakIndonesia merupakan negara berpenduduk keempat terbanyak setelah Cina, India dan Amerika. Indonesia sedang mengalami transisi epidemiologi, dimana terjadi peningkatan penyakit tidak menular (PTM, sementara penyakit menular (PM seperti malaria, tuberkulosis dan demam dengue prevalensinya masih tinggi. Tingginya morbiditas merupakan lahan yang bagus untuk melaksanakan obat anti PM dan anti PTM yang mendapat paten karena pangsa pasarnya yang sangat luas. Sayangnya potensi pasar yang masih luas ini hanya ditangkap oleh luar negeri. Data dari Direktorat Jendral Hak Kekayaan Intelektual (Ditjen HKI pada tahun 2010 menunjukkan pemohon paten dalam negeri yang mendapatkan persetujuan perlindungan paten (granted hanya 4,6% sedangkan dari luar negeri sebanyak 92,03%. Hal yang sangat ironis bagi Indonesia yang merupakan negara dengan potensi bahan dasar obat alam dan keanekaragaman hayati terbanyak ketiga setelah Brazil dan Cina. Tujuan penelitian ini untuk mengevaluasi situasi paten obat yang terdaftar di Direktorat Paten, Ditjen HKI, Kementerian Hukum dan Hak Asasi Manusia RI dalam 7 tahun terakhir (tahun 2005 sampai 2011 untuk PM (malaria dan tuberkulosis dan PTM (hipertensi dan diabetes. Metode observasional dengan penelusuran dokumen paten dari alamat web instansi terkait. Hasilnya Indonesia hanya mendaftarkan 4,9% dari seluruh paten yang didaftarkan di Dirjen HKI dari tahun 2005 sampai dengan 2011, sebagai berikut untuk obat anti-hipertensi 3,4% dari 89 paten, anti-diabetes hanya 4,8% dari 250 paten, anti malaria 21,1% dari 18 paten anti-tuberkulosis 7,1% dari 14 paten. Sebagian besar paten yang didaftarkan oleh pendaftar Indonesia merupakan paten obat ekstrak herbal atau komposisinya. Kesimpulan dari penelitian ini adalah paten obat untuk PTM dan PM di Indonesia masih didominasi paten luar negeri.Kata Kunci : Situasi paten, obat, Ditjen HKI, IndonesiaAbstractIndonesia is the fourth most populous country after China, India and America. There

  15. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  16. Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

    Science.gov (United States)

    Bhatti, Adnan Bashir; Usman, Muhammad

    2015-11-06

    The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation. Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking. The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it.

  17. Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity

    Science.gov (United States)

    Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

    2015-01-01

    Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency. PMID:26508306

  18. Anti-antimicrobial Peptides

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  19. [Fetomaternal anti-RH3, -4 (anti-E and anti-c) rhesus isoimmunization: a case report].

    Science.gov (United States)

    Farnault, L; Garcia-Meric, P; Cortey, A; Arnaud, F

    2011-02-01

    Hemolytic disease of the newborn caused by maternal isoimmunization has been decreasing over the past 10 years because of prophylactic treatment with anti-RH1 (anti-D) immunoglobulin. Nevertheless, there is an increase in the incidence of both relative and absolute numbers of non-RH1 red-cell maternofetal isoimmunizations, essentially anti-RH4 (anti-c), anti-RH3 (anti-E), and anti-Kell. In 8 to 14% of cases, multispecificity antibodies are present, the most common combination being the association of anti-RH3 and -4. Despite absence of specific prophylactic therapy, anti-RH4 isoimmunization could be as severe as anti-RH1 ; as for anti-RH3, it is usually associated with mild to moderate clinical manifestations. Nevertheless, there are few publications on anti-RH3, -4 maternofetal isoimmunization with a bias toward the most severe cases being reported. We report here a case of nonsevere maternofetal anti-RH3, -4 isoimmunization complicated with severe hyperbilirubinemia and delayed profound anemia. Hyperbilirubinemia was controlled using intensive phototherapy. Although anemia was absent at birth, it appeared progressively with a nadir at 7.8 g/dL at 1-month postnatal age. Blood counts were monitored for 3 months but the patient did not require red blood cell transfusion. This report underlines the need for a prolonged and rigorous pediatric follow-up of children born in the context of maternofetal isoimmunization after the acute neonatal period. Furthermore, it stresses the necessity of DAT testing in all pregnant women, even those who are RH1-positive.

  20. B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Anastasia Meshcheryakova

    Full Text Available Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively, and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as

  1. Mechanisms of action of the anti-VEGF monoclonal antibody bevacizumab on chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Jakub Bogusz

    2013-03-01

    Full Text Available Introduction: Chronic lymphocytic leukemia (CLL remains incurable; therefore searching for new therapeutic strategies in this disease is necessary. An important mechanism of tumor development is neoangiogenesis. A potent antiangiogenic factor, bevacizumab (Avastin, AVA, has been poorly explored in CLL so far. In the current study we assessed cytotoxic activity of AVA alone or in combinations with drugs routinely used in this disease.Matherials and Methods: Cells isolated from 60 CLL patients were treated with AVA alone or in combination with anti-CD20 monoclonal antibody (MoAb, rituximab (RIT, anti-CD52 MoAb, alemtuzumab (ALT, 2-CdA (2-chlorodeoxyadenosine, FA (fludarabine, MAF (mafosfamide or RAPA (rapamycin. Cytotoxicity was assessed by propidium iodide staining. Apoptosis was evaluated using annexin-V and TUNEL assays. Additionally, a drop of mitochondrial potential (DYm as well as expression of apoptosis-regulating proteins Bax, Bak, Bid, Bad, Bcl-2, Mcl-2, XIAP, FLIP, Akt and Bcl-2-A1 were determined by flow cytometry.Results: At the dose of 40 μg/ml, after 48 hours of incubation, AVA induced significant cytotoxicity against CLL cells. The drug triggered apoptosis, with activation of caspase-3 and -9, but not caspase-8, along with a drop of DYm. Incubation with AVA induced significant overexpression of proapoptotic Bak and Bad as well as downregulation of antiapoptotic Mcl-2 and Akt proteins. Combination of AVA with RIT, ALT or RAPA significantly increased cytotoxicity when compared with the effects of single drugs.Discussion: In conclusion, this is the first report showing proapoptotic activity of AVA against CLL cells. Combination of AVA with RIT, ALT or RAPA may be a promising therapeutic strategy, which requires confirmation in further studies.

  2. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  3. [Anti-synthetase syndrome].

    Science.gov (United States)

    Novak, Srdan

    2012-01-01

    Antysynthetase syndrome is considered as a group ofidiopathic inflammatory myositis with charcteristic serologic hallmark--antibodies which recognise the aminoacyl-tRNA synthetasses (ARS). Clinical picture of those patients contains myositis and/or intersticial lung disease (ILD) and/or arthritis and/or fever and/or Raynaud phenomenon and sometimes characteristic look of mechanic's hands. Myositis can be overt, sometimes even absent, while IBP is major cause of morbidity and determines the outcome of the disease. Untill now eight different any-synthetase autoantibodies are recognised, and most frequent are findings of anti-histidyl-tRNa synthetase antibodies. Patients with other ARS autoantibodies usually have severe ILD. Drug of choice are steroids in dosage of 1 mg/kg with immunosupresive agent (azatioprin or methotrexate) while in severe IBP cyclophosphamide is needed. Recently succsesful treatment with rituximab in combination with cyclophosphamide is reported.

  4. Television and Anti-Racism.

    Science.gov (United States)

    Ali, Yasmin

    The "new" anti-racists of the 1980s in contemporary Britain consider racism, particularly against blacks, as both a structural and a white problem. Anti-racist activists, whose attitude is a mirror-image of the political left's general concern about the media--where blacks are in the minority--regard the media, especially television, as…

  5. [Anti-influenza virus agent].

    Science.gov (United States)

    Nakamura, Shigeki; Kohno, Shigeru

    2012-04-01

    The necessity of newly anti-influenza agents is increasing rapidly after the prevalence of pandemic influenza A (H1N1) 2009. In addition to the existing anti-influenza drugs, novel neuraminidase inhibitors such as peramivir (a first intravenous anti-influenza agent) and laninamivir (long acting inhaled anti-influenza agent) can be available. Moreover favipiravir, which shows a novel anti-influenza mechanism acting as RNA polymerase inhibitor, has been developing. These drugs are expected to improve the prognosis of severe cases caused by not only seasonal influenza but pandemic influenza A (H1N1) 2009 virus and H5N1 avian influenza, and also treat oseltamivir-resistant influenza effectively.

  6. Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

    2010-05-28

    The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

  7. Online Anti-Brand Herds

    DEFF Research Database (Denmark)

    Langley, David J.; Tan, Chee-Wee; Worm, Daniël

    the Netherlands, we develop an analytical model to investigate drivers of herd formation, growth, and dissolution. Finally, combining environmental turbulence literature with our empirical findings, we derive a novel typology of online anti-brand herd behaviors, and put forward six propositions to guide theory...... light on the formation, growth, and dissolution of online anti-brand herds. First we expand on the concept of environmental turbulence to advance core properties unique to online herd behavior. Next, based on evidence gathered from 40 online anti-brand herd episodes targeting two prominent firms from...

  8. Penfigoide anti p-200 Anti-p200 pemphigoid

    OpenAIRE

    T Zarowsky

    2011-01-01

    Se efectúa una revisión del penfigoide ampollar anti-P200 desde el punto de vista clínico, histopatológico, inmunológico como su tratamiento y múltiples diagnósticos diferenciales.A review of the anti-P200 pemphigoid from the clinical, histopathological, immunological are updated, as well assess to its treatment and various differentials diagnosis.

  9. Penfigoide anti p-200 Anti-p200 pemphigoid

    Directory of Open Access Journals (Sweden)

    T Zarowsky

    2011-06-01

    Full Text Available Se efectúa una revisión del penfigoide ampollar anti-P200 desde el punto de vista clínico, histopatológico, inmunológico como su tratamiento y múltiples diagnósticos diferenciales.A review of the anti-P200 pemphigoid from the clinical, histopathological, immunological are updated, as well assess to its treatment and various differentials diagnosis.

  10. Phytochemical, anti-oxidant, anti-microbial, antiinflammatory and anti-ulcer properties of Helianthemum lippii

    Directory of Open Access Journals (Sweden)

    Sami G. Alsabr

    2013-07-01

    Full Text Available The medicinal plants have been considered a healthy source of life for all people and the therapeutical properties of the medical plants are very useful in curing range of diseases. The aims of the study are to evaluate the anti-oxidant, antimicrobial, anti-inflammatory and anti-ulcer properties of Helianthemum lippii (MHL methanolic extracts. MHL sampleswere collected in the mountain region of Libya. The antioxidant properties of MHL were evaluated using free radical scavenging assay. Stomach ulcers were induced in rats by ethanol. Pretreatment with ranitidine and MHL samples were performed before the ulcer induction. Gastric mucosal histological changes in rat stomach tissue were evaluated. Antimicrobial efficacy of MHL was also studied against gram-positive bacteria S. aureus, gram-negative bacteria E. coli , and fungal strain C. albicans. The phytochemical screening of MHL showed presence of flavonoids, tannins, saponine and simple phenolic compounds. MHL exhibited a powerful anti-oxidant activity, where 31.17 ± 1.40 µg/ml of extract caused 50% inhibition on 2,2, Diphenyl-1-picryhydrazyl (DPPH scavenging activity in comparison to standard ascorbic acid (15.35 ± 3.2 µg/ml. MHL also showed substantial anti-microbial activity against a strain of gram-positive bacteria, S. aureu, with zone of inhibition (21 mm and MIC (12.25 mg/ml and a fungal strain, C. albicans, with zone of inhibition (20 mm and MIC (6.25 mg/ml compared to ciprofloxacin or amphotericin B. MHL at doses of 250 and 500 mg/kg produced statistical significant anti-inflammatory activity (23.6%, 50% in comparison to aspirin (60%. It further showed significant anti-ulcer activity in doses of 250mg/kg and 500mg/kg with percentage of gastric lesions inhibitions of 48.78% and 76.82%, respectively, in comparison to standard anti-ulcer ranitidine (50 mg/kg, which showed 69.78%. MHL has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at

  11. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune......-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles...

  12. Anti-DNA antibodies in SLE

    Energy Technology Data Exchange (ETDEWEB)

    Voss, E.W.

    1988-01-01

    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  13. The Anti-Doping Movement.

    Science.gov (United States)

    Willick, Stuart E; Miller, Geoffrey D; Eichner, Daniel

    2016-03-01

    Historical reports of doping in sports date as far back as the ancient Greek Olympic Games. The anti-doping community considers doping in sports to be cheating and a violation of the spirit of sport. During the past century, there has been an increasing awareness of the extent of doping in sports and the health risks of doping. In response, the anti-doping movement has endeavored to educate athletes and others about the health risks of doping and promote a level playing field. Doping control is now undertaken in most countries around the world and at most elite sports competitions. As athletes have found new ways to dope, however, the anti-doping community has endeavored to strengthen its educational and deterrence efforts. It is incumbent upon sports medicine professionals to understand the health risks of doping and all doping control processes.

  14. Bayesian anti-sparse coding

    CERN Document Server

    Elvira, Clément; Dobigeon, Nicolas

    2015-01-01

    Sparse representations have proven their efficiency in solving a wide class of inverse problems encountered in signal and image processing. Conversely, enforcing the information to be spread uniformly over representation coefficients exhibits relevant properties in various applications such as digital communications. Anti-sparse regularization can be naturally expressed through an $\\ell_{\\infty}$-norm penalty. This paper derives a probabilistic formulation of such representations. A new probability distribution, referred to as the democratic prior, is first introduced. Its main properties as well as three random variate generators for this distribution are derived. Then this probability distribution is used as a prior to promote anti-sparsity in a Gaussian linear inverse problem, yielding a fully Bayesian formulation of anti-sparse coding. Two Markov chain Monte Carlo (MCMC) algorithms are proposed to generate samples according to the posterior distribution. The first one is a standard Gibbs sampler. The seco...

  15. Anti-G with concomitant anti-C and anti-D: A case report in a pregnant woman

    Directory of Open Access Journals (Sweden)

    Rabeya Yousuf

    2017-01-01

    Full Text Available The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.

  16. Anti-TNF-α biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2012-01-01

    This article discusses the rationale behind recommending immunopharmacological guidance of long-term therapies with genetically engineered anti-TNF-α immunoglobulin constructs. Arguments why therapeutic decision-making should not rely on clinical outcome alone are presented. Central to this is th......This article discusses the rationale behind recommending immunopharmacological guidance of long-term therapies with genetically engineered anti-TNF-α immunoglobulin constructs. Arguments why therapeutic decision-making should not rely on clinical outcome alone are presented. Central....... Large-scale immunopharmacological knowledge of how patients 'handle' TNF-α biopharmaceuticals would also help industry develop more effective and safer TNF-α inhibitors....

  17. Generalized anti-centrifugal potential

    Energy Technology Data Exchange (ETDEWEB)

    Dandoloff, Rossen [Laboratoire de Physique Theorique et Modelisation, Universite de Cergy-Pontoise, F-95302 Cergy-Pontoise (France); Jensen, Bjørn [Department of Micro and Nano Systems Technology, Vestfold University College, N-3103 Tønsberg (Norway); Saxena, Avadh, E-mail: avadh@lanl.gov [Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2014-01-24

    We generalize the quantum anti-centrifugal potential in the two-dimensional Euclidean plane to two-dimensional surfaces embedded in three-dimensional Euclidean space. We consider the sphere with two caps removed in some detail. We show that quantum particles in this space are “pushed” towards either of the cap boundaries. We also consider the two-dimensional Euclidean plane with an elliptic area removed and compute the quantum anti-centrifugal potential on the elliptic boundary. It is argued that a sufficiently thin electrically conducting nano-wire shaped as an ellipse will exhibit an inhomogeneous charge distribution due to this quantum potential.

  18. Selective anti-cancer agents as anti-aging drugs.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-12-01

    Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease.

  19. 狼疮肾炎患者anti-GBM与anti-dsDNA和anti-NuA相关性研究%Anti- GBM and Anti- ds DNA Associated with Anti- NuA in Patients with Lupus Nephritis

    Institute of Scientific and Technical Information of China (English)

    李成海; 张聪恪; 赵静; 邹国林

    2006-01-01

    目的 探讨狼疮肾炎患者抗肾小球基底膜抗体(anti-GBM)与抗双链DNA抗体(anti-ds DNA)和抗核小体抗体(anti-NuA)的关系.方法 反馈分析28例anti-GBM阳性的狼疮肾炎患者致肾炎抗体间的关系.结果 28例anti-GBM阳性的狼疮性肾炎患者有13例anti-ds DNA阳性和17例anti-NuA阳性.并且,血清anti-GBM的水平与anti-ds DNA和/或anti-NuA水平一致.结论 anti-GBM与anti-ds DNA和anti-NuA呈正相关;联合检测这些肾炎抗体对疾病的治疗和预后判断有指导意义.

  20. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases.

    Science.gov (United States)

    Lançon, Allan; Frazzi, Raffaele; Latruffe, Norbert

    2016-03-02

    Resveratrol (3,4',5 trihydroxy-trans-stilbene) is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD) is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  1. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

    Directory of Open Access Journals (Sweden)

    Allan Lançon

    2016-03-01

    Full Text Available Resveratrol (3,4′,5 trihydroxy-trans-stilbene is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  2. Anti-allergic, anti-inflammatory and anti-lipidperoxidant effects of Cassia occidentalis Linn.

    Science.gov (United States)

    Sreejith, G; Latha, P G; Shine, V J; Anuja, G I; Suja, S R; Sini, S; Shyama, S; Pradeep, S; Shikha, P; Rajasekharan, S

    2010-05-01

    Cassia occidentalis Linn. mast cell degranulation at a dose of 250 mg/kg, showed dose dependent stabilizing activity towards human RBC, with is widely used in traditional medicine of India to treat a number of clinical conditions including allergy and inflammatory manifestations. In the present study anti-allergic, anti-inflammatory and anti-oxidant properties of C. occidentalis whole plant ethanolic extract (CO) was investigated. Effects of CO on rat mast cell degranulation inhibition and human red blood cell (HRBC) membrane stabilization were studied in vitro following standard methods. The anti lipidperoxidant effects of CO were also studied in vitro. Effect of CO on carrageenan-induced mouse paw oedema inhibition was also assessed. CO significantly decreased maximum protection of 80.8% at 15 microg/ml. The extract also caused significant reduction in malondialdehyde (MDA) levels of murine hepatic microsomes at 100 microg/ml (56%) and significantly reduced carrageenan induced inflammation in mice at a dose of 250 mg/kg. Results of the present study indicated that CO inhibited mast cell degranulation, stabilized HRBC membrane thereby alleviating immediate hypersensitivity besides showing anti oxidant activity.

  3. In vivo Cytotoxicity of Type I CD20 Antibodies Critically Depends on Fc Receptor ITAM Signaling

    NARCIS (Netherlands)

    de Haij, Simone; Jansen, J. H. Marco; Boross, Peter; Beurskens, Frank J.; Bakema, Jantine E.; Bos, Desiree L.; Martens, Anton; Verbeek, J. Sjef; Parren, Paul W. H. I.; van de Winkel, Jan G. J.; Leusen, Jeanette H. W.

    2010-01-01

    Antibody-Fc receptor (FcR) interactions play an important role in the mechanism of action of most therapeutic antibodies against cancer. Effector cell activation through FcR triggering may induce tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC). Reciprocally, FcR cross-linking

  4. EU Lobbying and Anti-Dumping Policy

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Svendsen, Gert Tinggaard

    2012-01-01

    of petitioning firms and Council voting in the case of anti-dumping policy. If the political position of countries in anti-dumping cases is influenced by domestic lobbying efforts, we expect that the empirical pattern of country distribution of petitioning firms in EU anti-dumping cases corresponds closely...... to the empirical pattern of EU country distribution in Council voting. Our results show a low petitioning intensity for anti-dumping investigations and a high voting intensity against anti-dumping measures in Northern Europe. Thus, it seems likely that domestic lobbying efforts have influenced the political...... position of countries in the special case of EU anti-dumping policy....

  5. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    OpenAIRE

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheum...

  6. Impact of leptonic tau decays on the distribution of anti B → Dμ anti ν

    Energy Technology Data Exchange (ETDEWEB)

    Bordone, Marzia; Isidori, Gino; Dyk, Danny van [Physik-Institut, Universitaet Zuerich, Winterthurer Strasse 190, 8057 Zuerich (Switzerland)

    2016-07-01

    We present results for the decay rate of anti B → Dτ(→ μ anti νν) anti ν, which is a sizeable background to anti B → Dμ anti ν decays. In particular, we calculate analytically the differential decay rate with respect to all seven kinematic variables. We consider the impact of this decay on the distributions of anti B → Dμ anti ν in either the muon helicity angle or the muon energy in the anti B rest frame. Our numerical results are obtained from Monte Carlo pseudo events. Finally, we provide necessary information for cross checks of the experimental analyses.

  7. Pendidikan Anti Korupsi Berbasis Agama

    Directory of Open Access Journals (Sweden)

    Kasinyo Harto

    2016-03-01

    Full Text Available Tulisan ini memfokuskan pada pendidikan anti korupsi melalui perspektif agama dengan model rekonstruksi sosial. Pendekatan teoritis pendidikan  antikorupsi berbasis agama berupaya melihat sejauhmana realitas masyarakat religius dapat diakomodasi dalam aspek-aspek Pendidikan Anti-Korupsi, baik pada aspek materi, metode pembelajaran, evaluasi, dan sebagainya. Dengan pendekatan seperti itu, tulisan ini diharapkan mampu melakukan analisis-sintesis yang menghasilkan konsep-konsep teoritis PAK berbasis agama yang visibel untuk diterapkan dalam proses pembelajaran di kelas dan berhasil dalam implementasinya pada kehidupan sehari-hari. Jika konsep ini mungkin diterapkan, maka diharapkan akan terjadi perubahan dalam cara pandang peserta didik terhadap nilai agama yang dapat diterapkan dalam kehidupan empiris. Dampak lebih jauh dan jangka panjang diharapkan bahwa proses menuju masyarakat Indonesia yang bersih semakin  akan dapat diwujudkan. This paper focused on the anti-corruption education through religion perspective with social reconstruction model. The theoretical approach of anti-corruption education based religion sought to see how far the reality of religious communities could be accommodated in the aspects of Anti-Corruption Education, both in material aspects, teaching methods, evaluation, and so on. With that approach, this paper was expected to do the analysis-synthesis that produced theoretical concepts PAK-based religion that was visible to be applied in the learning process in the classroom and succeed in its implementation in daily life. If this concept might be applied, it was expected that there would be changes in learners' perspective on religion values that could be applied in empirical life. Further impacts and long-term it was expected that the process towards the Indonesian societies who clean more would be created.

  8. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin.

    Science.gov (United States)

    Choi, Jae Sue; Islam, Md Nurul; Ali, Md Yousof; Kim, Eon Ji; Kim, Young Myeong; Jung, Hyun Ah

    2014-02-01

    Apigenin has gained particular interests in recent years as a beneficial and health promoting agent because of its low intrinsic toxicity. Vitexin and isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been known to possess potent anti-diabetic, anti-Alzheimer's disease (anti-AD), and anti-inflammatory activities. The present study was designed to investigate the anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C-glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic and anti-AD potentials, apigenin showed powerful antiinflammatory activity by inhibiting NO production and iNOS and COX-2 expression while vitexin and isovitexin were inactive. Therefore, it could be speculated that C-glycosylation of apigenin at different positions might be closely linked to relative intensity of anti-diabetic, anti-AD, and anti-inflammatory potentials.

  9. U.S. Anti-Doping Agency

    Science.gov (United States)

    ... 7, 2016 View All News Releases Our Anti-Doping Programs What does USADA do? What elements make ... symposium topic. More Information Spirit of Sport – Anti-Doping News USADA’s Spirit of Sport news hub contains ...

  10. The dataset from administration of single or combined immunomodulation agents to modulate anti-FVIII antibody responses in FVIII plasmid or protein primed hemophilia A mice

    Directory of Open Access Journals (Sweden)

    Chao Lien Liu

    2016-06-01

    Full Text Available Hemophilia A mice with pre-existing inhibitory antibodies against factor VIII (FVIII were treated with single agents, AMD3100 and GCS-F, respectively. Inhibitor titers in treated mice and control HemA inhibitors mice were followed over time. Total B cells and plasma cells (PCs were characterized by flow cytometry. HemA inhibitor mice were then treated with a combination regimen of IL-2/IL-2mAb complexes plus rapamycin and AMD3100. Finally, HemA inhibitor mice were treated with a new combination therapy using include IL-2/IL-2mAb complexes + Anti-CD20+AMD3100+G-CSF. The timeline of combination therapy was illustrated. Inhibitor titers following treatment in FVIII plasmid or protein induced inhibitor mice were evaluated overtime. A representative figure and gating strategies to characterize the subsets of Treg cells and B cells are presented. Please see http://dx.doi.org/10.1016/j.cellimm.2016.01.005 [1] for interpretation and discussion of these data and results.

  11. Anti-fouling bioactive surfaces.

    Science.gov (United States)

    Yu, Qian; Zhang, Yanxia; Wang, Hongwei; Brash, John; Chen, Hong

    2011-04-01

    Bioactive surfaces refer to surfaces with immobilized bioactive molecules aimed specifically at promoting or supporting particular interactions. Such surfaces are of great importance for various biomedical and biomaterials applications. In the past few years, considerable effort has been made to create bioactive surfaces by forming specific biomolecule-modified surfaces on a non-biofouling "base" or "background". Hydrophilic and bioinert polymers have been widely used as anti-fouling layers that resist non-specific protein interactions. They can also serve as "spacers" to effectively move the immobilized biomolecule away from the surface, thus enhancing its bioactivity. In this review we summarize several successful approaches for the design and preparation of bioactive surfaces based on different types of anti-fouling/spacer materials. Some perspectives on future research in this area are also presented.

  12. CERN anti-fraud policy

    CERN Multimedia

    2013-01-01

    In 2011, a working group on improved fraud prevention and management was established. The group was composed of the Director of Administration and General Infrastructure, the Head of the Human Resources Department, and the Heads of the Legal Service and Internal Audit. It recommended the adoption of a global fraud prevention and management policy.   The global fraud prevention and management policy was implemented through the CERN Anti-Fraud Policy, which was endorsed by the Enlarged Directorate in May 2012 and approved by the Director-General for entry into force on 1 January 2013. The CERN Anti-Fraud Policy defines the Organization’s policy in matters of fraud.  CERN has a zero tolerance approach towards fraud, as it would compromise the accomplishment of its objectives and undermine its functioning, credibility and reputation. The policy also states CERN’s commitment to the prevention, identification and investigation of fraud. All CERN contributors have a key rol...

  13. O Cinema Anti-guerra

    Directory of Open Access Journals (Sweden)

    Tom Burns

    2001-12-01

    Full Text Available Resumo: o presente trabalho procura estabelecer algumas características do filme anti-guerra a partir da premissa de que as diferenças culturais e raciais dos inimigos de guerra são apagadas e a noção de uma humanidade em comum, emotivamente atraente mas teoricamente problemática, e transmitida ao espectador Argumenta-se, aqui, no entanto, que tal mensagem humanística não constitui uma proposta utópica para pôr fim à guerra, mas sim uma proposta que vem a contrapor a ideologia patriótica usada pelos governos para justificar a guerra.  Palavras-chave: filmes de guerra, filmes anti-guerra, patriotismo, humanismo

  14. Corruption and Anti-Corruption

    OpenAIRE

    Larmour, Peter; Wolanin, Nick

    2013-01-01

    There is new international attention being given to the old problem of corruption. It has been taken up by international organisations, and driven by economic analysis. It is impatient of cultural justifications, and suspicious of state action. It is concerned with corruption prevention as much as detection, investigation and prosecution. Corruption and Anti-Corruption deals with the international dimensions of corruption, including campaigns to recover the assets of former dictators, and...

  15. (Anti-Hermitian Generalized (Anti-Hamiltonian Solution to a System of Matrix Equations

    Directory of Open Access Journals (Sweden)

    Juan Yu

    2014-01-01

    Full Text Available We mainly solve three problems. Firstly, by the decomposition of the (anti-Hermitian generalized (anti-Hamiltonian matrices, the necessary and sufficient conditions for the existence of and the expression for the (anti-Hermitian generalized (anti-Hamiltonian solutions to the system of matrix equations AX=B,XC=D are derived, respectively. Secondly, the optimal approximation solution min⁡X∈K⁡∥X^-X∥ is obtained, where K is the (anti-Hermitian generalized (anti-Hamiltonian solution set of the above system and X^ is the given matrix. Thirdly, the least squares (anti-Hermitian generalized (anti-Hamiltonian solutions are considered. In addition, algorithms about computing the least squares (anti-Hermitian generalized (anti-Hamiltonian solution and the corresponding numerical examples are presented.

  16. Anti-Cyclic Citrullinated Peptide (Anti-CCP and Anti-Mutated Citrullinated Vimentin (Anti-MCV Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Laura Gonzalez-Lopez

    2014-01-01

    Full Text Available We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP and anti-mutated citrullinated vimentin antibodies (anti-MCV with the presence of extra-articular (ExRA manifestations in 225 patients with rheumatoid arthritis (RA. Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40 and P=0.91, resp.. Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF; (P=0.01, anti-CCP (P=0.048, and anti-MCV (P=0.02. Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di (r=0.154, P=0.03, erythrocyte sedimentation rate (ESR; (r=0.155, P=0.03, and RF (P=0.254, P<0.001, whereas anti-MCV titres only correlated with RF (r=0.169, P=0.02. On adjusted analysis, ExRA was associated with longer age (P=0.015, longer disease duration (P=0.007, higher DAS-28 score (P=0.002, and higher HAQ-DI score (P=0.007, but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

  17. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    Science.gov (United States)

    Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto Daniel; Ponce-Guarneros, Manuel; Flores-Chavez, Alejandra; Salazar-Paramo, Mario; Cardona-Muñoz, Ernesto German; Fajardo-Robledo, Nicte Selene; Zavaleta-Muñiz, Soraya Amali; Garcia-Cobian, Teresa; Gamez-Nava, Jorge Ivan

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation. PMID:24804270

  18. Anti-backlash gear bearings

    Science.gov (United States)

    Vranish, John M. (Inventor)

    2009-01-01

    A gear bearing having a first gear and a second gear, each having a plurality of teeth. Each gear operates on two non-parallel surfaces of the opposing gear teeth to perform both gear and bearing functions simultaneously. The gears are moving at substantially the same speed at their contact points. The gears may be roller gear bearings or phase-shifted gear bearings, and may be arranged in a planet/sun system or used as a transmission. One preferred embodiment discloses and describes an anti-backlash feature to counter ''dead zones'' in the gear bearing movement.

  19. Environmentally friendly anti-icing

    Science.gov (United States)

    Lockyer, Robert T. (Inventor); Zuk, John (Inventor); Haslim, Leonard A. (Inventor)

    1998-01-01

    The present invention describes an aqueous, non-electrolytic, non-toxic, biodegradable, continuous single phase liquid anti-icing or deicing composition for use on the surfaces of, for example, aircraft, airport pavements, roadways, walkways, bridges, entrances, structures, canals, locks, components, vessels, nautical components, railroad switches, and motor vehicles. The anti-icing or deicing composition comprises: (a) water; (b) a non-toxic freezing point depressant selected from the group consisting of monohydric alcohols having from 2 to 6 carbon atoms, polyhydric alcohols having from 3 to 12 carbon atoms, monomethyl or ethyl ethers of polyhydric alcohols having from 3 to 12 atoms or mixtures thereof, wherein the freezing point depressant present is between about 14 to 60 percent by weight; (c) a thickener which is present in between about 0.01 and 10 percent by weight; and (d) optionally a corrosion inhibitor which is present in between about 0.01 and 0.1 percent by weight of the total composition. In one embodiment, the deicing composition further includes (e) a monohydric primary aliphatic unbranched alcohol as a means of forming a thin layer of the composition on the surface of the structure to be given ice protection, and/or as means of forming a homogenized foam with xanthan thickener; which alcohol is selected from the group consisting of alcohols having between 8 to 24 carbon atoms, preferably, 1-dodecanol. Compositions of water, propylene glycol, and/or propanol and xanthan are preferred.

  20. (Anti-)Hermitian Generalized (Anti-)Hamiltonian Solution to a System of Matrix Equations

    OpenAIRE

    Juan Yu; Qing-Wen Wang; Chang-Zhou Dong

    2014-01-01

    We mainly solve three problems. Firstly, by the decomposition of the (anti-)Hermitian generalized (anti-)Hamiltonian matrices, the necessary and sufficient conditions for the existence of and the expression for the (anti-)Hermitian generalized (anti-)Hamiltonian solutions to the system of matrix equations AX=B,XC=D are derived, respectively. Secondly, the optimal approximation solution min⁡X∈K⁡∥X^-X∥ is obtained, where K is the (anti-)Hermitian generalized (anti-)Hamiltonian solution set of t...

  1. Anti S enigma in a pregnant patient.

    Science.gov (United States)

    Kaur, Paramjit; Kaur, Gagandeep; Basu, Sabita; Kaur, Ravneet

    2014-04-01

    Among the antibodies of the MNS blood group system, anti S antibody is generally IgG antibody reacting at 37 °C. It is rarely implicated in hemolytic transfusion reaction; however, it can lead to potentially severe transfusion reactions. Anti S is also capable of causing mild to severe fatal hemolytic disease of newborn. We report a case of anti S antibody in a pregnant patient with complicated falciparum malaria.

  2. Exploring heterosexual women's anti-lesbian attitudes.

    Science.gov (United States)

    Wilkinson, Wayne W

    2006-01-01

    Previous research on attitudes toward gays has mostly focused on heterosexuals' attitudes toward gay men, with little research specifically directed at anti-lesbian attitudes. Using a sample of 269 undergraduate heterosexual women, the present study tested two feminist propositions: Anti-lesbian attitudes would be associated with (1) conservative beliefs regarding the female gender-role and (2) attitudes toward men that support the differential status of women and men in the patriarchy. Findings based on a series of multiple regression analyses support these propositions across three components of anti-lesbian attitudes (contact apprehension, morality beliefs, and stereotypic beliefs). Directions for future research on anti-lesbian attitudes are discussed.

  3. The Superheavy Elements and Anti-Gravity

    Science.gov (United States)

    Anastasovski, Petar K.

    2004-02-01

    The essence of any propulsion concept is to overcome gravity. Anti-gravity is a natural means to achieve this. Thus, the technology to pursue anti-gravity, by using superheavy elements, may provide a new propulsion paradigm. The theory of superluminal relativity provides a hypothesis for existence of elements with atomic number up to Z = 145, some of which may possess anti-gravity properties. Analysis results show that curved space-time exists demonstrating both gravitic and anti-gravitic properties not only around nuclei but inside the nuclei as well. Two groups of elements (Z Hawking, in honour of Stephen W. Hawking.

  4. SISTEM PENDIDIKAN KEAGAMAAN ANTI KORUPSI

    Directory of Open Access Journals (Sweden)

    Atiqullah Atiqullah

    2012-03-01

    Full Text Available AbstractThis article presents three important aspects  of an Islamic education system, namely the purpose of education, curriculum, and strong leadership system. Empowerment of the  sub system of religious education is always be prophetic moral messages for the life of the community's anti-corruption in the form of instilled-honesty values, exemplary of the leaders of institutions’  values, as well as oriented curriculum, namely Manhaj al-Tarbiyah al-Islamiyah, Wasilat al-Tarbiyah al-Islamiyah, Kayfiyat al-Tarbiyah al-Islamiyah, and Thariqat al-Tarbiyah al-Islamiyah are  methodology and strategy in the process of achieving Islamic education, namely self actualized.Kata-kata kunciperilaku korupsi, sistem pendidikan, tujuan, kurikulum, dan kepemimpinan

  5. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  6. Science and anti-science

    CERN Document Server

    Holton, Gerald

    1997-01-01

    What is good science? What goal--if any--is the proper end of scientific activity? Is there a legitimating authority that scientists mayclaim? Howserious athreat are the anti-science movements? These questions have long been debated but, as Gerald Holton points out, every era must offer its own responses. This book examines these questions not in the abstract but shows their historic roots and the answers emerging from the scientific and political controversies of this century. Employing the case-study method and the concept of scientific thematathat he has pioneered, Holton displays the broad scope of his insight into the workings of science: from the influence of Ernst Mach on twentiethcentury physicists, biologists, psychologists, and other thinkers to the rhetorical strategies used in the work of Albert Einstein, Niels Bohr, and others; from the bickering between Thomas Jefferson and the U.S. Congress over the proper form of federal sponsorship of scientific research to philosophical debates since Oswald...

  7. Configuring Symantec AntiVirus

    CERN Document Server

    Shimonski, Robert

    2003-01-01

    This is the only book that will teach system administrators how to configure, deploy, and troubleshoot Symantec Enterprise Edition in an enterprise network. The book will reflect Symantec''s philosophy of "Centralized Antivirus Management." For the same reasons that Symantec bundled together these previously separate products, the book will provide system administrators with a holistic approach to defending their networks from malicious viruses. This book will also serve as a Study Guide for those pursuing Symantec Product Specialist Certifications.Configuring Symantec AntiVirus Enterprise Edition contains step-by-step instructions on how to Design, implement and leverage the Symantec Suite of products in the enterprise.ØFirst book published on market leading product and fast-growing certification. Despite the popularity of Symantec''s products and Symantec Product Specialist certifications, there are no other books published or announced.ØLess expensive substitute for costly on-sight training. Symantec off...

  8. Natural anti-obesity agents

    Directory of Open Access Journals (Sweden)

    Gamal A. Mohamed

    2014-12-01

    Full Text Available Obesity is a complex disease caused by the interaction of a myriad of genetic, dietary, lifestyle, and environmental factors, which favors a chronic positive energy balance, and leads to increased body fat mass. The incidence of obesity is rising at an alarming rate and is becoming a major public health concern with incalculable social costs. Indeed, obesity facilitates the development of metabolic disorders such as diabetes, hypertension, and cardiovascular diseases in addition to chronic diseases such as stroke, osteoarthritis, sleep apnea, some cancers, and inflammation-based pathologies. Recent researches demonstrated the potential of natural products to counteract obesity. Multiple-natural product combinations may result in a synergistic activity that increases their bioavailability and action on multiple molecular targets, offering advantages over chemical treatments. In this review, we discuss the anti-obesity potential of natural products and analyze their mechanisms.

  9. In vitro anti-glycation and anti-oxidant properties of synthesized Schiff bases.

    Science.gov (United States)

    Jhaumeer-Laulloo, Sabina; Bhowon, Minu Gupta; Mungur, Shabneez; Mahomoodally, Mohamad Fawzi; Subratty, Anwar Hussein

    2012-05-01

    A series of mono, bis and mixed Schiff bases (1-7) were synthesised and evaluated for potential anti-glycation and anti-oxidant activities using the bovine serum albumin-glucose assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay respectively. All compounds showed significant (papplications that warrant further investigation as potential anti-glycation and anti-oxidant agents which could be of importance in metabolic diseases including diabetes mellitus.

  10. Anti-cyclic citrullinated peptide (anti-CCP) antibodies with brucellosis.

    Science.gov (United States)

    Kisacik, Bunyamin; Dag, Muhammet Said; Pehlivan, Yavuz; Ugurlu, Kenan; Mercan, Ozge Kaya; Aydinli, Musa; Devay, Seda Duygulu; Sayarlioglu, Mehmet; Onat, Ahmet Mesut

    2014-06-01

    Anti-cyclic citrullinated peptide (anti-CCP) was positive in 11.5 % and rheumatoid factor was positive in 8.8 % of the patients with Brucella. After a comparative evaluation, we have found out that there was not a statistical significance concerning the anti-CCP levels between the patients with brucellosis and healthy control.

  11. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  12. Anti-calculus and whitening toothpastes.

    Science.gov (United States)

    van Loveren, Cor; Duckworth, Ralph M

    2013-01-01

    In terms of novel formulations, there seems to have been a shift in emphasis from anti-caries/anti-gingivitis to anti-calculus/whitening toothpastes in recent years. The anti-calculus and whitening effects of toothpastes are to some extent based on the same active ingredients: compounds of high affinity for tooth mineral. Due to this affinity, crystal growth may be hindered (anti-calculus) and chromophores be displaced (whitening). Besides these common ingredients, both types of toothpaste may contain agents specifically aimed at each condition. Clinical studies have shown that these active ingredients can be successfully formulated in fluoride toothpastes to give significant reductions in supragingival calculus and stain formation and facilitate their removal. Some of the ingredients are formulated in toothpastes that additionally contain anti-plaque and anti-gingivitis ingredients, making these toothpastes (together with the fluoride) truly multi-functional. The development of these products is not straightforward because of interaction between formulation components and because the active ingredients must maintain their beneficial characteristics during the shelf life of the paste. Neither a therapeutic benefit (in terms of less gingivitis or less caries) nor a societal benefit (in terms of less treatment demand) has been demonstrated as a result of the anti-calculus and whitening effects of toothpastes.

  13. Anti-Dumping on and from China

    Institute of Scientific and Technical Information of China (English)

    Patrick H. Zhao

    2007-01-01

    @@ The past years saw an increased cases of anti-dumping on China mostly from the developed countries, some from developing countries. But Pakistan, a friendly neighbor to China, recently adds up to that list of ranks for an anti-dumping investigation on China.

  14. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M.

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  15. Discrimination and Anti-discrimination in Denmark

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

    The purpose of this report is to describe and analyse Danish anti-discrimination legislation and the debate about discrimination in Denmark in order to identify present and future legal challenges. The main focus is the implementation of the EU anti-discrimination directives in Danish law...

  16. Poliarterite nodosa due to anti elastase antibody

    Directory of Open Access Journals (Sweden)

    Caterina Defendenti

    2008-09-01

    Full Text Available The Authors related one case of polyarteritis nodosa occurred to a men forty eight years old.The clinical was characterized by mesenteric and femoral arteries occlusion and chronic cutaneous ulcers to legs. There were bioptical aspects of systemic vasculitis with necrotizing inflammation and a paucity of immune deposit. It was effective oral cyclophosphamide plus steroids. This disease was closely associated with antibodies anti elastase (HLE.The patient had not a history of cocaine abuse or LES disease but the nucleolar pattern ANA was positive >1:640 (anti-nDNA negative. Similar case ANA positive associated with the anti-elastase antibodies, was described by Nassberger (Lancet 1989 for 6/104 patients with LES, anti-nDNA negative. The patient with the highest anti-elastase concentration subsequentely died after very rapid development of severe brain and kidney involvement.

  17. Transformations in French Anti-Semitism

    Directory of Open Access Journals (Sweden)

    Nonna Mayer

    2007-01-01

    Full Text Available The increase in the number of anti-Semitic acts since the start of the Second Intifada has sparked off a broad debate on the return of anti-Semitism in France. This article focuses on the question whether this anti-Semitism is still based on the alleged superiority of the Aryan race as in the time of Nazism, or if it represents the birth of a “new Judeophobia” that is more based on anti-Zionism and the polemical mixing of “Jews,” “Israelis,” and “Zionists.” One supposed effect of this transformation is that anti-Semitism is in the process of changing camps and migrating from the extreme right to the extreme left of the political arena, to the “altermondialistes,” the communists, and the “neo-Trotskyists.”

  18. Salinomycin: a novel anti-cancer agent with known anti-coccidial activities.

    Science.gov (United States)

    Zhou, Shuang; Wang, Fengfei; Wong, Eric T; Fonkem, Ekokobe; Hsieh, Tze-Chen; Wu, Joseph M; Wu, Erxi

    2013-01-01

    Salinomycin, traditionally used as an anti-coccidial drug, has recently been shown to possess anti-cancer and anti-cancer stem cell (CSC) effects, as well as activities to overcome multi-drug resistance based on studies using human cancer cell lines, xenograft mice, and in case reports involving cancer patients in pilot clinical trials. Therefore, salinomycin may be considered as a promising novel anti-cancer agent despite its largely unknown mechanism of action. This review summarizes the pharmacologic effects of salinomycin and presents possible mechanisms by which salinomycin exerts its anti-tumorigenic activities. Recent advances and potential complications that might limit the utilization of salinomycin as an anti-cancer and anti-CSC agent are also presented and discussed.

  19. [Anti-NMDA-receptor encephalitis].

    Science.gov (United States)

    Engen, Kristine; Agartz, Ingrid

    2016-06-01

    BACKGROUND In 2007 a clinical disease caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor was described for the first time. Anti-NMDA-receptor encephalitis is a subacute, autoimmune neurological disorder with psychiatric manifestations. The disease is a form of limbic encephalitis and is often paraneoplastic. The condition is also treatable. In this review article we examine the development of the disease, clinical practice, diagnostics and treatment.MATERIAL AND METHOD The article is based on references retrieved from searches in PubMed, and a discretionary selection of articles from the authors' own literature archive.RESULTS The disease most frequently affects young women. It may initially be perceived as a psychiatric condition, as it usually presents in the form of delusions, hallucinations or mania. The diagnosis should be suspected in patients who later develop neurological symptoms such as various movement disorders, epileptic seizures and autonomic instability. Examination of serum or cerebrospinal fluid for NMDA receptor antibodies should be included in the assessment of patients with suspected encephalitis. MRI, EEG and assessment for tumours are important tools in diagnosing the condition and any underlying malignancy.INTERPRETATION If treatment is initiated early, the prognosis is good. Altogether 75 % of patients will fully recover or experience significant improvement. Apart from surgical resection of a possible tumour, the treatment consists of immunotherapy. Because of good possibilities for treatment, it is important that clinicians, particularly those in acute psychiatry, are aware of and alert to this condition.

  20. Anti-TNFa treatment in patients with rheumatoid arthritis and anti-Ro/SSA antibodies

    Directory of Open Access Journals (Sweden)

    P. Airò

    2011-09-01

    Full Text Available Objective: To analyse clinical efficacy, onset of new autoantibodies or symptoms of autoimmune disease in patients affected by rheumatoid arthritis with anti-Ro/SSA treated with anti-TNFa agents. Methods: Six anti-Ro/SSA positive subjects with RA were studied every six months until 24th month of treatment in order to detect ANA titer (IFI, anti-dsDNA (Farr, anti-cardiolipin and anti-beta2glycoprotein I (ELISA, anti-ENA (CIE. The titre of anti-Ro/SSA were analysed by ELISA. Four patients were diagnosed as overlap RA/SS. Results: Six female patients (mean age 58ys, SD 9.8ys, with long-standing RA (mean 7ys, range 5-22 ys were treated with anti-TNFa agents for a mean of 31 months (SD: 20.4 m: 4 with Infliximab and 2 with Etanercept. All the patients showed a significant reduction of DAS until 24th month (p<0.006 with stability of sicca symptoms. The titer of ANA and anti-Ro/SSA was stable, while 4 subjects developed anti-dsDNA at low titer within 6-12 months. One patient withdrawn the treatment, because of lupus-like features; another one, with HCV hepatitis, interrupted Etanercept because of elevation of liver enzymes. No anticardiolipin or antibeta2GPI antibodies were detected. One subject with RA-SS also presented a primary biliary cirrhosis: clinical and histological features of cholangitis remained stable during Etanercept treatment. Conclusions: Anti-TNFa treatment showed good efficacy and safety in anti-Ro/SSA positive patients with RA. Anti-ds- DNA antibodies at low titer appeared in most patients while the onset of lupus-like disease could be considered a rare event also in RA patients with a rich autoimmune repertoire.

  1. Anti-malarial, anti-algal, anti-tubercular, anti-bacterial, anti-photosynthetic, and anti-fouling activity of diterpene and diterpene isonitriles from the tropical marine sponge Cymbastela hooperi.

    Science.gov (United States)

    Wright, Anthony D; McCluskey, Adam; Robertson, Mark J; MacGregor, Kylie A; Gordon, Christopher P; Guenther, Jana

    2011-01-21

    In an investigation into their potential ecological role(s), a group of mainly diterpene isonitriles, nine in total, isolated from the tropical marine sponge Cymbastela hooperi, and the sesquiterpene axisonitrile-3, isolated from the tropical marine sponge Acanthella kletra, were evaluated in a series of bioassays including anti-fouling, anti-algal, anti-photosynthetic, anti-bacterial (Gram +ve and -ve), anti-fungal, and anti-tubercular. The results of these assays showed that all of the tested compounds, with the exception of diterpene 9, were active in at least two of the applied test systems, with axisonitrile-3 (10) and diterpene isonitrile 1 being the two most active compounds overall, closely followed by diterpene isonitrile 3. Based on the results of the photosynthetic study a molecular modelling investigation was undertaken with all of the compounds used in that study. The results showed a positive correlation between reduction in photosynthetic activity and the interaction of the modelled compounds with a potential enzyme active site.

  2. Electromagnetic anti-jam telemetry tool

    Science.gov (United States)

    Ganesan, Harini; Mayzenberg, Nataliya

    2008-02-12

    A mud-pulse telemetry tool includes a tool housing, a motor disposed in the tool housing, and a magnetic coupling coupled to the motor and having an inner shaft and an outer shaft. The tool may also include a stator coupled to the tool housing, a restrictor disposed proximate the stator and coupled to the magnetic coupling, so that the restrictor and the stator adapted to generate selected pulses in a drilling fluid when the restrictor is selectively rotated. The tool may also include a first anti-jam magnet coupled to the too housing, and an second anti-jam magnet disposed proximate the first anti-jam magnet and coupled to the inner shaft and/or the outer shaft, wherein at least one of the first anti-jam magnet and the second anti-jam magnet is an electromagnet, and wherein the first anti-jam magnet and the second anti-jam magnet are positioned with adjacent like poles.

  3. Novel agents for anti-platelet therapy

    Directory of Open Access Journals (Sweden)

    Ji Xuebin

    2011-11-01

    Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

  4. The anti-proton charge radius

    CERN Document Server

    Crivelli, P; Heiss, M W

    2016-01-01

    The upcoming operation of the Extra Low ENergy Antiprotons (ELENA) ring at CERN, the upgrade of the anti-proton decelerator (AD), and the installation in the AD hall of an intense slow positron beam with an expected flux of $10^{8}$ e$^+$/s will open the possibility for new experiments with anti-hydrogen ($\\bar{\\text{H}}$). Here we propose a scheme to measure the Lamb shift of $\\bar{\\text{H}}$. For a month of data taking, we anticipate an uncertainty of 100 ppm. This will provide a test of CPT and the first determination of the anti-proton charge radius at the level of 10%.

  5. Isoimmunization with anti-U antibody.

    Science.gov (United States)

    Turner, R J; Holder, W T; McCord, D L

    1984-03-01

    Isoimmunization with anti-U antibody is a rare but significant cause of hemolytic disease in black newborns. In this case report, an lgG antibody stimulated by fetomaternal transfusion produced a positive direct Coombs' test on cord blood but not neonatal hyperbilirubinemia. A review of the literature suggests the pathophysiology is similar to Rh isoimmunization. The anti-U antibody may develop as a result of pregnancy or blood transfusion in the 1.2 percent of American blacks who are at risk for developing the antibody. The principles of treatment employed in Rh isoimmunization can be successfully used in isoimmunization due to anti-U.

  6. Anti-Dumping on and from China

    Institute of Scientific and Technical Information of China (English)

    Patrick; H.Zhao

    2007-01-01

    The past years saw an increased cases of anti-dumping on China mostly from the developed countries,some from developing countries.But Pakistan,a friendly neighbor to China,recently adds up to that list of ranks for an anti-dumping investigation on China.It is the national interests that count most,after all. It gives out a signal that anti-dumping would be a frequent tool to defend or to attack. Evidences show China is a target for this trade remedy,but is also targeting others.

  7. Anti-Atlas Mountains, Morocco

    Science.gov (United States)

    2003-01-01

    The Anti-Atlas Mountains of Morocco formed as a result of the collision of the African and Eurasian tectonic plates about 80 million years ago. This collision destroyed the Tethys Ocean; the limestone, sandstone, claystone, and gypsum layers that formed the ocean bed were folded and crumpled to create the Atlas and Anti-Atlas Mountains. In this ASTER image, short wavelength infrared bands are combined to dramatically highlight the different rock types, and illustrate the complex folding. The yellowish, orange and green areas are limestones, sandstones and gypsum; the dark blue and green areas are underlying granitic rocks. The ability to map geology using ASTER data is enhanced by the multiple short wavelength infrared bands, that are sensitive to differences in rock mineralogy. This image was acquired on June 13, 2001 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet.ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products.The broad spectral coverage and high spectral resolution of ASTER will provide scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and

  8. The Effects of Houttuyniae Herba extract on the Activity of Anti-bacteria, Anti-inflammation and Anti-oxidation

    OpenAIRE

    Oh-do Jeon; Hyeong-sik Seo

    2008-01-01

    Objective : This experimental study was performed to investigate the effects of Houttuyniae Herba extract on anti-inflammation and anti-oxidation. Methods : The cytotoxicity of Houttuyniae Herba water extract and ethanol extract about viability of Raw 264.7 cell were tested using a colormetric tetrazolium assay(MTT assay). We investigated the inhibitory effects of Houttuyniae Herba water extract and ethanol extract on Propionibactrium acnes using paper disk diffusion method. To in...

  9. From anti-conformism to extremism

    CERN Document Server

    Weisbuch, Gérard

    2015-01-01

    We here present a model of the dynamics of extremism based on opinion dynamics in order to understand the circumstances which favour its emergence and development in large fractions of the general public. Our model is based on the bounded confidence hypothesis and on the evolution of initially anti-conformist agents to extreme positions. Numerical analyses demonstrate that a few anti-conformists are able to drag a large fraction of conformists agents to their position provided that they express their views more often than the conformists. The most influential parameter controlling the outcome of the dynamics is the uncertainty of the conformist agents; the higher their uncertainty, the higher is the influence of anti-conformists. Systematic scans of the parameter space show the existence of two regime transitions, one following the conformists uncertainty parameter and the other one following the anti-conformism strength.

  10. Marine Organisms with Anti-Diabetes Properties

    Directory of Open Access Journals (Sweden)

    Chiara Lauritano

    2016-12-01

    Full Text Available Diabetes is a chronic degenerative metabolic disease with high morbidity and mortality rates caused by its complications. In recent years, there has been a growing interest in looking for new bioactive compounds to treat this disease, including metabolites of marine origin. Several aquatic organisms have been screened to evaluate their possible anti-diabetes activities, such as bacteria, microalgae, macroalgae, seagrasses, sponges, corals, sea anemones, fish, salmon skin, a shark fusion protein as well as fish and shellfish wastes. Both in vitro and in vivo screenings have been used to test anti-hyperglycemic and anti-diabetic activities of marine organisms. This review summarizes recent discoveries in anti-diabetes properties of several marine organisms as well as marine wastes, existing patents and possible future research directions in this field.

  11. Entanglement in joint Λ anti Λ decay

    Energy Technology Data Exchange (ETDEWEB)

    Faeldt, Goeran [Uppsala University, Department of Physics and Astronomy, Uppsala (Sweden)

    2015-07-15

    We investigate the joint Λ anti Λ decay in the reaction e{sup +}e{sup -} → γΛ(→ pπ{sup -}) anti Λ(→ anti pπ{sup +}). This reaction may provide information on the electromagnetic form factors of the Lambda baryon, in the time-like region. We present a conventional diagram-based calculation where production and decay steps are coherent and summations over final-state proton and anti-proton spins are performed. The resulting cross-section distribution is explicitly covariant as it is expressed in scalar products of the four-momentum vectors of the participating particles. We compare this calculation with that of the folding method which we extend and make explicitly covariant. In the folding method production and decay distributions, not amplitudes, are folded together. Of particular importance is then a correct counting of the number of possible intermediate-hyperon-spin states. (orig.)

  12. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    based on immunopharmacological evidence from individual patients (personalized medicine) is the use of assays for anti-drug antibodies (ADA) that are accurate and relevant in the clinical setting. This paper discusses immunogenicity of genetically engineered immunoglobulins directed against tumor...

  13. Laparoscopic Anti-Reflux (GERD) Surgery

    Science.gov (United States)

    ... Sponsorship Opportunities Log In Laparoscopic Anti-Reflux (GERD) Surgery Patient Information from SAGES Download PDF Find a SAGES Surgeon Surgery for “Heartburn” If you suffer from moderate to ...

  14. Disciplinarian Heads Anti-Corruption Bureau

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China has recently ramped up its anti-corruption efforts by establishing the National Corruption Prevention Bureau(NCPB).Appointed to lead the bureau,which falls under the Chinese Central Government,is

  15. Anti-CD40-mediated cancer immunotherapy

    DEFF Research Database (Denmark)

    Hassan, Sufia Butt; Sørensen, Jesper Freddie; Olsen, Barbara Nicola

    2014-01-01

    activation and thus enhancement of immune responses. Treatment with anti-CD40 monoclonal antibodies has been exploited in several cancer immunotherapy studies in mice and led to the development of anti-CD40 antibodies for clinical use. Here, Dacetuzumab and Lucatumumab are in the most advanced stage...... with other cancer immunotherapies, in particular interleukin (IL)-2. An in-depth analysis of this immunotherapy is provided elsewhere. In the present review, we provide an update of the most recent clinical trials with anti-CD40 antibodies. We present and discuss recent and ongoing clinical trials...... in this field, including clinical studies which combine anti-CD40 treatment with other cancer-treatments, such as Rituximab and Tremelimumab....

  16. Anti-Secession Law Reflects Common Will

    Institute of Scientific and Technical Information of China (English)

    王宏远

    2005-01-01

    @@ Chinese top legislator Wu Bangguo on Dec.29, 2004 promised that the 10th National People's Congress (NPC) would do its best to fully reflect the common will of all Chinese people in making the anti-secession law.

  17. Anti-ulcer potential of Oxystelma esculentum

    Directory of Open Access Journals (Sweden)

    Devang J Pandya

    2011-01-01

    Full Text Available Oxystelma esculentum is a perennial twiner growing near water-logged areas in the Indian subcontinent. It is used traditionally in stomach ulcers. The present work deals with the investigation of anti-ulcer potential of O. esculentum. The plant was successively extracted with solvents of varying polarities, which served as the test extracts. Anti-ulcer effect was checked in Wistar rats using aspirin- and ethanol-induced acute ulcer models. The petroleum ether extract was found to possess the most effective anti-ulcer activity. This proves the traditional claim of the plant as an anti-ulcer drug. Phytochemical screening of this extract revealed the presence of important classes of compounds like cardenolides, flavonoids, phenolics, sterols and triterpenoids. This bioactivity-guided phytochemical screening can guide further therapeutic investigations and isolation of pharmacologically active compounds from Oxystelma esculentum.

  18. ASACUSA Anti-protonic Helium_Final

    CERN Document Server

    CERN Audiovisual Production Service; CERN AD; Paola Catapano; Julien Ordan, Arzur Catel; Paola Catapano; ASACUSA COLLABORATION

    2016-01-01

    Latest precision measurement of the mass of the proton and the anti proton though the production of antiprotonic helium by the ASACUSA experiment at CERN's antimatter factory, with a beam from the Antiproton Decelerator

  19. Measurement of b anti b correlations at the CERN p anti p collider

    Energy Technology Data Exchange (ETDEWEB)

    Albajar, C.; Ankoviak, K.; Bartha, S.; Bezaguet, A.; Boehrer, A.; Bos, K.; Buchanan, C.; Buschbeck, B.; Castilla-Valdez, H.; Cennini, P.; Cittolin, S.; Clayton, E.; Cline, D.; Caughlan, J.A.; Dau, D.; Daum, C.; Della Negra, M.; Demoulin, M.; Denegri, D.; Dibon, H.; Dorenbosch, J.; Dowell, J.D.; Eggert, K.; Eisenhandler, E.; Ellis, N.; Evans, H.; Faissner, H.; Fensome, I.F.; Fortson, L.; Garvey, J.; Geiser, A. Givernaud, A.; Gonidec, A.; Gonzalez, B.; Gronberg, J.; Holthuizen, D.J.; Jank, W.; Jorat, G.; Kalmus, P.I.P.; Karimaeki, V.; Kenyon, I.; Kinnunen, R.; Krammer, M.; Lammel, S.; Landon, M.P.J.; Lemoigne, Y.; Levegruen, S.; Lipa, P.; Markou, C.; Markytan, M.; Maurin, G.; McMahon, S.; Merlo, J.P.; Meyer, T.; Moers, T.; Mohammadi, M.; Morsch, A.; Moulin, A.; Norton, A.; Otwinowski, S.; Pancheri, G.; Pietarinen, E.; Pimiae, M.; Placci, A.; Porte, J.P.; Priem, R.; Prosi, R.; Radermacher, E.; Rauschkolb, M.; Reithler, H.; Revol, J.P.; Robinson, D.; Rubbia, C.; Samyn, D.; Schinzel, D.; Sc; UA1 Collaboration

    1994-01-01

    We report on measurements of correlated b anti b production in p anti p at [radical]s=630 GeV, using dimuon data to tag both the b and anti b quarks. Starting from an inclusive dimuon sample we obtain improved cross-sections for single inclusive beauty production and confirm our earlier results on B[sup 0]- anti B[sup 0] mixing. From a study of b anti b correlations we derive explicit cross-sections for semi-differential b anti b production. We compare the measured cross-sections and correlations to OMIKRON ([alpha][sub s][sup 3]) QCD predictions and find good quantitative agreement. From the measured angular distributions we establish a sizeable contribution from higher order QCD processes with a significance of about seven standard deviations. A large nonperturbative contribution to these higher order corrections is excluded. (orig.)

  20. Confidence in Anti-Trust Laws

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Cooperation between Chinese and U.S. anti-monopoly enforcers is helping China improve its laws to encourage free competition china and the United States signed a memorandum of understanding regarding cooperation in antitrust and anti-monopoly investigations in Beijing on July 27. China’s National Development and Reform Commission (NDRC), Ministry of Commerce (MOFCOM) and State Administration for Industry and Commerce (SAIC) signed the document with the U.S. Department of Justice and Federal Trade Commission (FTC).

  1. ANTI-INFLAMMATORY ACTIVITY OF DODONAEA VISCOSE

    OpenAIRE

    Mahadevan, N.; Venkatesh, Sama; Suresh, B

    1998-01-01

    Dodonaea viscose, Linn is a widely grown plant of Nilgiris district of Tamil and is commonly used by the tribals of Nilgiris as a traditional medicine for done fracture and joint sprains. Since it is generally believed tat fractures are accompanied by either some degree of injury or inflammations, it was felt desirable to carry our anti inflammatory activity of Dodonaea viscose. Anti-inflammatory activity of the plant was carried out by carrageenin induced paw edema method in Wister albino rats.

  2. Anti-inflammatory activity of dodonaea viscose.

    Science.gov (United States)

    Mahadevan, N; Venkatesh, S; Suresh, B

    1998-10-01

    Dodonaea viscose, Linn is a widely grown plant of Nilgiris district of Tamil and is commonly used by the tribals of Nilgiris as a traditional medicine for done fracture and joint sprains. Since it is generally believed tat fractures are accompanied by either some degree of injury or inflammations, it was felt desirable to carry our anti inflammatory activity of Dodonaea viscose. Anti-inflammatory activity of the plant was carried out by carrageenin induced paw edema method in Wister albino rats.

  3. Canadian National Identity and Anti-Americanism

    Institute of Scientific and Technical Information of China (English)

    谭万宏

    2015-01-01

    Canadian national identity is closely related to antiAmericanism and for Canadians,comparing with America has become the main way to identify themselves.So some scholars argue that Canada lacks a real national identity and this is the main reason of its anti-American tradition.However,the author remarks Canada has its national identity.In this paper,the author will present three reasons to support her view.

  4. Canadian National Identity and Anti-Americanism

    Institute of Scientific and Technical Information of China (English)

    谭万宏

    2015-01-01

    Canadian national identity is closely related to anti-Americanism and for Canadians,comparing with America has become the main way to identify themselves.So some scholars argue that Canada lacks a real national identity and this is the main reason of its anti-American tradition.However,the author remarks Canada has its national identity.In this paper,the author will present three reasons to support her view.

  5. Nonsteroid Anti-inflammatory Drugs and Kidney

    OpenAIRE

    Yaşar Yıldırım; Zülfükar Yılmaz; A. Veysel Kara1; et al.,

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydr...

  6. Cultural diversity and anti-poverty policy.

    Science.gov (United States)

    Lamont, Michèle; Small, Mario Luis

    2010-01-01

    This article examines how anti-poverty policy has considered the role of culture and how it ought to do so. While some have explained poverty as a function of the presumed cultural deficiency or distinctiveness of the poor, we suggest that these explanations have not been convincing and that policy requires a broader and more sophisticated understanding of the relationship between culture and behaviour. In fact, we suggest that cultural differences may be positively employed in comprehensive anti-poverty strategies.

  7. Characterization of multilayer anti-fog coatings.

    Science.gov (United States)

    Chevallier, Pascale; Turgeon, Stéphane; Sarra-Bournet, Christian; Turcotte, Raphaël; Laroche, Gaétan

    2011-03-01

    Fog formation on transparent substrates constitutes a major challenge in several optical applications requiring excellent light transmission characteristics. Anti-fog coatings are hydrophilic, enabling water to spread uniformly on the surface rather than form dispersed droplets. Despite the development of several anti-fog coating strategies, the long-term stability, adherence to the underlying substrate, and resistance to cleaning procedures are not yet optimal. We report on a polymer-based anti-fog coating covalently grafted onto glass surfaces by means of a multistep process. Glass substrates were first activated by plasma functionalization to provide amino groups on the surface, resulting in the subsequent covalent bonding of the polymeric layers. The anti-fog coating was then created by the successive spin coating of (poly(ethylene-maleic anhydride) (PEMA) and poly(vinyl alcohol) (PVA) layers. PEMA acted as an interface by covalently reacting with both the glass surface amino functionalities and the PVA hydroxyl groups, while PVA added the necessary surface hydrophilicity to provide anti-fog properties. Each step of the procedure was monitored by XPS, which confirmed the successful grafting of the coating. Coating thickness was evaluated by profilometry, nanoindentation, and UV visible light transmission. The hydrophilic nature of the anti-fog coating was assessed by water contact angle (CA), and its anti-fog efficiency was determined visually and tested quantitatively for the first time using an ASTM standard protocol. Results show that the PEMA/PVA coating not only delayed the initial period required for fog formation but also decreased the rate of light transmission decay. Finally, following a 24 hour immersion in water, these PEMA/PVA coatings remained stable and preserved their anti-fog properties.

  8. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU

    2009-01-01

    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  9. Anti-inflammatory and Anti-ulcerogenic Activities of Chantaleela Recipe

    OpenAIRE

    Sireeratawong, Seewaboon; Khonsung, Parirat; Piyabhan, Pritsana; Nanna, Urarat; Soonthornchareonnon, Noppamas; Jaijoy, Kanjana

    2012-01-01

    Chantaleela recipe is indicated for relieving fever in Thai traditional folk medicine. In the present study, Chantaleela recipe was investigated for anti-inflammatory, analgesic, antipyretic and anti-ulcerogenic activities. In preliminary investigation Chantaleela recipe was found to exert an inhibitory activity on the acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema as well as in carrageenan-induced hind paw edema in rats. The results suggest that the anti-infl...

  10. PRODUKSI ANTIBODI KUNING TELUR (IGY ANTI STREPTOCOCCUS MUTANS SEBAGAI ANTI KARIES GIGI

    Directory of Open Access Journals (Sweden)

    Okti Nadia Poetri

    2006-12-01

    Full Text Available The aim of this study was to explore IgY anti Streptococcus mutan production and the ability of Igy Streptococcus mutans blocking adhesion process. The eggs was collected from Single Comb Brown Leghorn which have been immunized by S. mutan. Agar gel precipitation test was done to detect IgY anti S. mutans in serum and egg. Egg which Countain IgY anti S. mutans was collected. IgY anti S. mutans extracted from egg yolk by mean s PEG-Amonium sulfat and purified using fast protein liquid chromatography. The purity of Igy anti S. mutans was determined by UV spectropometer. Biological activities of Igy anti S. mutans to inhibit adhession process was learned by anti adhesion test. We use two dose of IgY, which is 100 ug and 500 ug. Igy anti S. mutans formen in serum five weeks after the first immunization while it formed in egg nine weeks after the first immunization. Igy anti S. mutanss still present in serum andegg until twelve weeks from the first immunization. Igy anti S. mutanss could decrease the amount of bacteria which attach the epithelial cell surface. The amount of sticky bacteria on epithelial cell (without IgY are 40 cell bacteria/epithelial cell. After blocked by IgY anti S. mutanss the amount of bacteria turn into 30 cell bacteria/epithelial cell (for dose of 100 ug IgY and 28 cell bacteria/epitheelial cell (for dose of 500 ug IgY. This research concluded that hens were capable producing IgY anti S. mutanss in egg yolk and it can be used to solve dental caries problem which caused by S. mutanss.

  11. Anti Bacterial and Anti Inflammatory efficacy of Zingiber officinale and Decalepis hamiltonii ? In Vitro Study

    OpenAIRE

    Arun kumar M; Tejaswi B; Susila V Anand

    2014-01-01

    Aim: To evaluate the in vitro anti bacterial and anti inflammatory potential of Zingiber Officinale and Decalepis Hamiltonii against E. faecalis. Materials and Methods: Ethanolic extract of Zingiber and Decalepis was subjected to microbiological assay to determine its Maximum zone of inhibition using Agar disk diffusion test, minimum inhibitory concentration using serial broth dilution method and anti inflammatory potential using protein denaturation assay against E. faecalis. Results: Ethano...

  12. ANTI-B CELL THERAPY OF AUTOIMMUNE DISEASES

    Directory of Open Access Journals (Sweden)

    A. L. Masliansky

    2007-01-01

    Full Text Available Abstract. Our understanding of the multiple physiological and pathological functions of B-cells continues to expand at a fascinating rate. As pathogenic elements in the development of autoimmune diseases, B-cells have become the focus of new therapeutics. Based on the published data, rituximab, a chimeric monoclonal antibody to CD20, when used in combination with other agents (i.e., cyclophosphamide or methotrexate, appears to be a reasonable treatment option for refractory RA. There are now numerous case reports and small openlabel series using rituximab in many autoimmune diseases, others then RA. While these data must be interpreted with caution, they suggest that rituximab may be a promising addition to the therapeutic armamentarium in these diseases. However, additional controlled trials need to be conducted to confirm clinical efficacy, further define optimal dosage, response rates, comparative long-term efficacy, and treatment algorithm for rituximab in these patients.

  13. Resveratrol and related stilbenes: their anti-aging and anti-angiogenic properties.

    Science.gov (United States)

    Kasiotis, Konstantinos M; Pratsinis, Harris; Kletsas, Dimitris; Haroutounian, Serkos A

    2013-11-01

    Dietary stilbenes comprise a class of natural compounds that display significant biological activities of medicinal interest. Among them, their antioxidant, anti-aging and anti-angiogenesic properties are well established and subjects of numerous research endeavors. This mini-review aspires to account and present the literature reports published on research concerning various natural and synthetic stilbenes, such as trans-resveratrol. Special focus was given to most recent research findings, while the mechanisms underlying their anti-aging and anti-angiogenic effects as well as the respective signaling pathways involved were also presented and discussed.

  14. Dynamics of Anti-Proton -- Protons and Anti-Proton -- Nucleus Reactions

    CERN Document Server

    Galoyan, A; Uzhinsky, V

    2016-01-01

    A short review of simulation results of anti-proton-proton and anti-proton-nucleus interactions within the framework of Geant4 FTF (Fritiof) model is presented. The model uses the main assumptions of the Quark-Gluon-String Model or Dual Parton Model. The model assumes production and fragmentation of quark-anti-quark and diquark-anti-diquark strings in the mentioned interactions. Key ingredients of the model are cross sections of string creation processes and an usage of the LUND string fragmentation algorithm. They allow one to satisfactory describe a large set of experimental data, especially, a strange particle production, Lambda hyperons and K mesons.

  15. In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs.

    Science.gov (United States)

    El-Aarag, Bishoy Y A; Kasai, Tomonari; Zahran, Magdy A H; Zakhary, Nadia I; Shigehiro, Tsukasa; Sekhar, Sreeja C; Agwa, Hussein S; Mizutani, Akifumi; Murakami, Hiroshi; Kakuta, Hiroki; Seno, Masaharu

    2014-08-01

    Inhibition of angiogenesis is currently perceived as a promising strategy in the treatment of cancer. The anti-angiogenicity of thalidomide has inspired a second wave of research on this teratogenic drug. The present study aimed to investigate the anti-proliferative and anti-angiogenic activities of two thalidomide dithiocarbamate analogs by studying their anti-proliferative effects on human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cell lines. Their action on the expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 was also assessed. Furthermore, their effect on angiogenesis was evaluated through wound healing, migration, tube formation, and nitric oxide (NO) assays. Results illustrated that the proliferation of HUVECs and MDA-MB-231 cells was not significantly affected by thalidomide at 6.25-100μM. Thalidomide failed to block angiogenesis at similar concentrations. By contrast, thalidomide dithiocarbamate analogs exhibited significant anti-proliferative action on HUVECs and MDA-MB-231 cells without causing cytotoxicity and also showed powerful anti-angiogenicity in wound healing, migration, tube formation, and NO assays. Thalidomide analogs 1 and 2 demonstrated more potent activity to suppress expression levels of IL-6, IL-8, TNF-α, VEGF165, and MMP-2 than thalidomide. Analog 1 consistently, showed the highest potency and efficacy in all the assays. Taken together, our results support further development and evaluation of novel thalidomide analogs as anti-tumor and anti-angiogenic agents.

  16. Defining an "Anti" Stance: Key Pedagogical Questions about Engaging Anti-Racism in College Classrooms

    Science.gov (United States)

    Rebollo-Gil, Guillermo; Moras, Amanda

    2006-01-01

    This paper draws from social science literature on Whiteness and anti-racism as well as personal classroom experience to examine the obstacles educators face in teaching anti-racism to White college students. Emphasis is placed on popular perceptions and common definitions of the word "racism" as it is used in mainstream American society. The…

  17. Anti-microbial and anti-biofilm compounds from Indonesian medicinal plants

    NARCIS (Netherlands)

    Pratiwi, Sylvia U.T.

    2015-01-01

    Microbial biofilms causing elevated resistance to both most anti-microbial drugs and the host defense systems, which often results in persistent and difficult-to-treat infections. The discovery of anti-infective agents which are active against planktonic and biofilm microorganisms are therefore urge

  18. PREPARATION OF ANTI-IDIOTYPIC ANTIBODIES SPECIFIC FOR ANTI- HEL AND ANALYSIS OF THEIR FUNCTIONAL MIMICRY

    Institute of Scientific and Technical Information of China (English)

    李明远; 肖玉; 肖丽英; 李虹; 蒋中华; 牟家琬; 王道若

    2000-01-01

    Objective. This study is to investigate the functional mimicry by using anfi-idiotypic antibodies of enzymes. Methods. Monoclonal anti-idiotypic antibodies against anfi-HEL(hen egg-white lysozyme, HEL) antibodies were obtained by fusion of Sp2/0 myeloma ceils with spleen ceils of syngeneic mice immunized with monoclonal anti-HEL antibodies against HEL's different antigenic epitopes. Then bacteriolysis of the anti-idiotypic antibodies were ohserved. Results. Eight hybridomas strains secreting anti-idiotypic antibodies were observed and characterized. It was shown that two of eight anti-idiotypic antibodies secreted by two hybridomas( 1A10C9 and 2AllC1B3) could mimic HEL catalytic activity to lyse Micrococcus lysodeikticus and that the catalytic effect of mixed anti-idiotypic antibodies of 1A10 G9 and 2A11C1B3 was stronger than that of one of them, but less than HEL. Conclusion. The results demonstrated that the anti-idiotypic antibodies that could mimic enzyme activity existed in the idiotype network during anti-enzymatic immune response.

  19. Anti-cytokine biologic treatment beyond anti-TNF in Behçet's disease.

    Science.gov (United States)

    Arida, Aikaterini; Sfikakis, Petros P

    2014-01-01

    Unmet therapeutic needs in Behçet's disease have drawn recent attention to biological agents targeting cytokines other than TNF. The anti-IL-17 antibody secukinumab and the anti-IL-2 receptor antibody daclizumab were not superior to placebo for ocular Behçet's in randomised controlled trials, comprising 118 and 17 patients, respectively. The anti-IL-1 agents anakinra and canakinumab and the anti-IL-6 agent tocilizumab were given to isolated refractory disease patients, who were either anti-TNF naïve (n=9) or experienced (n=18). No new safety signals were reported. Although a potential for bias to report positive effects and underreport negative cases may exist, Anakinra was partially effective, whereas disease remission was noted after canakinumab in some anti-TNF resistant patients. Tocilizumab appeared effective for neuro-Behçet's, but not for mucocutaneous manifestations. Finally, in a pilot study of 7 patients with relapsing posterior uveitis refractory to azathioprine and/or cyclosporine, the anti-IL-1β antibody Gevokizumab was beneficial. Collectively, it seems that IL-1 and IL-6 are promising targets in patients refractory or intolerant to other regimens including anti-TNFs. However, controlled studies are surely needed.

  20. Tachyonic Anti-M2 Branes

    CERN Document Server

    Bena, Iosif; Kuperstein, Stanislav; Massai, Stefano

    2014-01-01

    We study the dynamics of anti-M2 branes in a warped Stenzel solution with M2 charges dissolved in fluxes by taking into account their full backreaction on the geometry. The resulting supergravity solution has a singular magnetic four-form flux in the near-brane region. We examine the possible resolution of this singularity via the polarization of anti-M2 branes into M5 branes, and compute the corresponding polarization potential for branes smeared on the finite-size four-sphere at the tip of the Stenzel space. We find that the potential has no minimum. We then use the potential for smeared branes to compute the one corresponding to a stack of localized anti-M2 branes, and use this potential to compute the force between two anti-M2 branes at tip of the Stenzel space. We find that this force, which is zero in the probe approximation, is in fact repulsive. This surprising result points to a tachyonic instability of anti-M2 branes in backgrounds with M2 brane charge dissolved in flux.

  1. Anti-damping effect of radiation reaction

    Science.gov (United States)

    Wang, G.; Li, H.; Shen, Y. F.; Yuan, X. Z.; Zi, J.

    2010-01-01

    The anti-damping effect of radiation reaction, which means the radiation reaction does non-negative work on a radiating charge, is investigated at length by using the Lorentz-Dirac equation (LDE) for the motion of a point charge respectively acted on by (a) a pure electric field, (b) a pure magnetic field and (c) the fields of an electromagnetic wave. We found that the curvature of the charge's trajectory plays an important role in the radiation reaction force, and the anti-damping effect cannot take place for the real macroscopic motions of a point charge. The condition for this anti-damping effect to take place is that the gradient of the external force field must exceed a certain value over the region of magnitude of the classical radius of massive charges (~10-15 m). Our results are potentially helpful to lessen the controversy on LDE and justify it as the correct classical equation describing the radiating charge's motion. If this anti-damping effect of LDE were a real existing physical process, it could serve as a mechanism within the context of classical electrodynamics for the stability of hydrogen atoms. Using the picture of an electron in quantum electrodynamics, namely the negative bare charge surrounded by the polarized positive charges of vacuum, we can obtain a reasonable explanation for the energy transferred to the electron during the occurrence of the anti-damping effect, on which the venerable work of Wheeler and Feynman has thrown some light.

  2. Anti-icing performance of superhydrophobic surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Farhadi, S.; Farzaneh, M. [CIGELE/INGIVRE, Department of Applied Sciences, Universite du Quebec a Chicoutimi, 555 University blvd., Saguenay, PQ, G7H 2B1 (Canada); Kulinich, S.A., E-mail: skulinic@uqac.ca [CIGELE/INGIVRE, Department of Applied Sciences, Universite du Quebec a Chicoutimi, 555 University blvd., Saguenay, PQ, G7H 2B1 (Canada)

    2011-05-01

    This article studies the anti-ice performance of several micro/nano-rough hydrophobic coatings with different surface chemistry and topography. The coatings were prepared by spin-coating or dip coating and used organosilane, fluoropolymer or silicone rubber as a top layer. Artificially created glaze ice, similar to the naturally accreted one, was deposited on the nanostructured surfaces by spraying supercooled water microdroplets (average size {approx}80 {mu}m) in a wind tunnel at subzero temperature (-10 deg. C). The ice adhesion strength was evaluated by spinning the samples in a centrifuge at constantly increasing speed until ice delamination occurred. The results show that the anti-icing properties of the tested materials deteriorate, as their surface asperities seem to be gradually broken during icing/de-icing cycles. Therefore, the durability of anti-icing properties appears to be an important point for further research. It is also shown that the anti-icing efficiency of the tested superhydrophobic surfaces is significantly lower in a humid atmosphere, as water condensation both on top and between surface asperities takes place, leading to high values of ice adhesion strength. This implies that superhydrophobic surfaces may not always be ice-phobic in the presence of humidity, which can limit their wide use as anti-icing materials.

  3. Anti-NMDA Receptor Encephalitis and Vaccination

    Science.gov (United States)

    Wang, Hsiuying

    2017-01-01

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint. PMID:28106787

  4. Anti-NMDA Receptor Encephalitis and Vaccination

    Directory of Open Access Journals (Sweden)

    Hsiuying Wang

    2017-01-01

    Full Text Available Anti-N-methyl-d-aspartate (Anti-NMDA receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  5. Anti-NMDA Receptor Encephalitis and Vaccination.

    Science.gov (United States)

    Wang, Hsiuying

    2017-01-18

    Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.

  6. Clinical Scenarios for Discordant Anti-Xa

    Science.gov (United States)

    Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

  7. Clinical Scenarios for Discordant Anti-Xa

    Directory of Open Access Journals (Sweden)

    Jesus Vera-Aguilera

    2016-01-01

    Full Text Available Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.

  8. National Anti-Piracy Organisation Established in China

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    On 25 October 2002,the first national anti-piracyorganisation-the Anti-Piracy Committee of the ChinaCopyright Association was established,which consists of 82members representing all the regional and sectorial anti-piracyorganisations throughout China.The Anti-Piracy Committee will be responsible for thecoordination of the regional and sectorial anti-piracyorganisations nationwide,cooperate with the copyright

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

    Science.gov (United States)

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

    2015-04-01

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

  10. EVALUATION OF ANTI-NOCICEPTIVE AND ANTI-INFLAMMATORY ACTIVITY OF PUNICA GRANATUM SEED EXTRACT

    Directory of Open Access Journals (Sweden)

    Gupta Jeetendra Kumar

    2011-12-01

    Full Text Available The plant Punica granatum of family Punicaceae is distributed throughout India and reputed to have numerous applications in traditional medicine system. In order to justify its folkloric use in nociception and inflammation, the study was performed.In this study, the extraction of Punica granatum seed extract was carried out in aqueous media. In order to explore its potency, various experimental models of anti-nociceptive and anti-inflammatory activities were taken. The oral administration of the extract 100mg and 200mg per kg body weight showed significant pharmacological action. Furthermore the anti-ulcer activity was carried out with the help of Indomethacin induced ulceration model using Mesoprostol as standard drug and it showed no ulcerogenic effect in wistar albino rats.Overall, the extract was found to be significant anti-nociceptive and anti-inflammatory activity with no ulcerogenic adverse effect.

  11. Data of evolutionary structure change: 1ANTI-2HIJL [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ANTI-2HIJL 1ANT 2HIJ I L ------RD---IPMNPMCIYRSPEKKATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFAMTKLGACNDTLQQLMEVFKFDTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFGDKSLTFNETYQDISE...> 1ANT I 1ANTI AASTA...dbID> I 1ANTI IPMNPMCIYRS 1ANT I 1ANTI RSPEKKATNRRVWI 1ANTI RSLNPNRVTFK

  12. Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity

    Institute of Scientific and Technical Information of China (English)

    Yong HUANG; Yu SHEN; Ying FENG; Lin CAO; Ying LENG

    2005-01-01

    Aim: To investigate the anti-implantation effect of droloxifene and study the possible relationship between the anti-estrogenic activity of droloxifene and its antiimplantation effect. Methods: Pregnant rats were treated orally with droloxifene at 10:00 AM on d 2 at doses of 1.25-20 mg/kg to observe anti-implantation effects,and then doses of 14 mg/kg or 2.5 mg/kg were given at different time on d 2 to d 5to determine the optimal administration time for anti-implantation effects. Pregnant rats were treated with a combination of droloxifene (2.5 mg/kg, ig) and E2 (0.5-8.0 μg/kg, sc) on the optimal administration time to observe the antagonistic effect of external estrogen on the anti-implantation effect of droloxmene. Serum estrogen and progesterone levels were measured by carrying out radioimmunoas says on d 1 to d 6 in droloxifene-treated and control rats to determine the surge time for nidatory estrogen and the effect of droloxifene on ovary function. Results:Droloxifene has anti-implantation effects in rats. The optimal oral administration time was at 22:00 PM on d 4, which was after the surge time for nidatory estrogen (on d 4 at 10:00 AM). This suggests that the anti-implantation effect of droloxifene is not attributable to antagonism of the surge in secretion of nidatory estrogen.External estrogen did not antagonize the anti-implantation effect of droloxifene.Droloxifene had no effect on the serum levels of estrogen and progesterone on d 5 or d 6 when administered on d 4 at 22:00 PM. Conclusion: Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.

  13. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    Specific inhibition of the cytokine, tumor necrosis factor-α (TNF), has revolutionized the treatment of patients with several autoimmune diseases, and genetically engineered anti-TNF antibody constructs now constitute a heavy medicinal expenditure in many countries. Unfortunately, up to 30......% of patients do not respond and about 50% of those who do loose response with time. Furthermore, safety may be compromised by immunogenicity with the induction of anti-drug-antibodies (ADA). Assessment of drug pharmacokinetics and ADA is increasingly recognized as a requirement for safe and rational use...... of protein drugs. The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response. The objective of the present...

  14. Anti-Americanism in Contemporary Indonesia

    Directory of Open Access Journals (Sweden)

    Saiful Mujani

    2005-08-01

    Full Text Available This paper attempts to explore these two basic arguments. To that end we need first to discuss what is meant by "anti-Americanism," then what is meant by "unjust American foreign policies," and thirdly what is meant by "civilization" in the context of Indonesian Muslim society. "Anti-Americanism" in the international context is an individual or group attitude or action that reflects a feeling of dislike, hatred or intolerance toward America as a nation, or America as defined by the attitudes or behavior of the American government toward other countries. It is not easy to decide how to measure these anti-American attitudes or actions.Copyright (c 2014 by SDI. All right reserved.DOI: 10.15408/sdi.v12i2.588

  15. Deicing and Anti-Icing Unite

    Science.gov (United States)

    2002-01-01

    With funding from Glenn's Small Business Innovation Research (SBIR) program, Cox & Company, Inc., built an ice protection system that combines thermal anti-icing and mechanical deicing to keep airfoils (wings and other lifting surfaces) clear of ice. Cox's concept was to combine an anti-icing system with NASA's Electro-Mechanical Expulsion Deicing System, a mechanical deicer. The anti-icing element of this hybrid would reduce the aerodynamic losses associated with deicing systems. The Cox Low Power Ice Protection System is the first new aircraft ice protection system that has been approved by the Federal Aviation Administration for use on a business jet in 40 years. While the system is currently sized for Premier class aircraft, there are no apparent constraints prohibiting its use on aircraft of any size. The company is investigating further applications, such as adapting the system for unmanned aerial vehicles and other military aircraft.

  16. Observations on fluxes near anti-branes

    CERN Document Server

    Cohen-Maldonado, Diego; Van Riet, Thomas; Vercnocke, Bert

    2015-01-01

    We revisit necessary conditions for gluing local (anti)-D3 throats into flux throats with opposite charge. These consistency conditions typically reveal singularities in the 3-form fluxes whose meaning is being debated. In this note we prove, under well-motivated assumptions, that singularities remain even when the anti-D3 branes are puffed up into spherical NS5 branes. It does not seem possible to ascribe the singular flux to the self-energy of the 5-branes but rather to the singular clumping of the background fluxes. We furthermore comment on the gluing conditions at finite temperature and point out that one specific assumption of a recent no-go theorem can be broken if anti-branes are to polarise into spherical NS5 branes at zero temperature. Our first result, however, casts some doubt on whether this gap in the no-go theorem can be successfully employed to construct finite temperature solutions.

  17. Anti-integrin therapy for multiple sclerosis.

    Science.gov (United States)

    Kawamoto, Eiji; Nakahashi, Susumu; Okamoto, Takayuki; Imai, Hiroshi; Shimaoka, Motomu

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  18. Anti-Integrin Therapy for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Eiji Kawamoto

    2012-01-01

    Full Text Available Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  19. What is an anti-aging treatment?

    Science.gov (United States)

    Gems, David

    2014-10-01

    Key objectives of biogerontology are to understand the biology of aging and to translate scientific insight into interventions that improve late-life health - or anti-aging treatments. In this context, when considering the problem of how to effect translational research, it is useful to have a clear, consensus view on what exactly constitutes an anti-aging treatment. This essay critically assesses the understanding of this concept common among biogerontologists, and proposes a new definition. A current conception of anti-aging treatment imagines a primary cause of aging that is causally upstream of, and the cause of, all age-related pathology. Intervening in this aging process thus protects against the totality of age-related diseases. However, this underlying aging process remains an abstraction. By contrast, what is demonstrable is that interventions in model organisms can improve late-life health and extend lifespan. Furthermore, a safe deduction is that treatments that extend lifespan do so by reducing age-related pathology, both florid and subtle. What is currently identifiable about aging (i.e. senescence) is that it is a very complex disease syndrome, likely involving a number of biological mechanisms. Treatments that substantially extend lifespan must suppress multiple pathologies that otherwise limit lifespan, but whether they suppress the entire aging process remains undemonstrated. A more pragmatic and realistic definition of anti-aging treatment is any preventative approach to reduce late-life pathology, based on the understanding that senescence is a disease syndrome. This definition would encompass preventative approaches aimed at both broad and narrow spectra of age-related pathologies. Its adoption would facilitate translation, since it would shift the emphasis to medical practice, particularly the introduction of preventative approaches. Narrow spectrum anti-aging treatments (e.g. the cardiovascular polypill) could establish a practice that

  20. Systematic review: new serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes.

    Science.gov (United States)

    Bonneau, J; Dumestre-Perard, C; Rinaudo-Gaujous, M; Genin, C; Sparrow, M; Roblin, X; Paul, S

    2015-03-01

    Traditionally, IBD diagnosis is based on clinical, radiological, endoscopic, and histological criteria. Biomarkers are needed in cases of uncertain diagnosis, or to predict disease course and therapeutic response. No guideline recommends the detection of antibodies (including ASCA and ANCA) for diagnosis or prognosis of IBD to date. However, many recent data suggest the potential role of new serological markers (anti-glycan (ACCA, ALCA, AMCA, anti-L and anti-C), anti-GP2 and anti-GM-CSF Ab). This review focuses on clinical utility of these new serological markers in diagnosis, prognosis and therapeutic monitoring of IBD. Literature review of anti-glycan, anti-GP2 and anti-GM-CSF Ab and their impact on diagnosis, prognosis and prediction of therapeutic response was performed in PubMed/MEDLINE up to June 2014. Anti-glycan, anti-GP2 and anti-GM-CSF Ab are especially associated with CD and seem to be correlated with complicated disease phenotypes even if results differ between studies. Although anti-glycan Ab and anti-GP2 Ab have low sensitivity in diagnosis of IBD, they could identify a small number of CD patients not detected by other tests such as ASCA. Anti-glycan Abs are associated with a progression to a more severe disease course and a higher risk for IBD-related surgery. Anti-GP2 Ab could particularly contribute to better stratify cases of pouchitis. Anti-GM-CSF Ab seems to be correlated with disease activity and could help predict relapses. These new promising biomarkers could particularly be useful in stratification of patients according to disease phenotype and risk of complications. They could be a valuable aid in prediction of disease course and therapeutic response but more prospective studies are needed.

  1. Anti-atherosclerotic effects of konjac

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2015-04-01

    Full Text Available Definition: The Konjac plant comes from the genus Amorphophallus. Japanese food uses Konjac cake. Konjac contains almost no calories and a great amount of dietary fiber. Here, we reviewed possible anti-atherosclerotic effects of konjac, using the search Pubmed ®. Konjac ingestion is likely beneficially associated with obesity, blood pressure, lipid and glucose metabolism. However, evidence is lacking on the relationship between konjac ingestion and development of atherosclerotic diseases. To more fully understand the anti-atherosclerotic effects of konjac, future studies, preferably with larger numbers of subjects, will be performed.

  2. Aspherical photon and anti-photon surfaces

    Directory of Open Access Journals (Sweden)

    G.W. Gibbons

    2016-12-01

    Full Text Available In this note we identify photon surfaces and anti-photon surfaces in some physically interesting spacetimes, which are not spherically symmetric. All of our examples solve physically reasonable field equations, including for some cases the vacuum Einstein equations, albeit they are not asymptotically flat. Our examples include the vacuum C-metric, the Melvin solution of Einstein–Maxwell theory and generalisations including dilaton fields. The (anti-photon surfaces are not round spheres, and the lapse function is not always constant.

  3. Anti-Inflammatory Activity of Natural Products

    Directory of Open Access Journals (Sweden)

    Abdullatif Azab

    2016-10-01

    Full Text Available This article presents highlights of the published literature regarding the anti-inflammatory activities of natural products. Many review articles were published in this regard, however, most of them have presented this important issue from a regional, limited perspective. This paper summarizes the vast range of review and research articles that have reported on the anti-inflammatory effects of extracts and/or pure compounds derived from natural products. Moreover, this review pinpoints some interesting traditionally used medicinal plants that were not investigated yet.

  4. Overview of Anti-tank Mines

    Institute of Scientific and Technical Information of China (English)

    Manfred Held

    2006-01-01

    First the different anti-tank mines laying possibilities are shortly summarized: hand emplaced, with mine layers, ground or helicopter relatively topographical well defined, and with cluster systems of projectiles, rockets and aircraft dispensers. Then examples of the three generations of anti-tank mines are presented:Ⅰ generation: detonating only beneath the track; Ⅱ generation: detonating beneath the track and belly;Ⅲ generation: mines with off-route actions. Weight and cost comparisons are strongly favoring the off-route Ⅲ-generation mines.

  5. Characterization of subpopulation lacking both B-cell and plasma cell markers in Waldenstrom macroglobulinemia cell line.

    Science.gov (United States)

    Wada, Naoki; Zhan, Maosheng; Hori, Yumiko; Honma, Keiichiro; Ikeda, Jun-ichiro; Morii, Eiichi

    2014-01-01

    Cancer cells with tumorigenic potential are limited to a small population known as cancer-initiating cells (CICs). To date, CICs have not been identified in non-Hodgkin's lymphomas. Here, we investigated a candidate of CICs of an indolent non-Hodgkin's lymphoma, Waldenstrom macroglobulinemia (WM), using WM cell line MWCL-1. WM tumor expresses both B-cell and plasma cell markers, CD20 and CD138. When stained with anti-CD20 and anti-CD138 antibodies, MWCL-1 cells were classified into three subpopulations: CD20⁻ CD138⁻, CD20⁺ CD138⁻, and CD20⁺ CD138⁺. When cultured, CD20⁻ CD138⁻ cells yielded all three subpopulations, but CD20⁺ cells did not yield CD20⁻ CD138⁻ cells. Higher reactive oxygen species (ROS) expelling and in vitro colony formation activities were detected in CD20⁻ CD138⁻ cells than in CD20⁺ CD138⁻ and CD20⁺ CD138⁺ cells. When cultured in the absence of serum or with anti-cancer drug, CD20⁻ CD138⁻ cells were resistant to apoptosis. In contrast, CD20⁺ CD138⁺ cells were vulnerable to apoptosis in the same condition. In fact, the immunohistochemical analysis with clinical samples revealed that tumor cells in apoptosis were CD138-positive. The production of all three subpopulations, the efficient ROS expelling and in vitro colony-forming activities, and the resistance to apoptosis suggested that the CD20⁻ CD138⁻ cell might be a candidate of CICs in WM.

  6. Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review

    Directory of Open Access Journals (Sweden)

    Piacente S

    2006-03-01

    Full Text Available Abstract Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E. These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS, which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

  7. Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications.

    Science.gov (United States)

    Virella, G; Hyman, B

    1991-01-01

    We have developed enzymoimmunoassays (EIA) for the quantitation of antibodies (Ab) to tetanus and diphtheria toxoids (TT, DT) using Immulon I plates coated with the appropriate toxoid. A preparation of human tetanus immunoglobulin with a known concentration of anti-TT Ab was used as calibrator of the anti-TT antibody assay. The assay of anti-DT Ab is calibrated with a pool of human sera whose anti-DT Ab concentration was determined by quantitative immunoelectrophoresis, using a horse anti-DT with known Ab concentration as calibrator. A peroxidase-conjugated anti-human IgG was used in both assays. ABTS was used as substrate, and the reaction was stopped after 1 min incubation with citric acid and the OD measured at 414 nm on a Vmax reader. The assays have been applied to a variety of clinical situations. In patients suspected of having tetanus, the quantitation of antibodies has been helpful in establishing a diagnosis. In patients with a history of hypersensitivity to tetanus toxoid, verification of the levels of anti-TT antibody may prevent unnecessary and potentially harmful immunizations. The assays have also been used for the diagnostic evaluation of the humoral immune response to TT and DT, both in pediatric patients and in immunosuppressed patients. Several non-responders have been detected, and we have recently used the assay to monitor the effects of fish oil administration on the humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. ANTI-MICROBIAL AND ANTI-AMOEBIC ACTIVITY SOME AZOMETHINES - POTENTIAL TEXTILE DYESTUFFS

    Directory of Open Access Journals (Sweden)

    DJORDJEVIC Dragan

    2016-05-01

    Full Text Available In this paper, new synthesized three azomethine derivatives applied in dyeing textiles checking the anti-microbial properties of active components, at the same time [1-3]. The emphasis is thrown on the verification of anti-microbial properties that are important for obtaining textile with significantly improved performance. All compounds were characterized and evaluated for their anti-microbial activity against 7 pathogenic bacteria, 1 parasitic protozoan and 1 fungus. It estimated anti-bacterial activity in vitro against the following microorganisms Staphylococcus aureus, Bacillus anthracis, Streptococcus faecalis, Enterobacter sp., Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Candida albicans. The anti-amoebic activity in vitro was evaluated against the HM1: IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The synthesized azomethines, showed very good substantivity for wool fibers, gave fine coloring, with good degree of exhaustion after dyeing. The combination of extended synthetic analogues of natural molecules leads to discovery of chemical entities which might be excellent anti-microbial and anti-amoebic compounds as depicted in our results. Being highly the effects this compound can be explored in future as an option for decreasing pathogenic potential of infecting from different sources. Azomethines containing hydrazone (dyestuff 1 and phenylhydrazone (dyestuff 2 as moiety show average yield and moderate inhibition activity while azomethines containing thiosemicarbazone (dyestuff 3 as moiety show higher yield and greater inhibition activity towards gram-negative and gram-positive bacteria as well as a fungus.

  9. Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

    CERN Document Server

    Chekanov, S; Magill, S; Musgrave, B; Nicholass, D; Repond, J; Yoshida, R; Mattingly, M C K; Jechow, M; Pavel, N; Yagues-Molina, A G; Antonelli, S; Antonioli, P; Bari, G; Basile, M; Bellagamba, L; Bindi, M; Boscherini, D; Bruni, A; Bruni, G; Cifarelli, L; Cindolo, F; Contin, A; Corradi, M; De Pasquale, S; Iacobucci, G; Margotti, A; Nania, R; Polini, A; Sartorelli, G; Zichichi, A; Bartsch, D; Brock, I; Goers, S; Hartmann, H; Hilger, E; Jakob, H P; Jüngst, M; Kind, O M; Nuncio-Quiroz, A E; Paul, E; Renner, R; Samson, U; Schonberg, V; Shehzadi, R; Wlasenko, M; Brook, N H; Heath, G P; Morris, J D; Namsoo, T; Capua, M; Fazio, S; Mastroberardino, A; Schioppa, M; Susinno, G; Tassi, E; Kim, J Y; Ma, K J; Ibrahim, Z A; Kamaluddin, B; Wan-Abdullah, W A T; Ning, Y; Ren, Z; Sciulli, F; Chwastowski, J; Eskreys, A; Figiel, J; Galas, A; Gil, M; Olkiewicz, K; Stopa, P; Zawiejski, L; Adamczyk, L; Bold, T; Grabowska-Bold, I; Kisielewska, D; Lukasik, J; Przybycien, M; Suszycki, L; Kotanski, A; Slominski, W; Adler, V; Behrens, U; Bloch, I; Blohm, C; Bonato, A; Borras, K; Ciesielski, R; Coppola, N; Dossanov, A; Drugakov, V; Fourletova, J; Geiser, A; Gladkov, D; Göttlicher, P; Grebenyuk, J; Gregor, I; Haas, T; Hain, W; Horn, C; Huttmann, A; Kahle, B; Katkov, I I; Klein, U; Kötz, U; Kowalski, H; Lobodzinska, E; Löhr, B; Mankel, R; Melzer-Pellmann, I A; Miglioranzi, S; Montanari, A; Notz, D; Rinaldi, L; Roloff, P; Rubinsky, I; Santamarta, R; Schneekloth, U; Spiridonov, A; Stadie, H; Szuba, D; Szuba, J; Theedt, T; Wolf, G; Wrona, K; Youngman, C; Zeuner, W; Lohmann, W; Schlenstedt, S; Barbagli, G; Gallo, E; Pelfer, P G; Bamberger, A; Dobur, D; Karstens, F; Vlasov, N N; Bussey, P J; Doyle, A T; Dunne, W; Ferrando, J; Forrest, M; Saxon, D H; Skillicorn, I O; Gialas, I; Papageorgiu, K; Gosau, T; Holm, U; Klanner, R; Lohrmann, E; Salehi, H; Schleper, P; Schörner-Sadenius, T; Sztuk, J; Wichmann, K; Wick, K; Foudas, C; Fry, C; Long, K R; Tapper, A D; Kataoka, M; Matsumoto, T; Nagano, K; Tokushuku, K; Yamada, S; Yamazaki, Y; Barakbaev, A N; Boos, E G; Pokrovskiy, N S; Zhautykov, B O; Aushev, V; Son, D; De Favereau, J; Piotrzkowski, K; Barreiro, F; Glasman, C; Jiménez, M; Labarga, L; Del Peso, J; Ron, E; Soares, M; Terron, J; Zambrana, M; Corriveau, F; Liu, C; Walsh, R; Zhou, C; Tsurugai, T; Antonov, A; Dolgoshein, B A; Sosnovtsev, V; Stifutkin, A; Suchkov, S; Dementiev, R K; Ermolov, P F; Gladilin, L K; Khein, L A; Korzhavina, I A; Kuzmin, V A; Levchenko, B B; Lukina, O Yu; Proskuryakov, A S; Shcheglova, L M; Zotkin, D S; Zotkin, S A; Abt, I; Büttner, C; Caldwell, A; Kollar, D; Schmidke, W B; Sutiak, J; Grigorescu, G; Keramidas, A; Koffeman, E; Kooijman, P; Pellegrino, A; Tiecke, H; Vázquez, M; Wiggers, L; Brümmer, N; Bylsma, B; Durkin, L S; Lee, A; Ling, T Y; Allfrey, P D; Bell, M A; Cooper-Sarkar, A M; Cottrell, A; Devenish, R C E; Foster, B; Korcsak-Gorzo, K; Patel, S; Roberfroid, V; Robertson, A; Straub, P B; Uribe-, C; Estrada; Walczak, R; Bellan, P; Bertolin, A; Brugnera, R; Carlin, R; Dal Corso, F; Dusini, S; Garfagnini, A; Limentani, S; Longhin, A; Stanco, L; Turcato, M; Oh, B Y; Raval, A; Ukleja, J; Whitmore, J J; Iga, Y; D'Agostini, G; Marini, G; Nigro, A; Cole, J E; Hart, J C; Abramowicz, H; Gabareen, A; Ingbir, R; Kananov, S; Levy, A; Kuze, M; Maeda, J; Hori, R; Kagawa, S; Okazaki, N; Shimizu, S; Tawara, T; Hamatsu, R; Kaji, H; Kitamura, S; Ota, O; Ri, Y D; Ferrero, M I; Monaco, V; Sacchi, R; Solano, A; Arneodo, M; Ruspa, M; Fourletov, S; Martin, J F; Boutle, S K; Butterworth, J M; Gwenlan, C; Jones, T W; Loizides, J H; Sutton, M R; Wing, M; Brzozowska, B; Ciborowski, J; Grzelak, G; Kulinski, P; Luzniak, P; Malka, J; Nowak, R J; Pawlak, J M; Tymieniecka, T; Ukleja, A; Zarnecki, A F; Adamus, M; Plucinsky, P P; Eisenberg, Y; Giller, I; Hochman, D; Karshon, U; Rosin, M; Brownson, E; Danielson, T; Everett, A; Kcira, D; Reeder, D D; Ryan, P; Savin, A A; Smith, W H; Wolfe, H; Bhadra, S; Catterall, C D; Cui, Y; Hartner, G; Menary, S; Noor, U; Standage, J; Whyte, J

    2007-01-01

    The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV using an integrated luminosity of 120 pb-1. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements.

  10. Anti-beta2 glycoprotein 1 and the anti-phospholipid syndrome.

    LENUS (Irish Health Repository)

    Keane, Pearse A

    2012-02-03

    PURPOSE: To describe a patient who presented with bilateral retinal vascular occlusion and the use of anti-beta2 glycoprotein 1 (GPI) antibody testing in the diagnosis of antiphospholipid syndrome. DESIGN: Observational case report. METHODS: Hematological investigations were performed on a 49-year-old man who presented with rapid onset of bilateral severe central retinal vein occlusion. RESULTS: Lupus anticoagulant and anticardiolipin antibody testing was negative. Markedly raised titers of anti-beta2 GPI antibodies were detected on two separate occasions. CONCLUSIONS: The raised titers of anti-beta2 GPI antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome.

  11. Predictive Mapping of Anti-Social Behaviour

    NARCIS (Netherlands)

    Smit, S.K.; Vecht, B. van der; Lebesque, L.H.E.M.

    2014-01-01

    Predictive mapping of crime and anti-social behaviour is becoming more and more popular as a tool to support police and policy makers. Important ingredients of such models are often demographic and economic characteristics of the area. Since those are hard to influence, we propose to use the environ

  12. Anti-tubercular agents from Glycyrrhiza glabra.

    Science.gov (United States)

    Kalani, Komal; Chaturvedi, Vinita; Alam, Sarfaraz; Khan, Feroz; Srivastava, Santosh Kumar

    2015-01-01

    Bioactivity guided isolation of Glycyrrhiza glabra (Leguminosae / Fabaceae) roots resulted in the characterization of 18β-glycyrrhetinic acid as a major anti-tubercular agent. Further, GA-1 was semi-synthetically converted into its nine derivatives, which were in-vitro evaluated for their antitubercular potential against Mycobacterium tuberculosis H37Rv using BACTEC-460 radiometric susceptibility assay. All the derivatives were active, but the benzylamide (GA-8, MIC 12.5μg/ml) and ethyl oxylate (GA-3, MIC 25.0 μg/ml) derivatives were significantly active against the pathogen. This was further supported by the molecular docking studies, which showed adequate docking (LibDock) scores for GA-3 (120.3) and GA-8 (112.6) with respect to the standard anti-tubercular drug, rifampicin (92.94) on the DNA-directed RNA polymerase subunit beta (rpoB) target site. Finally, the in silico pharmacokinetic and drug-likeness studies showed that GA-3 and GA- 8 possesses drug-like properties. This is the first ever report on the anti-tubercular potential of GA and its derivatives. These results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non toxic natural product.

  13. Anti-inflammatory activity of Taraxacum officinale.

    Science.gov (United States)

    Jeon, Hye-Jin; Kang, Hyun-Jung; Jung, Hyun-Joo; Kang, Young-Sook; Lim, Chang-Jin; Kim, Young-Myeong; Park, Eun-Hee

    2008-01-04

    Taraxacum officinale has been widely used as a folkloric medicine for the treatment of diverse diseases. The dried plant was extracted with 70% ethanol to generate its ethanol extract (TEE). For some experiments, ethyl acetate (EA), n-butanol (BuOH) and aqueous (Aq) fractions were prepared in succession from TEE. TEE showed a scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, a diminishing effect on intracellular reactive oxygen species (ROS) level, and an anti-angiogenic activity in the chicken chorioallantoic (CAM) assay. In the carrageenan-induced air pouch model, TEE inhibited production of exudate, and significantly diminished nitric oxide (NO) and leukocyte levels in the exudate. It also possessed an inhibitory effect on acetic acid-induced vascular permeability and caused a dose-dependent inhibition on acetic acid-induced abdominal writhing in mice. Suppressive effects of TEE on the production of NO and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated macrophages were also assessed. Among the fractions, the n-butanol fraction (BuOH) was identified to be most effective in the CAM assay. Collectively, Taraxacum officinale contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities through its inhibition of NO production and COX-2 expression and/or its antioxidative activity.

  14. The Anti-Social Activities Attitude Scale.

    Science.gov (United States)

    Ribner, Sol; Chein, Isidor

    1979-01-01

    This article presents reliability and validity evidence on the Anti-Social Activities Attitude Scale. The scale is not intended to predict individual behavior but to assess the moral climate within a population as supportive or restrictive of antisocial acts. The scale itself is included. (SJL)

  15. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

    This thesis focuses on the disorder we know as schizophrenia. Although there is treatment for schizophrenia in the form of anti-psychotic drugs, not all patients respond well to this treatment. A large part of patients will have remaining symptoms for the rest of their lives. A number of hypotheses

  16. Centauro- and anti-Centauro-type events

    CERN Document Server

    Martinis, M; Martinis, M; Mikuta-Martinis, V

    1994-01-01

    Assuming that leading particles in high-energy hadronic and nuclear collisions become sources of a classical pion field, we show that the direct production of pions favors Centauro ( mainly charged ) events and that the production of pions through the \\rho-type channel favors anti-Centauro ( mainly neutral ) events. We also observe a strong negative neutral-charged correlation in both cases.

  17. Anti-forensics of chromatic aberration

    Science.gov (United States)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  18. Anti-C1q autoantibodies

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this co

  19. Methods for predicting anti-cancer response

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to methods for predicting response of a cancer in a subject to anti-cancer therapies based upon a determination and analysis of a chromosomal aberration score, such as the number of allelic imbalance or the number of telomeric allelic imbalance in the chromosomes...

  20. Anti-early pregnancy by PDT

    Science.gov (United States)

    Ding, Ai-Hua; Chen, Hui-Ling

    1993-03-01

    The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

  1. Anti-inflammatory drug therapy in asthma

    NARCIS (Netherlands)

    Rottier, Bart L.; Duiverman, Eric J.

    2009-01-01

    Asthma is a disease with chronic inflammation of the airways and and-inflammatory treatment is a logical treatment. Inhaled corticosteroids [ICS] remain the cornerstone of anti-inflammatory therapy in recent international guidelines. Asthma cannot be cured by any medication: if the drug is discontin

  2. Quantum Zeno and anti-Zeno paradoxes

    Indian Academy of Sciences (India)

    S M Roy

    2001-02-01

    Continuous observation of a time independent projection operator is known to prevent change of state (the quantum Zeno paradox). We discuss the recent result that generic continuous measurement of time dependent projection operators will in fact ensure change of state: an anti-Zeno paradox.

  3. ANTI INFLAMMATORY ACTIVITY OF MORINGA OLIEFERA. LAM

    OpenAIRE

    1999-01-01

    The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P

  4. Utopian Education and Anti-Utopian Anthropology

    Science.gov (United States)

    Papastephanou, Marianna

    2013-01-01

    This article explores the connection of education, utopia and anthropology, aiming to tease out some educational implications of anti-utopian anthropological essentialism and to show why these should be staved off. It will be shown how an anthropology that tarnishes human nature operates and how it affects educational intervention in the shaping…

  5. Cultural Diversity and Anti-Poverty Policy

    Science.gov (United States)

    Lamont, Michele; Small, Mario Luis

    2010-01-01

    This article examines how anti-poverty policy has considered the role of culture and how it ought to do so. While some have explained poverty as a function of the presumed cultural deficiency or distinctiveness of the poor, we suggest that these explanations have not been convincing and that policy requires a broader and more sophisticated…

  6. Anti-Luck (Too Weak) Virtue Epistemology

    DEFF Research Database (Denmark)

    Broncano-Berrocal, Fernando

    2014-01-01

    I argue that Duncan Pritchard’s anti-luck virtue epistemology is insufficient for knowledge. I show that Pritchard fails to achieve the aim that motivates his adoption of a virtue-theoretic condition in the first place: to guarantee the appropriate direction of fit that known beliefs have. Finally...

  7. Anti-inflammatory effect of (+)-pinitol.

    Science.gov (United States)

    Singh, R K; Pandey, B L; Tripathi, M; Pandey, V B

    2001-02-01

    In the carrageenin-induced paw oedema in rats, (+)-pinitol (2.5-10 mg/kg, i.p.), isolated from Abies pindrow leaves, showed a significant anti-inflammatory effect, the highest dose being comparable to phenylbutazone (100 mg/kg, i.p.).

  8. Anti-TNFa treatment in rheumatoid arthritis

    NARCIS (Netherlands)

    Broeder, Alfonso Abigaël den

    2001-01-01

    De behandeling van reumatoide artritis (RA) is de laatste jaren in een stroomversnelling geraakt door de ontwikkeling van nieuwe geavanceerde medicijnen. De meest veelbelovende exponent van deze ontwikkeling is de groep medicijnen die bekend staan als TNF blokkerende middelen (anti-TNF). Deze medici

  9. Guideline for radioimmunotherapy of CD20{sup +} follicular B-cell non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, M.; Gruenwald, F.; Knapp, W.H. [Deutsche Gesellschaft fuer Nuklearmedizin, Kassel (Germany); Truemper, L.; Schilling, C. v.; Dreyling, M. [Deutsche Gesellschaft fuer Haematologie und Onkologie, Kassel (Germany)

    2009-07-01

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmuno-therapy under consideration of the development of the disease. (orig.)

  10. Anti-damping effect of radiation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G; Yuan, X Z [School of Physics and Electric Information, Wenzhou University, Wenzhou 325035 (China); Li, H [Department of Physics, Yantai University, Yantai 264005 (China); Shen, Y F [Department of Physics, China University of Mining and Technology, Xuzhou 221008 (China); Zi, J [National Laboratory of Surface Physics, Fudan University, Shanghai 200433 (China)], E-mail: gz_wang131@yahoo.cn

    2010-01-15

    The anti-damping effect of radiation reaction, which means the radiation reaction does non-negative work on a radiating charge, is investigated at length by using the Lorentz-Dirac equation (LDE) for the motion of a point charge respectively acted on by (a) a pure electric field, (b) a pure magnetic field and (c) the fields of an electromagnetic wave. We found that the curvature of the charge's trajectory plays an important role in the radiation reaction force, and the anti-damping effect cannot take place for the real macroscopic motions of a point charge. The condition for this anti-damping effect to take place is that the gradient of the external force field must exceed a certain value over the region of magnitude of the classical radius of massive charges ({approx}10{sup -15} m). Our results are potentially helpful to lessen the controversy on LDE and justify it as the correct classical equation describing the radiating charge's motion. If this anti-damping effect of LDE were a real existing physical process, it could serve as a mechanism within the context of classical electrodynamics for the stability of hydrogen atoms. Using the picture of an electron in quantum electrodynamics, namely the negative bare charge surrounded by the polarized positive charges of vacuum, we can obtain a reasonable explanation for the energy transferred to the electron during the occurrence of the anti-damping effect, on which the venerable work of Wheeler and Feynman has thrown some light.

  11. Anti-HLA and Anti-MICA Antibodies in Liver Transplant Recipients: Effect on Long-Term Graft Survival

    Directory of Open Access Journals (Sweden)

    Michał Ciszek

    2013-01-01

    Full Text Available Objective. Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival. Methods. Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II and MICA antibodies using Luminex assays. Results. There were 32 (26% patients with positive anti-HLA and 37 (30% with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23% in anti-HLA positive group compared to 20 (22% in anti-HLA negative group ( and in 8 cases (22% in anti-MICA positive group but 19 (23% in anti-MICA negative group (. No correlations were detected between presence of antibodies and acute graft rejection (AGR. Presence of any antibodies (anti-HLA or anti-MICA antibodies correlated with late graft rejection (. Conclusion. Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection.

  12. Anti-Oxidant, Anti-Aging, and Anti-Melanogenic Properties of the Essential Oils from Two Varieties of Alpinia zerumbet.

    Science.gov (United States)

    Tu, Pham Thi Be; Tawata, Shinkichi

    2015-09-14

    Here, we investigated the anti-oxidant and anti-aging effects of essential oils (EOs) from the leaves of Alpinia zerumbet (tairin and shima) in vitro and anti-melanogenic effects in B16F10 melanoma cells. The anti-oxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); nitric oxide; singlet oxygen; hydroxyl radical scavenging; and xanthine oxidase. The inhibitory activities against collagenase, elastase, hyaluronidase, and tyrosinase were employed for anti-aging. The anti-melanogenic was assessed in B16F10 melanoma cells by melanin synthesis and intracellular tyrosinase inhibitory activity. The volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS). The EO was a complex mixture mainly consisting of monoterpenes and sesquiterpenes. The results revealed that tairin and shima EOs showed strong anti-oxidant activities against DPPH and nitric oxide, hydroxyl radical scavenging activity, and xanthine oxidase inhibition. Compared to shima EO; tairin EO exhibited strong anti-aging activity by inhibiting collagenase, tyrosinase, hyaluronidase, and elastase (IC50 = 11 ± 0.1; 25 ± 1.2; 83 ± 1.6; and 213 ± 2 μg/mL, respectively). Both EOs inhibited intracellular tyrosinase activity; thus, reducing melanin synthesis. These results suggest that tairin EO has better anti-oxidant/anti-aging activity than shima EO, but both are equally anti-melanogenic.

  13. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    Directory of Open Access Journals (Sweden)

    Herrera-Esparza R

    2015-08-01

    Full Text Available Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL with or without congenital heart block (CHB. The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage. Clinical and experimental data demonstrated that anti-Ro and anti-La autoantibodies functionally inhibit L-type calcium channels and induce abnormalities in electrical conduction of the cardiac myocytes. It has been 38 years since the first clinical description of CHB. Presently, the pathophysiology of CHB has been clarified through clinical and basic research studies.

  14. The Puzzle of Simultaneous Anti-Dumping and Anti-Subsidy Measures

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Hansen, Jørgen Drud

    Quite frequently an anti-subsidy investigation in the EU is paired with an anti-dumping investigation against the same non-EU producers. The final outcome may be a two-component duty where one duty addresses the ‘unfairness’ of the subsidy and the other the dumping behavior. The procedure may...... be a surprise, as the same total level of protection may be obtained by using the anti-dumping procedure exclusively. When calculating the two duties in the EU the outcome depends on whether the subsidies are export subsidies or domestic subsidies and this may also cause surprise. This paper addresses......’ competition completely and because a parallel investigation may increase the probability of a successful outcome for the petitioners. In contrast, we find that the different assumptions about the effect of export subsidies and domestic production subsidies on the dumping margin in the EU dual anti...

  15. Belgian recommendations on ANA, anti-dsDNA and anti-ENA antibody testing.

    Science.gov (United States)

    Van Blerk, M; Bossuyt, X; Humbel, R; Mewis, A; Servais, G; Tomasi, J P; Van Campenhout, C; Van Hoovels, L; Vercammen, M; Damoiseaux, J; Coucke, W; Van de Walle, P

    2014-04-01

    Autoantibodies to nuclear antigens, i.e. antinuclear antibodies (ANA), antibodies to double-stranded DNA (dsDNA) and extractable nuclear antigens (ENA), are useful as diagnostic markers for a variety of autoimmune diseases. In March 2010, the Belgian national External Quality Assessment Scheme sent a questionnaire on ANA, anti-dsDNA and anti-ENA antibody testing designed by the Dutch EASI (European Autoimmunity Standardization Initiative) team, to all clinical laboratories performing ANA testing. Virtually all laboratories completed the questionnaire (97·7%, 127/130). This paper discusses the results of this questionnaire and provides valuable information on the state-of-the-art of ANA, anti-dsDNA and anti-ENA antibody testing as practiced in the Belgian laboratories. In addition, this work presents practical recommendations developed by the members of the advisory board of the scheme as a result of the outcome of this study.

  16. Anti-p200 pemphigoid (anti-laminin-γ1 pemphigoid demonstrating pathergy

    Directory of Open Access Journals (Sweden)

    Morgan McCarty, DO

    2015-12-01

    Full Text Available Anti-p200 pemphigoid, also called anti-laminin-γ1 pemphigoid, is a recently defined entity. First reported in 1996, the incidence is relatively rare, with approximately 70 reports in the literature. Clinical presentation is heterogeneous, but the disease most commonly mimics bullous pemphigoid with urticarial papules, plaques, or tense bullae on the trunk or extremities. Described here is a case with additional features of pathergy that have not yet been reported in the literature.

  17. Anti-aging and anti-microbial effects of melleolide on various types of yeast.

    Science.gov (United States)

    Nakaya, Shigeru; Kobori, Hajime; Sekiya, Atsushi; Kawagishi, Hirokazu; Ushimaru, Takashi

    2014-01-01

    The chronological lifespan (CLS) of the budding yeast Saccharomyces cerevisiae is a model for the aging of post-mitotic cells in higher eukaryotes. In this study, we found that the sesquiterpene aryl ester melleolide expands the CLS of budding yeast. In contrast, melleolide compromised the CLS of the fission yeast Schizosaccharomyces pombe. This indicates that melleolide might have a potential anti-aging activity against some types of cell, and that it might be useful as a selective anti-fungal drug.

  18. Hemolytic disease of the newborn due to isoimmunization with anti-E antibodies: a case report.

    Science.gov (United States)

    Sarici, S Umit; Alpay, Faruk; Yeşilkaya, Ediz; Ozcan, Okan; Gökçay, Erdal

    2002-01-01

    Minor blood group hemolytic disease is extremely rare, since the overall potency of minor blood groups in inducing antibodies is significantly lower when compared with that of Rh (D) antigen. We hereby report a very rare case of severe neonatal anti-E hemolytic disease due to E minor blood group incompatibility. A term newborn born to a 27-year-old, gravida 3, para 3 mother was referred due to a high and increasing serum bilirubin level despite phototherapy on the 4th day of life. On admission physical examination was normal except for the jaundice, and results of the laboratory investigation demonstrated a moderate-to-severe anemia (hemoglobin 7.8 g/dl) and a severe hemolytic hyperbilirubinemia (serum total and indirect bilirubin levels 36 mg/ dl and 32.8 mg/dl, respectively; reticulocyte count 15%; and a positive direct antiglobulin test). As there was no apparent cause of the hemolytic disease such as Rh or ABO incompatibilities, further investigation (a positive indirect antiglobulin test and a positive irregular anti-E antibody in both the patient and mother, and minor blood group antigen profiles in family members compatible with E minor blood group isoimmunization) revealed the presence of anti-E hemolytic disease due to E minor blood group incompatibility. Two exchange transfusions with a 12-hour-interval were performed with minor blood group compatible fresh whole blood, and the patient was discharged in a healthy condition on the 10th postnatal day. If the most common causes of severe neonatal hemolytic disease such as Rh and ABO incompatibilities cannot be demonstrated in a newborn with significant hemolytic hyperbilirubinemia, anti-E hemolytic disease should strongly be considered in differential diagnosis. It should be kept in mind that a very severe from of minor group antibody hemolytic disease characterized by anemia and severe hyperbilirubinemia many exchange transfusions may be encountered during the course of the disease.

  19. IN VIVO ANTI INFLAMMATORY AND ANTI ARTHRITIC ACTIVITY OF ETHANOLIC EXTRACT OF ASPARAGUS RACEMOSUS ROOTS

    Directory of Open Access Journals (Sweden)

    Suchita Mittal

    2013-04-01

    Full Text Available The present study is aimed to appraise the anti-inflammatory and anti-arthritic activity of ethanolic extract of Asparagus racemosus roots belonging to family Liliaceae. Carrageenan is used to induce inflammation and Freund’s Complete Adjuvant is used to induce arthritis. The result of this study revealed that Asparagus racemosus show potent effect on both the condition at a dose of 200mg/kg and 400mg/kg respectively.

  20. Anti-EU and Anti-LGBT Attitudes in Poland: Considering Quantitative and Qualitative Evidence

    Directory of Open Access Journals (Sweden)

    Chojnicka Joanna

    2015-10-01

    Full Text Available The purpose of this study is to investigate anti-EU and anti- LGBT attitudes in Poland on the basis of quantitative evidence (statistical data and qualitative evidence (discourse analysis of statements expressed on the Internet. As Euroscepticism seems to frequently appear in conjunction with prejudice against LGBT (lesbian, gay, bisexual and transsexual or transgender persons, the task of this article is to find out whether they may have a common foundation and what it may be.

  1. Licorice: a possible anti-inflammatory and anti-ulcer drug.

    Science.gov (United States)

    Aly, Adel M; Al-Alousi, Laith; Salem, Hatem A

    2005-09-20

    The purpose of this investigation was to study the anti-inflammatory activities of both glycerrhitinic acid (GA) and the aqueous licorice extract (ALE) in comparison with diclofenac sodium (DS) (10 mg/kg), using the carrageenan-induced paw edema model in male albino rats. In addition, the anti-ulcer activities of ALE, famotidine (FT), and a combination of ALE and FT using indomethacin-induced ulceration technique in rat stomach were investigated. Conventional DS tablets containing GA, as well as DS chewable tablets containing either GA or ALE with different tastes were prepared. Also, rapidly disintegrating FT tablets were prepared using direct compression and camphor sublimation methods. ALE or GA produced significant anti-inflammatory activity similar to DS, and when taken concomitantly, there is no possible antagonism. The anti-ulcer activity of licorice was found to be similar to that of FT in indomethacin-induced ulceration technique in rat stomach. Combination therapy of both FT and licorice showed higher anti-ulcer activity than either of them alone. Generally, tablets containing the crosslinked sodium carboxymethyl cellulose (AcDisol) showed more rapidly disintegrating effect than those including Sodium starch glycolate (Primojel). The oral disintegration was very rapid for all the tested formulations. Also, the amount of FT absorbed from the oral cavity was nearly 9 from 10 mg theoretically present in each formula. It could be concluded that both GA and ALE have anti-inflammatory activity comparable with DS. It may be recommended to add ALE to either FT or diclofinac for more effective anti-inflammatory or anti-ulcer formulations, respectively.

  2. Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

    OpenAIRE

    XU, DUNQUAN; Li, Yan; Zhang, Bo; Wang, Yanxia; Liu, Yi; Luo, Ying; Niu, Wen; Dong, Mingqing; Liu, Manling; Dong, Haiying; Zhao, Pengtao; Li, Zhichao

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The pres...

  3. The Modern Anti-Semitism Israel Model: An empirical relationship between modern anti-Semitism and opposition to Israel

    Directory of Open Access Journals (Sweden)

    Florette Cohen

    2011-04-01

    Full Text Available The current paper reviews our program of research that has examined some of the causes and consequences of anti-Semitism in which a new theoretical model of anti-Semitism is presented and tested in six experiments. The model proposes that mortality salience increases anti-Semitism and that anti-Semitism often manifests as hostility towards Israel. In accord with predictions, results show that existential fears lead to higher anti-Semitism and reduced support for Israel. Collectively, these results may serve as a preliminary contribution to explaining the continuation of anti-Semitism.

  4. Sterols from Mytilidae show anti-aging and neuroprotective effects via anti-oxidative activity.

    Science.gov (United States)

    Sun, Yujuan; Lin, Yanfei; Cao, Xueli; Xiang, Lan; Qi, Jianhua

    2014-11-25

    For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.

  5. Anti-anginal and anti-ischemic effects of late sodium current inhibition.

    Science.gov (United States)

    Wimmer, Neil J; Stone, Peter H

    2013-02-01

    The effective treatment of coronary artery disease targets two distinct goals, controlling symptomatic angina and decreasing the adverse events associated with ischemia. Traditional anti-anginal and anti-ischemic drugs function by altering the determinants of myocardial oxygen supply or demand, usually by altering loading conditions, changing the heart rate, or impacting contractility. Blockade of the late inward sodium current, late I(Na), offers another target for the treatment of ischemia. Blockade of late I(Na) reduces the sodium and calcium overload that follows ischemia. This improves myocardial relaxation and reduces left ventricular diastolic stiffness, in turn enhancing myocardial contractility and perfusion. Ranolazine, a late I(Na) inhibitor, has been shown to provide both anti-anginal and anti-ischemic benefits without significant alterations in the heart rate and blood pressure in patients with stable coronary artery disease. When evaluated in patients with acute coronary syndrome, ranolazine has been shown to decrease recurrent ischemia, but not significantly reduce the risk of death or myocardial infarction. This review will address the rationale that inhibition of the late sodium current is beneficial in reducing cardiac dysfunction during ischemia, and discuss the clinical studies supporting the use of ranolazine for its anti-anginal and anti-ischemic effects.

  6. The anti-melanogenic effect of pycnogenol by its anti-oxidative actions.

    Science.gov (United States)

    Kim, You Jung; Kang, Ki Sung; Yokozawa, Takako

    2008-07-01

    Pycnogenol is a natural plant extract from pine bark that contains compounds that have anti-oxidative, free-radical scavenging properties. In this work, utilizing cultured B16 melanoma cells (B16 cells), pycnogenol was investigated for its ability to inhibit tyrosinase activity and melanin biosynthesis. We also examined the anti-oxidative power of pycnogenol by measuring its suppressive effect against peroxynitrite (ONOO-), superoxide (.O2), nitric oxide (NO.), and hydroxyl radical (.OH)-scavenging activities using an electron spin resonance spectrometer. Results show that pycnogenol had a strong anti-tyrosinase activity and suppressed melanin biosynthesis. Further, our results showed that through its anti-oxidative properties, pycnogenol suppressed .O2) NO., ONOO-, and .OH in in vitro assays, and reactive species, ONOO-, .O2, and NO., while up-regulating the reduced glutathione/oxidized glutathione ratio in B16 cells. Based on the findings, we propose that pycnogenol exerts anti-melanogenic activity via its anti-oxidative actions.

  7. Analgesic, anti-inflammatory and anti-arthritic activity of Cassia uniflora Mill

    Institute of Scientific and Technical Information of China (English)

    She S Chaudhari; Sanjay R Chaudhari; Machindra J Chavan

    2012-01-01

    Objective: To evaluate the analgesic, anti-inflammatory and anti-arthritic activity of leaves of Cassia uniflora (C. uniflora) Mill. Methods: Petroleum ether, ethyl acetate and methanolic extract of C. uniflora (100 and 200 mg/kg, body weight) was screened for analgesic (Eddy's hot plate and acetic acid induced writhing), anti-inflammatory (Carrageenan induced paw edema) and anti-arthritic (Complete Freund's Adjuvant induced arthritis). In Complete Freund's Adjuvant arthritis model degree of inflammation was evaluated by hind paw swelling, body weight, and biochemical parameters and supported by radiological analysis. Results: Treatment with extracts of C. uniflora showed significant (P<0.05) and dose dependant increase in paw licking time in Eddy's hot plate method. In writhing test, extracts were significantly reduced the number of writhes. A dose dependant and significant inhibition of edema was observed in carrageenan induced paw edema. Petroleum ether extract at a dose of 100 mg/kg body weight showed most potent and significant activity which is supported by the results of body weight, biochemical parameters and radiological analysis in complete Freund's Adjuvant arthritis model. Conclusion:The extract possesses analgesic, anti-inflammatory and anti-arthritic activity which may be mediated through the phytochemical constituents of the plant.

  8. Anti-tumor and anti-viral activities of Galanthus nivalis agglutinin (GNA)-related lectins.

    Science.gov (United States)

    Wu, Lei; Bao, Jin-Ku

    2013-04-01

    Galanthus nivalis agglutinin (GNA)-related lectin family, a superfamily of strictly mannose-binding specific lectins widespread among monocotyledonous plants, is well-known to possess a broad range of biological functions such as anti-tumor, anti-viral and anti-fungal activities. Herein, we mainly focused on exploring the precise molecular mechanisms by which GNA-related lectins induce cancer cell apoptotic and autophagic death targeting mitochondria-mediated ROS-p38-p53 apoptotic or autophagic pathway, Ras-Raf and PI3K-Akt anti-apoptotic or anti-autophagic pathways. In addition, we further discussed the molecular mechanisms of GNA-related lectins exerting anti-viral activities by blocking the entry of the virus into its target cells, preventing transmission of the virus as well as forcing virus to delete glycan in its envelope protein and triggering neutralizing antibody. In conclusion, these findings may provide a new perspective of GNA-related lectins as potential drugs for cancer and virus therapeutics in the future.

  9. Anti-Tumor Effect and Anti-Inflammatory Activity of Boschniakia rossica

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the anti-tumor effect and anti-inflammatory activity of Boschniakia rossica (BR). Methods: The expression of tumor marker, GST-P, p53 and p21ras proteins in promotion stage of rat chemical hepatocarcinogenesis were examined by immunohistochemical technique ABC method. Anti-tumor effect of BR was investigated by inhibitory test on Sarcoma180. Anti-inflammatory activity of BR was tested by xylene-induced mouse ear swelling method. Results: BR-H2O extract (the H2O extract fractionated from BR-Methanol extract with CH2Cl2 and H2O) 500 mg/kg has inhibitory effect on the formation of diethylnitrosamine (DEN)-induced glutathione S-transferase placental form (GST-P) positive foci in rat liver with the expression of mutant p53 and p21ras proteins lower than those of non-treated hepatic preneoplastic lesions. BR extract showed inhibitory effect on Sarcoma180 and anti-inflammatory effect in mice by xylene-induced mouse ear swelling tests. Conclusion: BR- H2O extract exerted inhibitory effect on DEN-induced preneoplastic hepatic foci in promotion stage of rat chemical hepatocarcinogenesis and might suppress the growth of solid Sarcoma180 in mice. Both CH2Cl2 and H2O extract from BR exerted anti-inflammatory effect in mice.

  10. Radioimmunotherapy using {sup 131}I-rituximab in patients with advanced stage B-cell non-Hodgkin's lymphoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, Maren; Reisinger, Ingrid; Humplik, Beatrice I.; Reim, Christel; Kroessin, Thomas; Avril, Norbert; Munz, Dieter L. [Charite - Universitaetsmedizin Berlin, Clinic for Nuclear Medicine, Berlin (Germany); Srock, Stefanie; Pezzutto, Antonio [Charite - Universitaetsmedizin Berlin, Department of Haematology and Oncology, Berlin (Germany)

    2005-10-01

    The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using {sup 131}I-rituximab in previously heavily treated patients with B-cell non-Hodgkin's lymphoma (B-NHL). Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2-7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with {sup 131}I using the Iodogen method. The administered activity (2,200{+-}600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical. No acute adverse effects were observed after the administration of{sup 131}I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8{+-}2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months' follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes. (orig.)

  11. IGFBP-4 Anti-Angiogenic and Anti-Tumorigenic Effects Are Associated with Anti-Cathepsin B Activity

    Directory of Open Access Journals (Sweden)

    María J Moreno

    2013-05-01

    Full Text Available Insulin-like growth factor-binding protein 4 (IGFBP-4/IBP-4 has potent IGF-independent anti-angiogenic and antitumorigenic effects. In this study, we demonstrated that these activities are located in the IGFBP-4 C-terminal protein fragment (CIBP-4, a region containing a thyroglobulin type 1 (Tg1 domain. Proteins bearing Tg1 domains have been shown to inhibit cathepsins, lysosomal enzymes involved in basement membrane degradation and implicated in tumor invasion and angiogenesis. In our studies, CIBP-4 was shown to internalize and co-localize with lysosomal-like structures in both endothelial cells (ECs and glioblastoma U87MG cells. CIBP-4 also inhibited both growth factor-induced EC tubulogenesis in Matrigel and the concomitant increases in intracellular cathepsin B (CatB activity. In vitro assays confirmed CIBP-4 capacity to block recombinant CatB activity. Biodistribution analysis of intravenously injected CIBP-4-Cy5.5 in a glioblastoma tumor xenograft model indicated targeted accumulation of CIBP-4 in tumors. Most importantly, CIBP-4 reduced tumor growth in this animal model by 60%. Pleiotropic anti-angiogenic and anti-tumorigenic activities of CIBP-4 most likely underlie its observed therapeutic potential against glioblastoma.

  12. Biological Characterization of Cynara cardunculus L. Methanolic Extracts: Antioxidant, Anti-proliferative, Anti-migratory and Anti-angiogenic Activities

    Directory of Open Access Journals (Sweden)

    Maria Duarte

    2012-12-01

    Full Text Available Cynara cardunculus (Cc is a multipurpose species; beyond its use in southwestern European cuisine, it is also used for the production of solid biofuel, seed oil, biodiesel, paper pulp and cheese, as well as animal feed. In addition, Cc has a long tradition of use in folk medicine as a diuretic and liver protector. The value of this species as a source of bioactive compounds is known; however, pharmacological use would further increase its cultivation. The main goal of the current work was to evaluate the potential of Cc as source of anti-carcinogenic phytochemicals. Different methanolic extracts obtained from wild and cultivated plants were tested for antioxidant activity and effect on breast tumor cell viability. The most effective extract, both as antioxidant and inhibition of tumor cell viability, was tested for effects on angiogenesis and tumor cell migration capacity. All the extracts tested had high antioxidant activity; however, only green leaves and dry head extracts exhibit anti-proliferative activity. Green cultivated leaves (GCL were the most effective extract both as antioxidant and inhibiting the proliferation of tumor cells; it is equally active inhibiting tumor cell migration and in vivo angiogenesis. GCL extract is an effective inhibitor of several key points in tumor development and thus a promising source of anti-carcinogenic phytochemicals.

  13. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

    Full Text Available Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin lectin, concanavalin A, Galanthus nivalis (snowdrop agglutinin-related lectins, Musa acuminata (banana lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  14. Can HB vaccine yield a booster effect on individuals with positive serum anti-HBs and anti-HBc markers?

    Institute of Scientific and Technical Information of China (English)

    Ru-Xiang Wang; Christina Y. Shi; Ying Guo; Chang-Hong Yang; Yu Song; Juan Chen; Fu-Sheng Pang; Shao-Ping Lei; Xiao-Ming Jia; Jin-Ying Wen

    2004-01-01

    AIM: To evaluate if HB vaccination can yield a booster effecton the anti-HBs level of those naturally acquired HBV positivemarkers.METHODS: Sera were collected from 1399 newly enrolleduniversity students aged between 18-20 years at theentrance medical examination in 2001. Forty-four students(28 males and 16 females) with positive serum anti-HBs and anti-HBc markers served as an observation group and another 44 students (24 males and 20 females) without any HBV markers as the control. HB vaccination was given to all the students without positive serum HBs Ag according to 0,1, 6 month regimen and the peripheral venous blood was sampled from those of both observation and control groups for anti-HBs detection one month after the second and third doses. Anti-HBs levels were measured by ELISA.RESULTS: The seroconversion rate of anti-HBs in the control group was 100% after the second dose, but the geometric mean titers (GMTs) were low. The tendency of serum anti-HBs changes after the 3rd dose was completely different between the two groups. Although more than half of those with positive anti-HBs and anti-HBc showed a mild increase of anti-HBs levels after the 2nd boosting dose (mean anti-HBs level was 320:198 mIU), but the increase of serum anti-HBs titer was much smaller than that in the control group. The averages of their initial serum anti-HBs levelsand the levels after the 2nd and 3rd doses were 198, 320 and 275 mIU respectively. All the subjects from the control group had an obvious increase in their serum anti-HBs levels which was nearly 4 times the baseline level (302:78 mIU).CONCLUSION: HB vaccination can not enhance anti-HBs levels in those with positive serum anti-HBs and anti-HBc markers.

  15. Anti-synchronization Between Coupled Networks with Two Active Forms*

    Institute of Scientific and Technical Information of China (English)

    WU Yong-Qing; SUN Wei-Gang; LI Shan-Shan

    2011-01-01

    This paper studies anti-synchronization and its control between two coupled networks with nonlinear signal's connection and the inter-network actions. If anti-synchronization does not exist between two such networks, adaptive controllers are designed to anti-synchronize them. Different node dynamics and nonidentical topological structures are considered and useful criteria for anti-synchronization between two networks are given. Numerical examples are presented to show the efficiency of our derived results.

  16. Anti-C1q antibodies in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Orbai, A-M; Truedsson, L; Sturfelt, G

    2015-01-01

    OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

  17. Anti-microbial antibodies in celiac disease: Trick or treat?

    Institute of Scientific and Technical Information of China (English)

    Maria Papp; Ildiko Foldi; Istvan Altorjay; Eszter Palyu; Miklos Udvardy; Judit Tumpek; Sandor Sipka; Ilma Rita Korponay-Szabo; Eva Nemes; Gabor Veres; Tamas Dinya; Attila Tordai; Hajnalka Andrikovics; Gary L Norman; Peter Laszlo Lakatos

    2009-01-01

    AIM: To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti- OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients. METHODS: 190 consecutive CD patients [M/F: 71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti- Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD).RESULTS: 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, antimicrobial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+: 3.13; 95% CI: 2.08-4.73)was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis ( P = 0.019).CONCLUSION: The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation.Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.

  18. Anti-NMDA Receptor Encephalitis in a Pregnant Woman

    OpenAIRE

    Kim, JiYoung; Park, Seung Ha; Jung, Yu Ri; Park, Soon Won; Jung, Dae Soo

    2015-01-01

    Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti-NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor ence...

  19. Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities

    Directory of Open Access Journals (Sweden)

    Surached Thitimuta

    2017-03-01

    Full Text Available The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE (Camellia sinensis L.. The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl4-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE’s principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl4-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl4 intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins.

  20. Study ofe+e- to Lambda anti-Lambda, Lambda anti-Sigma^0,Sigma^0 anti-Sigma^0 using Initial State Radiation with BaBar

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2007-09-14

    We study the e+e- --> Lambda anti-Lambda gamma, Lambda anti-Sigma0 gamma, Sigma0 anti-Sigma0 gamma processes using 230 fb-1 of integrated luminosity collected by the BaBar detector at e+e- center-of-mass energy of 10.58 GeV. From the analysis of the baryon-antibaryon mass spectra the cross sections for e+e- --> Lambda anti-Lambda, Lambda anti-Sigma0, Sigma0 anti-Sigma0 are measured in the dibaryon mass range from threshold up to 3 GeV/c{sup 2}. The ratio of electric and magnetic form factors, |G{sub E}/G{sub M}|, is measured for e+e- --> Lambda anti-Lambda, and limits on the relative phase between Lambda form factors are obtained. We also measure the J/psi --> Lambda anti-Lambda, Sigma0 anti-Sigma0 and psi(2S) --> Lambda anti-Lambda branching fractions.

  1. Precision spectroscopy with reactor anti-neutrinos

    CERN Document Server

    Huber, P; Huber, Patrick; Schwetz, Thomas

    2004-01-01

    In this work we present an accurate parameterization of the anti-neutrino flux produced by the isotopes 235U, 239Pu and 241Pu in nuclear reactors. We determine the coefficients of this parameterization, as well as their covariance matrix, by performing a fit to spectra inferred from experimentally measured beta spectra. Subsequently we show that flux shape uncertainties play only a minor role in the KamLAND experiment, however, we find that future reactor neutrino experiments to measure the mixing angle $\\theta_{13}$ are sensitive to the fine details of the reactor neutrino spectra. Finally, we investigate the possibility to determine the isotopic composition in nuclear reactors through an anti-neutrino measurement. We find that with a 3 month exposure of a one ton detector the isotope fractions and the thermal reactor power can be determined at a few percent accuracy, which may open the possibility of an application for safeguard or non-proliferation objectives.

  2. [Anti-aging medicine: science or marketing ?].

    Science.gov (United States)

    Cogan, E

    2015-09-01

    Anti-aging medicine is self defined as a preventive medicine, combining nutritional recommendations, dietary supplements, prescriptions for hormones and various aesthetic techniques. The essential aim is to reduce the risk of aging, both psychically, physically and aesthetically. Although many scientific studies in animals or in vitro models have demonstrated the deleterious role of oxidative stress and of hormonal, vitamin or trace elements deficiencies, the transposition to humans of these findings is marginal and does not justify the therapeutic proposals advocated by the anti aging medicine. These practices are mostly not based on any scientific basis both in the diagnostic and therapeutic fields. These approaches are particularly costly for gullible patients in search of well being and abused by a carefully organized marketing involving tacit complicity of doctors, laboratories and firms producing hormones and dietary supplements and various substances devoted for aesthetic purposes.

  3. Trends in Anti-Epileptic Drug Development

    Directory of Open Access Journals (Sweden)

    Lennart Gram

    1990-01-01

    Full Text Available Several avenues are being explored in the development of new anti-epileptic drugs (AEDs. For a number of years efforts have been directed towards compounds which may augment neuronal inhibition, and these efforts have resulted in the development of several valuable drugs. More recently, increased attention has been focused on the role which excitatory transmitters may play in epileptogenesis, and various substances which decrease excitation are currently being investigated at the preclinical level. Since considerable potential still resides in several of the drugs already on the market, resources have been spent on trying to modify/improve the chemical formula of some of these substances, and a number of new drugs has emerged as a result of this approach. The major accomplishments reviewed here in the development of new anti-epileptic drugs suggest that even more successful advances may be achieved in the near future.

  4. Medicinal plants with anti-inflammatory activities.

    Science.gov (United States)

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

  5. Anti-inflammatory actions of acupuncture

    Directory of Open Access Journals (Sweden)

    Freek J. Zijlstra

    2003-01-01

    Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

  6. Prospects for Anti-Biofilm Pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Philip S. Stewart

    2015-08-01

    Full Text Available This commentary highlights several avenues currently being pursued in research labs to the development of new anti-biofilm pharmaceuticals. There is a real need for alternative therapeutic modalities for treating the persistent infections that sometimes form on implanted medical devices or compromised niches within the body. Strategies being researched include discovering new antimicrobial agents that kill microorganisms in biofilms more effectively than do existing antibiotics, designing drugs that block microbial adhesion or interfere with intercellular communication, developing chemistries to disperse biofilms, and combining agents with different mechanisms of action. Though the need is great, the pathway to commercialization of new drugs is steep. One possible streamlined approach to navigating the regulatory approval process is to repurpose old drugs, a strategy that a few groups have shown can yield agents with anti-biofilm properties.

  7. Ketogenic diet exhibits anti-inflammatory properties.

    Science.gov (United States)

    Dupuis, Nina; Curatolo, Niccolo; Benoist, Jean-François; Auvin, Stéphane

    2015-07-01

    The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation-induced epileptic encephalopathies. In a lipopolysaccharide (LPS)-induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long-chain n-3 polyunsaturated fatty acids (PUFAs), suggesting that the anti-inflammatory effect of KD was probably not due to an increase in anti-inflammatory n-3 PUFA derivatives. These properties might be of interest in some conditions such as fever-induced refractory epileptic encephalopathy in school-aged children.

  8. The bizarre anti-de Sitter spacetime

    Science.gov (United States)

    Sokołowski, Leszek M.

    2016-08-01

    Anti-de Sitter spacetime is important in general relativity and modern field theory. We review its geometrical features and properties of light signals and free particles moving in it. By applying only the elementary tools of tensor calculus, we derive ab initio of all these properties and show that they are really weird. One finds superluminal velocities of light and particles, infinite particle energy necessary to escape at infinite distance and spacetime regions inaccessible by a free fall, though reachable by an accelerated spaceship. Radial timelike geodesics are identical to the circular ones and actually all timelike geodesics are identical to one circle in a fictitious five-dimensional space. Employing the latter space, one is able to explain these bizarre features of anti-de Sitter spacetime; in this sense the spacetime is not self-contained. This is not a physical world.

  9. Anti-aging pharmacology: Promises and pitfalls.

    Science.gov (United States)

    Vaiserman, Alexander M; Lushchak, Oleh V; Koliada, Alexander K

    2016-11-01

    Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness. A number of pharmacological agents targeting basic aging pathways (i.e., calorie restriction mimetics, autophagy inducers, senolytics etc.) are now under investigation. This review summarizes the literature related to advances, perspectives and challenges in the field of anti-aging pharmacology.

  10. The bizarre anti-de Sitter spacetime

    CERN Document Server

    Sokolowski, Leszek M

    2016-01-01

    Anti--de Sitter spacetime is important in general relativity and modern field theory. We review its geometrical features and properties of light signals and free particles moving in it. Applying only elementary tools of tensor calculus we derive \\textit{ab initio\\/} all these properties and show that they are really weird. One finds superluminal velocities of light and particles, infinite particle energy necessary to escape at infinite distance and spacetime regions inaccessible by a free fall, though reachable by an accelerated spaceship. Radial timelike geodesics are identical to the circular ones and actually all timelike geodesics are identical to one circle in a fictitious five--dimensional space. Employing the latter space one is able to explain these bizarre features of anti--de Sitter spacetime; in this sense the spacetime is not self--contained. This is not a physical world.

  11. Anti-GBM Disease in Pregnancy

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeet Adnan MD

    2015-12-01

    Full Text Available Antiglomerular basement membrane (GBM disease presenting during pregnancy is uncommon. We present a case of a pregnant female who presented with acute renal failure requiring dialysis due to anti-GBM disease. She responded well to plasma exchange, high-dose steroids, and hemodialysis. Cyclophosphamide was discussed but not given at the patient’s request due to concerns for the well-being of the fetus. Unfortunately, she suffered a spontaneous abortion in her eighth week of pregnancy. Subsequently, she had progressive improvement in her renal function and became hemodialysis independent at 2 weeks after diagnosis. Her renal function returned to baseline 3 months after diagnosis. We present this case in detail and review the literature regarding anti-GBM disease in pregnancy.

  12. Asymptotically anti-de Sitter Proca Stars

    CERN Document Server

    Duarte, Miguel

    2016-01-01

    We show that complex, massive spin-1 fields minimally coupled to Einstein's gravity with a negative cosmological constant, admit asymptotically anti-de Sitter self-gravitating solutions. Focusing on 4-dimensional spacetimes, we start by obtaining analytical solutions in the test-field limit, where the Proca field equations can be solved in a fixed anti-de Sitter background, and then find fully non-linear solutions numerically. These solutions are a natural extension of the recently found asymptotically flat Proca stars and share similar properties with scalar boson stars. In particular, we show that they are stable against spherically symmetric linear perturbations for a range of fundamental frequencies limited by their point of maximum mass. We finish with an overview of the behavior of Proca stars in $5$ dimensions.

  13. 76 FR 76896 - International Anti-Fouling System Certificate

    Science.gov (United States)

    2011-12-09

    ... SECURITY Coast Guard 46 CFR Part 8 RIN 1625-AB79 International Anti-Fouling System Certificate AGENCY... regulations to add the International Anti-fouling System (IAFS) Certificate to the list of certificates a... Harmful Anti-fouling Systems on Ships, 2001. This final rule will enable recognized...

  14. 76 FR 54419 - International Anti-Fouling System Certificate

    Science.gov (United States)

    2011-09-01

    ... SECURITY Coast Guard 46 CFR Part 8 RIN 1625-AB79 International Anti-Fouling System Certificate AGENCY... vessel inspection regulations to add the International Anti-fouling System (IAFS) Certificate to the list... Convention on the Control of Harmful Anti-fouling Systems on Ships, 2001. This proposed rule would...

  15. 48 CFR 352.203-70 - Anti-lobbying.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Anti-lobbying. 352.203-70... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 352.203-70 Anti-lobbying. As prescribed in 303.808-70, the Contracting Officer shall insert the following clause: Anti-Lobbying...

  16. Striking the Right Balance : Effectiveness of Anti-Doping Policies

    NARCIS (Netherlands)

    de Hon, O.M.

    2016-01-01

    Doping, and anti-doping, is in the news on a continuous basis. At the core of these stories and discussions is the question how effective anti-doping policies are to curb the use of doping in sports. Anti-doping policies are based on ethical values, a juridical framework, laboratory analyses, educat

  17. Uncertainties in the Anti-neutrino Production at Nuclear Reactors

    OpenAIRE

    Djurcic, Z.(Argonne National Laboratory, Argonne, Illinois, 60439, U.S.A.); Detwiler, J. A.; Piepke, A.; Foster Jr., V. R.; Miller, L.; Gratta, G.

    2008-01-01

    Anti-neutrino emission rates from nuclear reactors are determined from thermal power measurements and fission rate calculations. The uncertainties in these quantities for commercial power plants and their impact on the calculated interaction rates in electron anti-neutrino detectors is examined. We discuss reactor-to-reactor correlations between the leading uncertainties and their relevance to reactor anti-neutrino experiments.

  18. 15 CFR 742.19 - Anti-terrorism: North Korea.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: North Korea. 742.19...-CCL BASED CONTROLS § 742.19 Anti-terrorism: North Korea. (a) License Requirements. (1) All items on... anti-terrorism reasons require a license for export or reexport to North Korea. This includes all...

  19. 15 CFR 742.9 - Anti-terrorism: Syria.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Syria. 742.9 Section... BASED CONTROLS § 742.9 Anti-terrorism: Syria. (a) License requirements. (1) If AT Column 1 of the... required for export and reexport to Syria for anti-terrorism purposes. (2) The Secretary of State...

  20. 15 CFR 742.10 - Anti-terrorism: Sudan.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Sudan. 742.10 Section...-CCL BASED CONTROLS § 742.10 Anti-terrorism: Sudan. (a) License requirements. (1) If AT column 1 or AT... ECCN, a license is required for export to Sudan for anti-terrorism purposes. 1 AT column 1 refers...

  1. 15 CFR 742.8 - Anti-terrorism: Iran.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Anti-terrorism: Iran. 742.8 Section... BASED CONTROLS § 742.8 Anti-terrorism: Iran. (a) License Requirements. (1) A license is required for anti-terrorism purposes to export or reexport to Iran any item for which AT column 1 or AT column 2...

  2. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    1998-01-01

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  3. ANTI - OBESITY DRUGS : PRESENT AND FUTURE

    Directory of Open Access Journals (Sweden)

    Momin M. A

    2015-09-01

    Full Text Available The ideal anti - obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built - in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti - obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK, peptide YY (PYY and glucagon - like peptide - 1 (GLP - 1, and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti - obesity drug. However, GLP - 1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body - weight - lowering effects in humans, will perhaps also pave the way for other anti - obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it se ems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical

  4. Potential Anti-cancer Activity of Furanodiene

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhen Ba; Yan-ping Zheng; Hui Zhang; Xiu-yan Sun; Dong-hai Lin

    2009-01-01

    Objective: To study the anti-tumor activities of furanodiene (C15H20O), a primary sesquiterpene compound isolated from the essential oil of the rhizome of Curcuma wenyujin YH Chen et C. Ling(Wen Ezhu), in vitro and in vivo.Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2,HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhu as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed.Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0 μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively.Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

  5. European Anti-dumping Law and China

    Directory of Open Access Journals (Sweden)

    Piet Eeckhout

    1997-04-01

    Full Text Available The paper examines recent developments in the European Union's anti-dumping policy, as it is applied towards China. It concentrates on recent court cases involving dumping from China and on the basic non-market economy issue. The author essentially argues that the European Union's policy does not take account sufficiently of China's development towards a market economy, and that there are various legal flaws in the way the policy is applied.

  6. ANTI-DEPRESSANT POTENTIAL OF GHIYA

    Directory of Open Access Journals (Sweden)

    Kaur Satbir

    2012-04-01

    Full Text Available Lagenaria siceraria (Cucurbitaceae, popularly known as bottle gourd, lauki or ghiya, is a climbing plant, which bears hard-shelled and bottle-shaped gourds as fruits. Ghiya forms an excellent diet for people having digestive problems being rich in vitamins, iron and minerals. Since, it contains low calories, bottle gourd is an awesome foodstuff for shedding extra calories. The fruit possesses diuretic, emetic, and refrigerant properties. The ghiya (lauki juice is helpful in constipation, premature graying hair, urinary disorders and insomnia. However, there are no reports in literature pertaining to CNS actions of Lagenaria siceraria fruit. In the light of above, the present study was undertaken to test the anti-depressant potential of Lagenaria siceraria juice (LSJ. Lagenaria siceraria juice was administered at various concentrations ranging from 4%-16% v/v orally to Swiss mice (30g, once daily for 15 successive days. The anti-depressant activity was measured using Forced Swim Test (FST and Tail Suspension Test (TST. The efficacy of Lagenaria siceraria was compared to standard anti-depressant drugs viz: fluoxetine (20mg/kg, p.o, imipramine (15mg/kg, p.o and phenelzine (20 mg/kg, p.o. Lagenaria siceraria significantly reduced the immobility time of mice in both FST and TST. Prazosin, Baclofen, Sulpiride and p-CPA significantly antagonized this reduction in immobility duration. Furthermore, Lagenaria siceraria juice inhibited the monoamine oxidase (MAO enzyme and reduced significantly malondialdehyde (MDA levels. These findings reveal the anti-depressant potential of ghiya.

  7. Anti inflammatory activity of moringa oliefera. Lam.

    Science.gov (United States)

    Rao, K N; Gopalakrishnan, V; Loganathan, V; Nathan, S S

    1999-01-01

    The aqueous and ethanolic (90%) extract of the leaves of M.Oliera Lam (Fam: Moringaceae) were studied for their anti inflammatory action in ale albino rats. Two extracts exhibited maximum action within two hours of challenge. The aqueous extract sowed significant (P<0.01) odema suppression similar to that of Ibuprofen at the first hour of carrageenan injection. The results confirms the folkers claim of the plant.

  8. Anti-Stigma Projekte in der Psychiatrie

    OpenAIRE

    2006-01-01

    Die Stigmatisierung psychiatrischer Patienten und die daraus entstehenden negativen Folgen für Früherkennung, Behandlung und Compliance sind ein großes Problem für die Betroffenen und für das gesamte psychiatrische Versorgungssystem. Die World Psychiatric Association hat deshalb weltweit Anti-Stigma Projekte ins Leben gerufen und auch andere Institutionen versuchen auf verschiedenste Weise, die Stigmatisierung und Diskriminierung psychisch Kranker zu bekämpfen. Ziel der vorliegenden Arbeit wa...

  9. Anti-Integrin Therapy for Multiple Sclerosis

    OpenAIRE

    Eiji Kawamoto; Susumu Nakahashi; Takayuki Okamoto; Hiroshi Imai; Motomu Shimaoka

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper pr...

  10. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

    Directory of Open Access Journals (Sweden)

    Rohit Kumar

    2016-01-01

    Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators.

  11. Anti-fogging and anti-frosting behaviors of layer-by-layer assembled cellulose derivative thin film

    Science.gov (United States)

    Shibraen, Mahmoud H. M. A.; Yagoub, Hajo; Zhang, Xuejian; Xu, Jian; Yang, Shuguang

    2016-05-01

    Two cellulose derivatives, quaternized cellulose (QC) and carboxymethyl cellulose (CMC), were layer-by-layer (LbL) assembled to prepare a thin film. QC was also LbL assembled with two synthetic polyelectrolytes, poly(acrylic acid) (PAA) and poly(styrene sulfonate) (PSS), separately. The anti-fogging and anti-frosting properties of the assembled films were studied. QC/CMC thin film exhibits anti-fogging and anti-frosting behaviors, whereas QC/PAA and QC/PSS films do not have capacity for anti-fogging and anti-frosting. The anti-fogging and anti-frosting properties of QC/CMC film are attributed to that water molecules can be quickly adsorbed into the matrix of the film. The water adsorption of QC/CMC film was illustrated by the optical thickness increment.

  12. Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

    Energy Technology Data Exchange (ETDEWEB)

    Ribiero, Ruy M [Los Alamos National Laboratory

    2009-01-01

    To investigate the impact of humoral immunity on SIV replication, 11 rhesus macaques (RMs) were inoculated with the neutralization-sensitive strain SIVsmmD215. Seven RMs were treated every three weeks, with 50 mglkg of an anti-CD20 antibody (Rituxan, gift from Genentech) starting from day -7 p.i., as follows: four RMs were treated for two months, and three were treated for five months. The remaining four RMs were used as controls. Three RMs were completely depleted of CD20 cells. Four RMs only partially depleted CD20 cells in the LNs and intestine. The efficacy of tissue CD20 depletion predicted the ablation of antibody production, with SIVsmm seroconversion being delayed in the animals with complete tissue CD20 depletion, and neutralizing antibody production being significantly delayed and at low levels in all CD20-depleted RMs. There was no significant difference in acute or chronic VLs between CD20-depleted RMs and control monkeys, with a tendency for lower set-point VLs in CD20-depleted RMs. At 6 weeks p.i., cellular immune responses were significantly stronger in CD20 depleted RMs than in controls. After two years p.i., there was no significant difference in survival between CD20-depleted and control RMs. We concluded that CD20 depletion plays no significant role in the control of SIV replication or disease progression in SIVsmmD215-infected RMs.

  13. Anti-Inflammatory Effect of Allium ursinum

    Directory of Open Access Journals (Sweden)

    Alina Elena PÂRVU

    2014-03-01

    Full Text Available The aim of the present study was to evaluate Allium ursinum leaves and flowers extract anti-inflammatory effect. Plant extract 1:1 (w:v was prepared from A. ursinum leaves by a modified Squibb repercolation method. The in vivo anti-inflammatory effects were evaluated on a rat turpentine oil-induced inflammation (i.m. 6 mL/kg BW. The animals were randomly assigned to nine groups (n=8: negative control, inflammation, A. ursinum flower extract (AUF, A. ursinum leaves extract (AUL, indomethacin (INDO (20 mg/kg BW, aminoguanidine (AG (50 mg/kg b.w./d i.p. as a selective NOS2 inhibitor, NG-nitro L-arginine methyl ester (NAME (5 mg/kg b.w./d i.p. as a nonselective NOS inhibitor, L-arginine (ARG (100 mg/kg b.w./d i.p., NO synthesis substrate, and Trolox (20 mg/kg b.w./d i.p as an antioxidant. At 24h from inflammation induction total oxidative status (TOS, oxidative stress index (OSI, nitric oxide (NOx and in vitro phagocytosis test were reduced and the total antioxidative reactivity (TAR was increased by the testes plant extracts. AUF had a better inhibitory effect than AUL. In conclusion, we provided evidence for the hypothesis that A. ursinum leaves and flowers extract exerts anti-inflammatory activity by inhibiting the phagocytosis through the reduction of the nitro-oxidative stress.

  14. Standardization of anti-DNA antibody assays.

    Science.gov (United States)

    Pisetsky, David S

    2013-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus and represent important biomarkers for clinical and research purposes. These antibodies are part of a family of antibodies to nucleosomes and bind to conserved sites widely present on DNA. While the value of anti-DNA as a biomarker is well established, the assay for these antibodies has involved a variety of DNA sources and systems to detect DNA-anti-DNA interactions. The influence of these variations on antibody detection has complicated assay standardization. As an antigen, DNA has unique features since it is a highly charged polymer that has structural heterogeneity. This heterogeneity can affect antigenicity which can vary on the basis of DNA origin, size, conformation and mobility. In addition, as a polymer, DNA can promote patterns of antibody binding based on monogamous or bivalent interaction which require an extended polynucleotide structure. Understanding the nature of DNA as an antigen can facilitate interpretation of serological tests and underpin efforts at better standardization.

  15. ICAO's anti-SARS airport activities.

    Science.gov (United States)

    Finkelstein, Silvio; Curdt-Christiansen, Claus M

    2003-11-01

    To prevent SARS from spreading through air travel and in order to rebuild the confidence of the traveling public in the safety of air travel, ICAO has set up an "Anti-SARS Airport Evaluation Project." The first phase of this project was to develop a set of protective measures for international airports in affected areas to adopt and implement and then to send out, on the request of Contracting States, a team of inspectors to evaluate and assess airports and issue a "statement of evaluation" that the airport inspected complies with the ICAO anti-SARS protective measures. In cooperation with the World Health Organization (WHO), the first part of phase 1 was completed in early June this year, and the second part of phase 1 followed soon after. By mid-July, five international airports in Southeast Asia had been inspected and found to be in full compliance with the ICAO anti-SARS protective measures. The success of this ICAO project is believed to have contributed significantly to the recovery of international air travel and related industries now taking place. Phase 2 of the project is now being developed. It is aimed at preventing a resurgence of SARS, but it also contains elements to make the methodology developed applicable to future outbreaks of any other communicable disease in which the mode of transmission could involve aviation and/or the need to prevent the spread of the disease by air travel.

  16. Anti- Sporothrix spp. activity of medicinal plants

    Directory of Open Access Journals (Sweden)

    Stefanie Bressan Waller

    Full Text Available ABSTRACT Cases of sporotrichosis in humans and animals without satisfactory clinical response have increased, a warning sign of strains resistant to conventional antifungal agents. The urgent search for alternative therapies was an incentive for research on medicinal plants with anti-Sporothrix spp. properties. A bibliographic survey was performed based on scientific papers about in vitro and in vivo antifungal activity of essential oils and extracts of plants in differents solvents against the fungal of the Sporothrix schenckii complex. The study methodology consisted of a literature review in Google Scholar, Science Direct, Pubmed, Bireme and Springer link with papers from 1986 to 2015. We found 141 species of plants that were investigated, of which 100 species were concentrated in 39 botanical families that had confirmed anti-Sporothrix activity. Combretaceae, Asteraceae and Lamiaceae represented the botanical families with the greatest number of plants species with antifungal potential, using different methodologies. However, there are few studies with medicinal plants in experimental infection in animals that prove their activity in the treatment of sporotrichosis. It reinforces the need for further research related to standardization of in vitro methodologies and in vivo studies related to safety and to toxicity potential of these plants with anti-Sporothrix spp. activity.

  17. ANTI-ULCER ACTIVITY OF LEGUMINOSAE PLANTS

    Directory of Open Access Journals (Sweden)

    Noemi D. PAGUIGAN

    2014-03-01

    Full Text Available Context Ulcer is the most common gastrointestinal disturbance resulting from an inadequate gastric mucosal defense. Several drugs are available in the market to address the disease; however, these drugs are associated with unnecessary side effects. Objectives Previous research have confirmed the efficacy of plant extracts for possible treatment of the disease. This research aims to evaluate the anti-ulcer properties of medicinal plants. Methods Methanol extracts from the leaves of Intsia bijuga, Cynometra ramiflora, Tamarindus indica, Cassia javanica, Cassia fistula, Bauhini purpurea, Senna spectabilis, Senna siamea and Saraca thaipingensis were evaluated for their anti-ulcer activity using HCl-ethanol as ulcerogen. Results All extracts showed inhibitory activity with I. bijuga, T. indica, S. spectabilis and S. thaipingensis exhibiting more than 50% inhibition. S. thaipingensis showed the highest activity at 80%. S. spectabilis and S. thaipingensis were partitioned further into hexane, ethyl acetate and aqueous fractions. The aqueous and ethyl acetate fractions of S. spectabilis showed significant increased in its activity while the hexane and ethyl acetate fractions of S. thaipingensis gave higher activity than its aqueous portions. Conclusions We conclude that plant extracts are potential sources of new anti-ulcer agents.

  18. News exposure predicts anti-Muslim prejudice

    Science.gov (United States)

    Sibley, Chris G.; Osborne, Danny; Bulbulia, Joseph

    2017-01-01

    News coverage of Islamic extremism is reigniting debates about the media’s role in promoting prejudice toward Muslims. Psychological theories of media-induced prejudice date to the 1950’s, and find support from controlled experiments. However, national-scale studies of media effects on Muslim prejudice are lacking. Orthogonal research investigating media-induced prejudice toward immigrants has failed to establish any link. Moreover, it has been found that people interpret the news in ways that confirm pre-existing attitudes, suggesting that media induced Muslim prejudice in liberal democracies is unlikely. Here, we test the association between news exposure and anti-Muslim prejudice in a diverse national sample from one of the world’s most tolerant societies, where media effects are least likely to hold (N = 16,584, New Zealand). In support of media-induced Islamophobia, results show that greater news exposure is associated with both increased anger and reduced warmth toward Muslims. Additionally, the relationship between media exposure and anti-Muslim prejudice does not reliably vary with political ideology, supporting claims that it is widespread representations of Muslims in the news, rather than partisan media biases, that drives anti-Muslim prejudice. PMID:28362823

  19. Anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica

    Institute of Scientific and Technical Information of China (English)

    Mohan CG; Deepak M; Viswanatha GL; Savinay G; Hanumantharaju V; Rajendra CE; Praveen D Halemani

    2013-01-01

    Objective: To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. Methods: In vitro DPPH radical scavenging activity and lipoxygenase (LOX) inhibition assays were used to evaluate the anti-oxidant and anti-inflammatory activities respectively. Methanolic extract (MEMI), successive water extract (SWMI) and ethyl acetate fraction (EMEMI), n-butanol fraction (BMEMI) and water soluble fraction (WMEMI) of methanolic extract were evaluated along with respective reference standards. Results: In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC50 values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC50 value of 1.88 and found to be more potent compared to all the extracts and fractions. In in vitro LOX inhibition assay, the MEMI, EMEMI and BMEMI have showed significant inhibition of LOX enzyme activity with IC50 values of 96.71, 63.21 and 107.44 μg/mL respectively. While, reference drug Indomethacin also offered significant inhibition against LOX enzyme activity with IC50 of 57.75. Furthermore, MEMI was found to more potent than SWMI and among the fractions EMEMI was found to possess more potent antioxidant and anti-inflammatory activity. Conclusions: These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions.

  20. Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners.

    Science.gov (United States)

    Huang, Tien L; Vanden Eynde, Jean Jacques; Mayence, Annie; Donkor, Isaac O; Khan, Shabana I; Tekwani, Babu L

    2006-08-01

    A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3-6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4'-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 approximately 0.290 microM) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50 approximately 0.410 microM), which were 10- and 7-fold more potent than pentamidine (IC50 approximately 2.90 microM). Several of the more active anti-plasmodial agents (e.g. 2, 31, 33, 36-38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25-28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections.

  1. Partial overlap of anti-mycobacterial, and anti-Saccharomyces cerevisiae mannan antibodies in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Stefan Müller; Thomas Schaffer; Alain M Schoepfer; Annamarie Hilty; Thomas Bodmer; Frank Seibold

    2008-01-01

    AIM: To test whether humoral immune reaction against mycobacteria may play a role in anti-Saccharomyces cerevisiae antibodies (ASCA) generation in Crohn's disease (CD) and/or whether it correlates with clinical subtypes.METHODS: The dominant ASCA epitope was detected by Galanthus nivalis lectin (GNL)-binding assay. ASCA and IgG against mycobacterial lysates (M avium, M smegmatis, M chelonae, M bovis BCG, M avium ssp. paratuberculosis (MAP)] or purified lipoarabinomannans (LAM) were detected by ELISA. ASCA and anti-mycobacterial antibodies were affinity purified to assess cross-reactivities. Anti-mycobacterial IgG were induced by BCG-infection of mice.RESULTS: GNL bound to different extents to mycobacterial lysates, abundantly to purified mannose-capped (Man) I_AM from M tuberculosis, but not to uncapped LAM from M smegmatis. Fifteen to 45% of CD patients but only 0%-6% of controls were seropositive against different mycobacterial antigens. Anti-mycobacterial IgG correlated with ASCA (r=0.37-0.64; P=0.003-P<0.001). ASCA-positivity and deficiency for mannan-binding lectin synergistically associated with anti-mycobacterial IgG. In some patients, anti-mycobacterial antibodies represent cross-reactive ASCA. Vice-versa, the predominant fraction of ASCA did not cross-react with mycobacteria. Finally, fistulizing disease associated with antibodies against M avium, M smegmatis and MAP (P=0.024,0.004 and 0.045, respectively).CONCLUSION: Similar to ASCA, seroreactivity against mycobacteria may define CD patients with complicated disease and a predisposition for immune responses against ubiquitous antigens. While in some patients anti-mycobacterial antibodies strongly cross-react with yeast mannan; these cross-reactive antibodies only represent a minor fraction of total ASCA. Thus, mycobacterial infection unlikely plays a role in ASCA induction.

  2. Anti-Oxidative and Anti-Inflammatory Effects of Ginger in Health and Physical Activity: Review of Current Evidence

    OpenAIRE

    Nafiseh Shokri Mashhadi; Reza Ghiasvand; Gholamreza Askari; Mitra Hariri; Leila Darvishi; Mohammad Reza Mofid

    2013-01-01

    Background: Ginger (Zingiber officinale Rosc.) belongs to the family Zingiberaceae. The health-promoting perspective of ginger is attributed to its rich phytochemistry. This study aimed to review the current evidence on ginger effects as an anti-inflammatory and anti-oxidative. Methods: We searched MEDLINE for related publications using “ginger” and “anti-oxidative” and “ginger” and “anti-inflammatory” as keywords. This search had considered Papers that had been published between 2000 and 201...

  3. Solvability conditions for algebra inverse eigenvalue problem over set of anti-Hermitian generalized anti-Hamiltonian matrices

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-zhi; HAN Xu-li

    2005-01-01

    By using the characteristic properties of the anti-Hermitian generalized anti-Hamiltonian matrices, we prove some necessary and sufficient conditions of the solvability for algebra inverse eigenvalue problem of anti-Hermitian generalized anti-Hamiltonian matrices, and obtain a general expression of the solution to this problem. By using the properties of the orthogonal projection matrix, we also obtain the expression of the solution to optimal approximate problem of an n× n complex matrix under spectral restriction.

  4. 2658份血清标本中anti-HBs、anti-HBe、anti-HBc分布模式及形成机制的探讨%Distribution pattern and formation mechanism of anti-HBs, anti-HBe, anti-HBc in 2658 serum samples

    Institute of Scientific and Technical Information of China (English)

    孔丽清; 刘恩华; 齐雅君; 唱丽敏

    2013-01-01

    Objective:To explore the distribution pattern of antiboby markers during acute and chronic HBV infection and their formation mechanism.Methods:HBV infectious makers were quantified by chemiluminescent microparticle immunoassay (CMIA) in 2658 serum samples of outpatients and hospitalized patients,and the test data of antiboby markers were statistically grouped and analyzed.Results:The distribution rate of single antiHBsIgG was different from that of anti-HBsIgG+anti-HbcIgG,with statistical significance; the comparation of anti-H-BcIgG levels between HBsAg(N)+ anti-HBs(R) group and HBsAg(N)+ anti-HBs(R)+ anti-HBc(R) group had statistical significance (P<0.05; anti-HBe(S/CO) levels between HBsAg(R)+ anti-HBe(R)+ anti-HBc (R) group and HBsAg(R) +HBeAg(R)+ anti-HBc(R) group had statistical significance (P<0.01); anti-HBc(S/CO) levels between HBsAg(R)+ anti-HBe(R)+ anti-HBc(R) group and HBsAg(R) +HBeAg(N)+ anti-HBc(R) group had statistical significanc (P<0.05).Conclusion:Not only can HBV infectious markers be used for diagnosis of acute and chronic HBV infections,but also the stratification,cure-guide and evaluation.%目的:探讨HBV病毒急慢性感染过程中抗体类标志物的分布模式及形成机制.方法:采用化学发光微粒子免疫检测法(CMIA法)定量分析2012年2月10日-6月10日来我院就诊的2658例门诊或住院患者的血清标本中的HBV病毒感染标志物,根据抗原性标志物实验结果将抗体类标志物实验结果的分布模式分组进行统计学分析.结果:发现HBsAg无反应性组(N)内单纯anti-HbsIgG与有反应性分布差异有统计学意义;HBsAg有反应性组anti-HBeIgG+anti-HBcIgG有反应性分布与另两组组间比较差异有统计学意义(P<0.05);anti-HBsIgG、anti-HBcIgG、anti-HBeIgG表达含量在各实验组存在着差异.anti-HBcIgG含量在HBsAg(N)+ anti-HBs(R)组和HBsAg(N)+ anti-HBc(R)组差异有统计学意义(P<0.05);anti-HBe(S/CO)在HB-sAg(R)+ anti-HBe(R)+ anti

  5. Influence of sway motion on passive anti-rolling tank

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The passive anti-rolling tank is one of important ship stabilizers widely used today. But at present, research of the tank is most aimed at its rolling movement. In this paper, the influence of sway motion on the passive anti-rolling tank is considered, the mathematical model of "ship-passive anti-rolling tank" system coupled with sway motion is developed basing on the U-shaped passive anti-rolling tank theory. Both simulation results and experimental data indicate that it is necessary to consider the influence of sway motion on the anti-rolling tank, which is more agreeable to the actual circumstance.

  6. Anti-Candida and anti-Cryptococcus antifungal produced by marine microorganisms.

    Science.gov (United States)

    El Amraoui, B; El Amraoui, M; Cohen, N; Fassouane, A

    2014-12-01

    In order to search for antifungal from biological origin, we performed a screening of marine microorganisms isolated from seawater, seaweed, sediment and marine invertebrates collected from different coastal areas of the Moroccan Atlantic Ocean. The antifungal activities of these isolates were investigated against the pathogenic yeasts involved in medical mycology. Whole cultures of 34 marine microorganisms were screened for antifungal activities using the method of agar diffusion against four yeasts. The results showed that among the 34 isolates studied, 13 (38%) strains have antifungal activity against at least one out of four yeast species, 11 isolates have anti-Candida albicans CIP 48.72 activity, 12 isolates have anti-C. albicans CIP 884.65 activity, 13 isolates have anti-Cryptococcus neoformans activity and only 6 isolates are actives against Candida tropicalis R2 resistant to nystatin and amphotericin B. Nine isolates showed strong fungicidal activity. Fourteen microorganisms were identified and assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea, and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms could produce more antimicrobials; therefore these marine microorganisms were expected to be potential resources of natural products such as those we research: anti-Candida and anti-Cryptococcus fungicides.

  7. Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize

    Science.gov (United States)

    Adams, Stephen R.; Yang, Howard C.; Savariar, Elamprakash N.; Aguilera, Joe; Crisp, Jessica L.; Jones, Karra A.; Whitney, Michael A.; Lippman, Scott M.; Cohen, Ezra E. W.; Tsien, Roger Y.; Advani, Sunil J.

    2016-01-01

    Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery. PMID:27698471

  8. Development of syngeneic monoclonal anti-idiotype antibodies to mouse monoclonal anti-asialoglycoprotein receptor antibody.

    Directory of Open Access Journals (Sweden)

    Hirai M

    2002-06-01

    Full Text Available Anti-idiotype antibodies (Ab2 play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH. We previously developed a mouse monoclonal antibody (clone 8D7 which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1. One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1.

  9. Bioactivity screening of microalgae for antioxidant, anti-inflammatory, anticancer, anti-diabetes and antibacterial activities

    Directory of Open Access Journals (Sweden)

    Chiara eLauritano

    2016-05-01

    Full Text Available Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial and anti-biofilm activities. In addition, for two diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation and anti-biofilm (against the bacteria Staphylococcus epidermidis activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e. nutrient starvation conditions greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

  10. Hemolytic disease of the fetus and newborn caused by anti-E

    Directory of Open Access Journals (Sweden)

    Adiyyatu Sa′idu Usman

    2013-01-01

    Full Text Available Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

  11. Anti-allergic and anti-anaphylactic activities of Dolichos biflorus

    Directory of Open Access Journals (Sweden)

    Anupama Ashok Suralkar

    2013-01-01

    Full Text Available Background: The seeds of Dolichos biflorus (DB have been traditionally used in the treatment of cough and asthma. Aim: Based on the traditional claim, the present study was planned to evaluate the anti-allergic and anti-anaphylactic activities of DB. Materials and Methods: The ethanolic extract of the seeds of DB was prepared by cold maceration process. DB was subjected to phytochemical screening, acute toxicity studies, mast cell-stabilizing activity using compound 48/80 and anti-allergic activity using milk-induced leukocytosis and eosinophilia and passive paw anaphylaxis. Statistical Analysis: Statistical analysis was done by using one-way analysis of variance followed by Dunnett′s test. Results: The phytochemical investigation showed presence of proteins, flavonoids and glycosides. DB extract inhibited milk-induced leukocytosis and eosinophilia and also the compound 48/80 induced mast cell degranulation. DB extract significantly reduced passive paw anaphylaxis in a dose-dependent manner. Conclusion : The results demonstrated that DB extract possesses anti-allergic and anti-anaphylactic potentials that might be useful in the management of asthma.

  12. Anti-allergic and anti-inflammatory compounds from Aglaia andamanica leaves

    Directory of Open Access Journals (Sweden)

    Jindaporn Puripattanavong

    2015-02-01

    Full Text Available The leaves from Aglaia andamanica were determined for their anti-allergic and anti-inflammatory effects using RBL- 2H3 and RAW264.7 cells, respectively. Among the isolated compounds, 24-epi-piscidinol A (5 exhibited the highest antiallergic activity against -hexosaminidase release with an IC50 value of 19.8 M, followed by (--yangambin (3, IC50 = 33.8 M, pyramidaglain A (8, IC50 = 37.1 M, pachypodol (2, IC50 = 38.3 M and pyramidaglain B (9, IC50 = 44.8 M, respectively; whereas other compounds possessed moderate to mild effects (IC50 = 67.5->100 M. For anti-inflammatory activity, 24-epi-piscidinol A (5 possessed potent activity with an IC50 value of 24.0 M, followed by pyramidaglain B (9, IC50 = 25.6 M, pachypodol (2, IC50 = 34.5 M and (--yangambin (3, IC50 = 37.4 M, respectively; whereas other compounds exhibited moderate to mild activities (IC50 = 54.2->100 M. These active compounds could be developed as anti-allergic and anti-inflammatory agents in the future.

  13. Data of evolutionary structure change: 1ANTI-1E04L [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ANTI-1E04L 1ANT 1E04 I L ---------RDIPMNPMCIYRSPEKKATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFAMTKLGACNDTLQQLMEVFKFDTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFGDKSLTFNETYQDISE... 1ANT I 1ANTI AASTA--...4> 1ANT I 1ANTI ...line>VAL CA 395 1ANT I 1ANTI

  14. Data of evolutionary structure change: 1ANTI-1OYHL [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ANTI-1OYHL 1ANT 1OYH I L ---------RDIPMNPMCIYRSPEKKATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFAMTKLGACNDTLQQLMEVFKFDTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFGDKSLTFNETYQDISE...> 1ANT I 1ANTI AASTA...NT I 1ANTI IPMNPMCIYRS I 1ANTI RSPEKKATNRRV

  15. Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

    2007-05-15

    The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300-318 GeV using an integrated luminosity of 120 pb{sup -1}. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements. (orig.)

  16. ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF DELONIX ELATA BARK EXTRACTS

    Directory of Open Access Journals (Sweden)

    G. Murugananthan

    2011-06-01

    Full Text Available Delonix elata (D. elata, has long been used in traditional herbal medicine for the treatment of arthritis pain. In the present study an attempt was made to study the effect of D. elata barks for its anti-inflammatory and anti-arthritic effect in animal models. Barks were subjected for extraction with pet. ether, chloroform and 40% hydroalcohol successively and evaporated under rotary evaporator to get the concentrated extract. All the extracts were subjected for acute oral toxicity studies in rats and found to be safe up to the dose of 5g/kg body weight. Anti-inflammatory screening by carrageenan-induced paw oedema and cotton pellet induced granuloma method, the hydro alcohol extract of D. elata barks showed significant protection against the inflammation. In Complete Freund’s Adjuvant induced arthritis model also the hydro alcohol exhibited significant protection on day 7 onwards.

  17. Anti-S100A4 antibody suppresses metastasis formation by blocking stroma cell invasion

    DEFF Research Database (Denmark)

    Klingelhöfer, Jörg; Grum-Schwensen, Birgitte; Beck, Mette K

    2012-01-01

    The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... microenvironment, making it an attractive target for anti-cancer therapy. In this study, we produced a function-blocking anti-S100A4 monoclonal antibody with metastasis-suppressing activity. Antibody treatment significantly reduced metastatic burden in the lungs of experimental animals by blocking the recruitment...... its activity by suppressing stroma cell recruitment to the site of the growing tumor. Our epitope mapping studies suggested that the antibody recognition site overlaps with the target binding interface of human S100A4. We conclude here that this antibody could serve as a solid basis for development...

  18. Four dermatomyositis-specific autoantibodies-anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5-in adult and juvenile patients with idiopathic inflammatory myopathies in a Hungarian cohort.

    Science.gov (United States)

    Bodoki, Levente; Nagy-Vincze, Melinda; Griger, Zoltán; Betteridge, Zoe; Szöllősi, Lászlóné; Dankó, Katalin

    2014-12-01

    Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate

  19. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  20. Anti-inflammatory and anti-ulcerogenic activities of Chantaleela recipe.

    Science.gov (United States)

    Sireeratawong, Seewaboon; Khonsung, Parirat; Piyabhan, Pritsana; Nanna, Urarat; Soonthornchareonnon, Noppamas; Jaijoy, Kanjana

    2012-01-01

    Chantaleela recipe is indicated for relieving fever in Thai traditional folk medicine. In the present study, Chantaleela recipe was investigated for anti-inflammatory, analgesic, antipyretic and anti-ulcerogenic activities. In preliminary investigation Chantaleela recipe was found to exert an inhibitory activity on the acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema as well as in carrageenan-induced hind paw edema in rats. The results suggest that the anti-inflammatory activity of Chantaleela recipe may be due to an inhibition via cyclooxygenase pathway. In the analgesic test, Chantaleela recipe showed a significant analgesic activity in both the early and late phases of formalin test, but exerted the most pronounced effect in the late phase. The analgesic activity of Chantaleela recipe may act via mechanism at peripheral and partly central nervous system. In antipyretic test, Chantaleela recipe significantly decreased rectal temperature of brewer's yeast-induced hyperthermia rats, probably by inhibiting synthesis and/or release of prostaglandin E₂ in the hypothalamus. Therefore, the key mechanism of anti-inflammatory, analgesic, and antipyretic activity of the Chantaleela recipe likely involves the inhibition of the synthesis and/or release of inflammatory or pain mediators, especially prostaglandins. The oral administration of the Chantaleela recipe reduced ulcer formation in acute gastric ulcer models (EtOH/HCl-, indomethacin-, and stress-induced gastric lesions). In contrast, this recipe did not reduce the secretory rate, total acidity, and increase pH in rat stomach. These results indicated that Chantaleela seem to possess anti-ulcerogenic effect. This activity may be due to the increase of gastric mucosal resistance or potentiation of defensive factors and/or the decrease of aggressive factors but did not associate the anti-secretory activity. Moreover, the high oral doses treated did not cause acute toxicity in rats and the

  1. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities.

    Directory of Open Access Journals (Sweden)

    Ariane Leite Rozza

    Full Text Available The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg or menthol (50 mg/kg and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70 and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH, glutathione peroxidase (GSH-Px, glutathione reductase (GR and superoxide dismutase (SOD were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and the anti-inflammatory cytokine interleukin-10 (IL-10 were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.

  2. The gastroprotective effect of menthol: involvement of anti-apoptotic, antioxidant and anti-inflammatory activities.

    Science.gov (United States)

    Rozza, Ariane Leite; Meira de Faria, Felipe; Souza Brito, Alba Regina; Pellizzon, Cláudia Helena

    2014-01-01

    The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.

  3. Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats.

    Science.gov (United States)

    Albayrak, Abdulmecit; Polat, Beyzagul; Cadirci, Elif; Hacimuftuoglu, Ahmet; Halici, Zekai; Gulapoglu, Mine; Albayrak, Fatih; Suleyman, Halis

    2010-01-01

    In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.

  4. Anti-allergic and anti-inflammatory compounds from Aglaia andamanica leaves

    OpenAIRE

    Jindaporn Puripattanavong; Supinya Tewtrakul

    2015-01-01

    The leaves from Aglaia andamanica were determined for their anti-allergic and anti-inflammatory effects using RBL- 2H3 and RAW264.7 cells, respectively. Among the isolated compounds, 24-epi-piscidinol A (5) exhibited the highest antiallergic activity against -hexosaminidase release with an IC50 value of 19.8 M, followed by (-)-yangambin (3, IC50 = 33.8 M), pyramidaglain A (8, IC50 = 37.1 M), pachypodol (2, IC50 = 38.3 M) and pyramidaglain B (9, IC50 = 44.8 M), respectively; ...

  5. Anti-S. typhi Vi IgG levels in children with and without typhoid vaccinations

    Directory of Open Access Journals (Sweden)

    Sriandayani

    2014-09-01

    Full Text Available Background Typhoid fever is endemic to Indonesia, with an annual incidence of 13/10,000 people. Vaccination has been shown to be an effective method to prevent typhoid fever. Of several vaccine types, the polysaccharide Vi vaccine is the most commonly used typhoid vaccine in developing countries. Results of previous studies remain inconclusive on the necessity of revaccination every 3 years. Objective To compare the mean serum antibody titers of anti-S. typhi Vi IgG and the proportion of children with protective antibody levels between children with and without typhoid Vi vaccination. Methods We conducted a cross-sectional study at Tuminting District, Manado from June to September 2012. Data was analyzed using independent T-test and Fisher’s test. Serum anti-S. typhi Vi IgG levels were measured by enzyme-linked immunosorbent assay (ELISA method. Results Seventy-six subjects were divided into two groups: 38 children who had received the typhoid Vi vaccination more than 3 years prior to this study and 38 children who never had typhoid vaccinations as a control group. No statistically significant difference in age and gender was found between the two groups. The mean serum anti-Vi IgG level was 0.55 ug/mL (SD 0.58; 95%CI 0.36 to 0.74 in the vaccinated group, significantly higher than that of the control group [0.31 ug/mL (SD 0.42; 95%CI 0.17 to 0.44; P=0.038]. The proportion of children with protective anti-Vi antibody level was higher in the vaccinated group (23.7% than in the control group (10.5%, however, this difference was not statistically significant (P=0.128. Conclusion The mean serum anti-S. typhi Vi IgG antibody level in children who had been vaccinated more than 3 years prior to the study is higher than in children who had never received typhoid vaccinations. Nevertheless, the mean antibody titers are generally non-protective in both groups. Also, the proportion of children with protective antibody levels is not significantly different

  6. PTU-associated cutaneous vasculitis with ANCA anti-MPO and anti-PR3 antibodies.

    Science.gov (United States)

    Jacobs, E M G; Hartkamp, A; Kaasjager, H A H

    2003-09-01

    A 36-year-old woman presented at our clinic with symmetrical, tender, palpable purpuric lesions on her lower legs and buttocks after restarting PTU therapy for relapsing Graves' disease. PTU-induced vasculitis was diagnosed with remarkable ANCA anti-MPO and anti-PR3 antibody positivity. The purpuric skin lesions resolved immediately after discontinuation of the drug and the ANCA titres lowered. In the presence of activated neutrophils, PTU could induce a high cytotoxity and injure the vessel walls. Treatment of choice is discontinuation of the drug. Sometimes more aggressive therapy as cyclophosphamide or plasmapheresis is warranted.

  7. Treating asthma with anti-IgE or anti-IL5.

    Science.gov (United States)

    Lötvall, J; Pullerits, T

    1999-10-01

    In the last decades, several key mechanisms driving asthma pathophysiooogy have been discovered. These include the role of IgE in allergic disease, and the role of IL-5 in eosinophilic inflammation. In the last few years, tools to block each of these have been developed. At this time, early clinical studies with neutralizing antibodies against both IgE and IL-5 have been performed in asthma patients, with promising results, and larger studies are underway. The mechanisms of, and possible role of, both anti-IgE and anti-IL-5 treatment in asthma are discussed in this review article.

  8. Anti-Angiogenesis and Anti-Tumor Effect of Shark Cartilage Extract

    Institute of Scientific and Technical Information of China (English)

    王锋; 王漪涛; 谢莉萍; 张荣庆

    2001-01-01

    The effect of shark cartilage extract (SCE), purified in this laboratory, on angiogenesis in chick chorioallantoic membrane (CAM), on the activity of collagenase IV and on human umbilical vein endothelial cell (ECV-304) proliferation and apoptosis was investigated in vitro. The results showed that SCE caused a decline in CAM blood vessels and significantly prevented collagenase-induced collagenolysis. Moreover, SCE produced a dose-dependent decline in ECV-304 proliferation and altered its normal cell cycle. These results suggest that the anti-angiogenesis and anti-tumor effects of shark cartilage may be due to inhibition of endothelial cells as well as collagenolysis.

  9. Anti-reflective and anti-soiling coatings for self-cleaning properties

    Energy Technology Data Exchange (ETDEWEB)

    Brophy, Brenor L.; Nair, Vinod; Dave, Bakul Champaklal

    2016-05-31

    The disclosure discloses abrasion resistant, persistently hydrophobic and oleophobic, anti-reflective and anti-soiling coatings for glass. The coatings described herein have wide application, including for example the front cover glass of solar modules. Methods of applying the coatings using various apparatus are disclosed. Methods for using the coatings in solar energy generation plants to achieve greater energy yield and reduced operations costs are disclosed. Coating materials are formed by combinations of hydrolyzed silane-base precursors through sol-gel processes. Several methods of synthesis and formulation of coating materials are disclosed.

  10. Novel anti-inflammatory agents in COPD

    DEFF Research Database (Denmark)

    Loukides, Stelios; Bartziokas, Konstantinos; Vestbo, Jørgen

    2013-01-01

    Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase...... on these strategies exist at the moment. A third potential approach involves novel agents whose mechanism of action is closely related to COPD mechanisms and pathophysiology. Such novel treatments are of great interest since they may treat both COPD and co-morbidities. Several novel agents are currently under...

  11. Anti-Ageing Cultures, Biopolitics and Globalisation

    Directory of Open Access Journals (Sweden)

    Brett Neilson

    2011-11-01

    Full Text Available In March 2004, the author attended the Inaugural International Conference on Longevity at the Sydney Exhibition and Convention Centre in Darling Harbour. As a cultural researcher interested in the interactions between demographic shifts, capitalist globalisation and changing forms of political power, the prospect of a direct encounter with the debates and practices surrounding the burgeoning field of anti-ageing medicine promised a means to observe the complex cultural dynamics of population ageing at play. This article explores the discord the atuhor witnessed; a quarrel that, despite the march of technological advance, attests the ongoing conflict in the nexus where politics meets life.

  12. Erdosteine: antitussive and anti-inflammatory effects.

    Science.gov (United States)

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  13. Supersymmetry in anti-de Sitter space

    Energy Technology Data Exchange (ETDEWEB)

    Burges, C.J.C.; Freedman, D.Z.; Davis, S.; Gibbons, G.W.

    1986-04-01

    We consider the Wess-Zumino model in a background anti-de Sitter space-time in four dimensions (AdS)/sub 4/. We show that the naive generators of the O(3,2) isometry group, obtained by the Noether method, must be improved by adding surface terms. The improved generators have a manifestly positive definite energy density, are conserved, and have vanishing expectation value in a supersymmetric vacuum. The naive generators enjoy none of these properties. Propagators for scalar and spinor fields in (Ad S)/sub 4/ are presented, and a simple derivation of the trace anomaly is given.

  14. Anti-thrombotic technologies for medical devices.

    Science.gov (United States)

    Lavery, Karen S; Rhodes, Candace; Mcgraw, Adam; Eppihimer, Michael J

    2016-08-03

    Thrombosis associated with medical devices may lead to dramatic increases in morbidity, mortality and increased health care costs. Innovative strategies are being developed to reduce this complication and provide a safe biocompatible interface between device and blood. This article aims to describe the biological phenomena underlying device-associated thrombosis, and surveys the literature describing current and developing technologies designed to overcome this challenge. To reduce thrombosis, biomaterials with varying topographical properties and incorporating anti-thrombogenic substances on their surface have demonstrated potential. Overall, there is extensive literature describing technical solutions to reduce thrombosis associated with medical devices, but clinical results are required to demonstrate significant long-term benefits.

  15. A Tale of Two Anti-Americanisms

    Directory of Open Access Journals (Sweden)

    Pierre Guerlain

    2007-11-01

    Full Text Available There is, of course no single American tradition or single American set of values. There are, and always have been, many Americas. We each of us remember and appeal to the Americas we prefer.Immanuel WallersteinWhat does the term mean? That you’re anti-jazz? Or that you’re opposed to free speech? That you don’t delight in Toni Morrison or John Updike? That you have a quarrel with giant sequoias? Does it mean that you don’t admire the hundreds of thousands of American citizens who marched agai...

  16. Retinal Vasculitis in Anti-Synthetase Syndrome.

    Science.gov (United States)

    Donovan, Christopher P; Pecen, Paula E; Baynes, Kimberly; Ehlers, Justis P; Srivastava, Sunil K

    2016-09-01

    A 31-year-old woman with a history of anti-synthetase syndrome-related myositis and interstitial lung disease presented with acute-onset blurry vision and rash on her hands and feet. Visual acuity was hand motion in her right eye and 20/40 in her left eye. Dilated fundus exam showed extensive retinal vasculitis, diffuse intraretinal hemorrhages, and subretinal fluid. Optical coherence tomography revealed significant macular thickening, and fluorescein angiography revealed vascular leakage with peripheral nonperfusion. Aggressive systemic immunosuppression was initiated, with gradual resolution of her disease during 8 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:874-879.].

  17. Optical "anti-transient" detected by MASTER

    Science.gov (United States)

    Denisenko, D.; Gorbovskoy, E.; Lipunov, V.; Balanutsa, P.; Yecheistov, V.; Tiurina, N.; Kornilov, V.; Belinski, A.; Shatskiy, N.; Chazov, V.; Kuznetsov, A.; Zimnukhov, D.; Krushinsky, V.; Zalozhnih, I.; Popov, A.; Bourdanov, A.; Punanova, A.; Ivanov, K.; Yazev, S.; Budnev, N.; Konstantinov, E.; Chuvalaev, O.; Poleshchuk, V.; Gress, O.; Parkhomenko, A.; Tlatov, A.; Dormidontov, D.; Senik, V.; Yurkov, V.; Sergienko, Y.; Varda, D.; Sinyakov, E.; Shurpakov, S.; Shumkov, V.; Podvorotny, P.; Levato, H.; Saffe, C.; Mallamaci, C.; Lopez, C.; Podest, F.

    2013-02-01

    We have started the search for the disappearing stars (optical "anti-transients", OATs) in the MASTER database. The first result is the detection of a deep (~3.5 magnitudes) fading of the bright star TYC 2505-672-1 whose variability was previously unknown. This star has the coordinates 09 53 10.00 +33 53 52.7 and magnitudes V=10.71, B=12.51 in Tycho2 catalogue and J=7.61, H=6.78, K=6.57 in 2MASS.

  18. Anti-resonant hexagram hollow core fibers.

    Science.gov (United States)

    Hayes, John R; Poletti, Francesco; Abokhamis, Mousavi S; Wheeler, Natalie V; Baddela, Naveen K; Richardson, David J

    2015-01-26

    Various simple anti-resonant, single cladding layer, hollow core fiber structures are examined. We show that the spacing between core and jacket glass and the shape of the support struts can be used to optimize confinement loss. We demonstrate the detrimental effect on confinement loss of thick nodes at the strut intersections and present a fabricated hexagram fiber that mitigates this effect in both straight and bent condition by presenting thin and radially elongated nodes. This fiber has loss comparable to published results for a first generation, multi-cladding ring, Kagome fiber with negative core curvature and has tolerable bend loss for many practical applications.

  19. Development of Anti-Isoproturon Polyclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    LI Fang-shi; SUN Feng; LIU Xian-jin; CUI Heng-hua

    2007-01-01

    A competitive enzyme-linked immunosorbent assay (ELISA) suitable for the determination of the urea herbicide isoproturon,3-(4-isopropylphenyl)-1,1-dimethylurea, in food and environmental samples was developed. Two haptens named 1-(3-carboxypropyl)-3-(4-isopropylphenyl)-1-methylurca (hapten 4C) and 1-(5-carboxypentyl)-3-(4-isopropylphenyl)-1-methylurea (hapten 6C) were synthesized. The haptens were coupled to bovine serum albumin (BSA) and ovalbumin(OVA), respectively, using the N-hydroxysuccinimide reaction. The hapten 6C-BSA conjugate was used as the immunogen,with which a high-titer anti-isoproturon polyclonal antibody (pAb) was successfully obtained by immunization of New Zealand white rabbits. The hapten 4C-OVA conjugate was used as coating antigen and a method of the indirect competitive ELISA for isoproturon was established. The haptens were confirmed with TLC, IR, and 1H NMR. The conjugation molar ratios of hapten 4C to OVA and hapten 6C to BSA were 36:1 and 46:1, respectively, as calculated by a UV spectrophotometry.The highest titer of the anti-isoproturon sera determined by a non-competitive indirect ELISA procedure was 1.6×105. The optimal concentrations of the coating antigen and the dilution of the anti-isoproturon sera used in the ELISA were 0.1 mg L-1 and 1.0 × 105, respectively. The concentration of isoproturon that inhibits 50% of antibody-antigen binding (IC50) was 0.07 mg mL-1.The cross-reactivities of six urea herbicides including chlorbromuron, fluometuron, monolinuron were lower than 0.1%. Isoproturon is a small molecule without immune activity and active functional group for attaching to carrier protein. To produce an antibody against isoproturon with high titer and high specificity is the most important step in the development of an immunochemical method for the determination of isoproturon in food and environmental samples. The two haptens synthesized in this study have carboxyl groups and accommodate different lengths of spacer arms, and

  20. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study

    NARCIS (Netherlands)

    Bartelds, G.M.; Wijbrandts, C.A.; Nurmohamed, M.T.; Stapel, S.; Lems, W.F.; Aarden, L.; Dijkmans, B.A.C.; Tak, P.P.; Wolbink, G.J.

    2010-01-01

    OBJECTIVE: To investigate how antibodies against anti-tumour necrosis factor (anti-TNF) agents influence response after switching from infliximab to adalimumab in rheumatoid arthritis (RA). METHODS: This cohort study consisted of 235 patients with RA, all treated with adalimumab. At baseline 52 pati

  1. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity.

    Science.gov (United States)

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; Khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect.

  2. Studies on the anti-inflammatory and anti-nociceptive properties of Blepharis maderaspatensis leaves

    Directory of Open Access Journals (Sweden)

    Abimbola Sowemimo

    2013-10-01

    Full Text Available Blepharis maderaspatensis(L. B. Heyne ex Roth, Acanthaceae, is a procumbent or scrambling perennial herb used traditionally for treatment of snakebites, wounds, edema and gout. The anti-inflammatory and anti-nociceptive properties of the ethanol extract of the whole plant of B. maderaspatensis was investigated using carrageenan-induced paw edema in rats, xyleneinduced edema in mice, mouse writhing and tail clip tests respectively. The effect of the extract on inflammatory mediators, serotonin and histamine, using the most active dose (75 mg/kg was also carried out. The results showed that the extract of B. maderaspatensis in carrageenan-induced test caused a significant inhibition (84.5%, 90 min of paw edema at a dose of 75 mg/kg while the xylene-induced test caused a significant inhibition (62.65% at 50 mg/kg. The histamine-induced test showed significant inhibition (90.9%, 90 min while serotonin-induced test showed moderate inhibition (54.10%, 180 min. In the mouse writhing and tail clip tests, the extract produced a significant inhibition of 66.21% and 15.81% at 75 mg/kg, respectively. These results collectively demonstrate that the ethanol extract of B. maderaspatensis possesses anti-inflammatory and anti-nociceptive properties, and this supports the ethnopharmacological use of the plant in the treatment of inflammation.

  3. Anti-cyclic Citrullinated Peptide Antibody (Anti-CCP and Diagnostic Value for Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mehmet Agilli

    2014-02-01

    Full Text Available Rheumatoid arthritis (RA is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;s prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [TAF Prev Med Bull 2014; 13(1.000: 83-88

  4. Anti-hepatotoxic and anti-oxidant defense potential of Tridax procumbens

    Directory of Open Access Journals (Sweden)

    Hemalatha Reddipalli

    2008-01-01

    Full Text Available Tridax procumbens is a widely occurring medicinal herb used by ethnomedical practitioners. With increased use of chemicals and alcohol besides growing incidence of viruses and autoimmune diseases, the incidence of liver injury is growing for which conventional drugs used for treatment are often inadequate. Various models are adopted in pharmological studies for inducing hepatitis/ liver injury similar to those observed in human viral hepatitis, diabetes and oxidative stress. D-galactosamine with lipopolysacchride (LPS, carbontetrachloride (CCl 4 and paracetamol intoxication, diabetes induced with alloxan are widely used on rodents for this purpose. In vitro studies on Tridax procumbens (TP revealed the anti-oxidant potential of the herb with chloroform fraction of the ethanolic extract showing maximum activity. It is also reported to possess anti-oxidant minerals such as iron, magnesium, copper and zinc. In vivo studies on rodents on the anti-oxidant potential of TP induced through LPS, CCl 4, alloxan and paracetamol intoxication induced hepatitis confirmed the results from in vitro studies as a potential anti-hepatotoxic herb.

  5. Anti Moppel : logistikafirmadel ei tasu ELi karta / Anti Moppel ; interv. Rivo Sarapik

    Index Scriptorium Estoniae

    Moppel, Antti, 1968-

    2003-01-01

    Ilmunud ka: Delovõje Vedomosti : Avtomobili i transport 15. okt. lk. 10-11. Majandus- ja kommunikatsiooniministeeriumi osakonnajuhataja Anti Moppel vastab küsimustele, mis puudutavad logistikafirmade ootusi EL-ist, Eesti transpordituru arengut, transpordifirmade valmisolekut Eesti liitumiseks EL-iga, ministeeriumi pakutavat infot EL-i kohta

  6. Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Yue Jing

    2015-04-01

    Full Text Available Fifteen semi-synthetic derivatives of asiatic acid (AA have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3, while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4–10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11–17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.

  7. The anti-obesity drug orlistat reveals anti-viral activity.

    Science.gov (United States)

    Ammer, Elisabeth; Nietzsche, Sandor; Rien, Christian; Kühnl, Alexander; Mader, Theresa; Heller, Regine; Sauerbrei, Andreas; Henke, Andreas

    2015-12-01

    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways.

  8. Combined Anti-PLGF and Anti-Endostatin Treatments Inhibit Ocular Hemangiomas

    Directory of Open Access Journals (Sweden)

    Hua Jiang

    2015-06-01

    Full Text Available Background/Aims: The degree of neovascularization determines the aggressiveness of ocular hemangiomas (OH. So far, the anti-angiogenic treatments using either antagonists against vascular endothelial growth factor A (VEGF-A, or endostatin, do not always lead to satisfactory therapeutic outcome. Methods: We examined the VEGF receptor 1 (VEGFR1 levels in the OH specimen. We compared the effects of anti-PLGF, endostatin, as well as their combined treatments on the growth of OH in a mouse model, using bioluminescence imaging in living animals. We also examined vascularization by CD31 expression. Results: We detected higher VEGFR1 levels in the OH, compared to paired normal tissue. Thus, we hypothesize that as a major ligand for VEGFR1, placental growth factor (PLGF may also play a role in the neovascularization and tumorigenesis of OH. In an implanted OH model in mice, we found that both anti-PLGF and endostatin significantly decreased OH growth as well as vascularization, while combined treatments had a significantly more pronounced effect. Conclusion: Our data suggest that combined anti-PLGF and endostatin may be a more effective therapy for inhibition of ocular vascularization and the tumor growth in OH.

  9. [Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update].

    Science.gov (United States)

    Pozdzik, A A; Debiec, H; I Brochériou; Husson, C; Rorive, S; Broeders, N; Le Moine, A; Ronco, P; Nortier, J

    2015-01-01

    Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined.

  10. Farmacoeconomic impact of anti-TNFα

    Directory of Open Access Journals (Sweden)

    E. Vaccaro

    2011-09-01

    Full Text Available The anti-TFNα are undoubtedly an efficacious cure in the treatment of rheumatoid arthritis, but their costs are so high that a thorough pharmacoeconomical evaluation is needed in order to identify the specific conditions in which their use is to be considered convenient. For this reason there are related the most important experiences that have studied the cost-efficacy and cost-utility relationships of anti-TFNα drugs, which have been made marketable in Italy. The data available, unfortunately, are too various to allow a final settlement of the chart of convenience between the different therapeutic alternatives. Moreover the socio-medical reality in Italy is so much different from the ones in other countries that it is impossible to try and use the foreign experiences. In a country of high social commitment like Italy, a fair judgment can thereafter be made only when the issue is considered related to our society, taking in account the summation of the medical costs endured by the National Health System, the patient’s expenses and the ones that are a consequence of the loss of productivity.

  11. Compression station anti-surge system considerations

    Energy Technology Data Exchange (ETDEWEB)

    Kurz, Rainer; White, Robert C. [Solar Turbines Incorporated, Houston, TX (United States)

    2005-07-01

    Centrifugal compressor surge and its prevention have drawn significant attention in the literature. An important aspect of surge avoidance lies in the design of the compressor station and, in particular, the piping upstream and downstream of the compressor. Most anti-surge systems are perfectly capable of avoiding surge during normal operating conditions. However, unplanned emergency shutdowns present a significant challenge, and surge avoidance in these cases depends to a large degree on the station layout. Furthermore, the concepts used in the anti surge system (valves, piping, coolers) also impact the start-up of the station, or of individual units of the station. In this paper a simplified surge control system model is presented and used to develop simpler rules that help with proper sizing of upstream and downstream piping systems, as well as the necessary control element. Since the design of the surge control and recycle system also affects the start-up of units and stations, start-up considerations for stations with and without cooled recycle loops are discussed. (author)

  12. Immunomodulatory effects of anti-microbial peptides.

    Science.gov (United States)

    Otvos, Laszlo

    2016-09-01

    Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro- and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

  13. Anti IH: An antibody worth mention.

    Science.gov (United States)

    Mohanan, Nithya; Henry, Nittin; Rafi, Aboobacker Mohamed; Innah, Susheela J

    2016-01-01

    A 72-year-old female with co-morbidities posted for surgical correction of fracture neck of femur without any history of transfusions was noted to have a hemoglobin level of 7 g/dl and packed red blood cells transfusion was ordered. Pretransfusion tests demonstrated A1B group with D positive on forward grouping. Reverse grouping showed a varying grade of agglutination with A, B, and O cells. Agglutination being stronger at 4°C. Antibody screening showed pan-agglutination, direct Coomb's test and auto control were negative. The serum reacted with adult O cells (OIadult) but not with adult Bombay cells (Oh Iadult) or O cord (Oicord) cells. A possibility of a compound cold antibody anti IH was made and A1B compatible cells were transfused to the patient. This case report illustrates anti-IH cold agglutinin with broad thermal amplitude. Uniqueness of this case report was O group incompatibility with A1B group, which was detected earlier and a catastrophic transfusion reaction being subverted.

  14. Anti IH: An antibody worth mention

    Directory of Open Access Journals (Sweden)

    Nithya Mohanan

    2016-01-01

    Full Text Available A 72-year-old female with co-morbidities posted for surgical correction of fracture neck of femur without any history of transfusions was noted to have a hemoglobin level of 7 g/dl and packed red blood cells transfusion was ordered. Pretransfusion tests demonstrated A1B group with D positive on forward grouping. Reverse grouping showed a varying grade of agglutination with A, B, and O cells. Agglutination being stronger at 4°C. Antibody screening showed pan-agglutination, direct Coomb's test and auto control were negative. The serum reacted with adult O cells (OIadult but not with adult Bombay cells (Oh Iadult or O cord (Oicord cells. A possibility of a compound cold antibody anti IH was made and A1B compatible cells were transfused to the patient. This case report illustrates anti-IH cold agglutinin with broad thermal amplitude. Uniqueness of this case report was O group incompatibility with A1B group, which was detected earlier and a catastrophic transfusion reaction being subverted.

  15. Magnetospheric "anti-glitches" in magnetars

    CERN Document Server

    Lyutikov, Maxim

    2013-01-01

    We attribute the rapid spindown of magnetar 1E 2259+586 observed by Archibald et al. (2013), termed the "anti-glitch", to partial opening of the magnetosphere during the X-ray burst, followed by changes of the structure of the closed field line region. To account for the observed spin decrease during the X- ray flare all that is needed is the transient opening, for just one period, of a relatively small fraction of the magnetosphere, of the order of only few percent. More generally, we argue that in magnetars all timing irregularities have magnetospheric origin and are induced either by (i) the fluctuations in the current structure of the magnetosphere (similar to the long term torque variations in the rotationally powered pulsars); or, specifically to magnetars, by (ii) opening of a fraction of the magnetosphere during bursts and flares - the latter events are always accompanied by rapid spindown, an "anti-glitch". Slow rotational motion of the neutron star crust, driven by crustal magnetic fields, leads bey...

  16. Nonsteroid Anti-inflammatory Drugs and Kidney

    Directory of Open Access Journals (Sweden)

    Yaşar Yıldırım1

    2016-03-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are often used in the treatment of chronic and acute pain and inflammation as an analgesic and anti-inflammatory agent. They inhibit the synthesis of prostaglandins which have influence on glomerular capillaries, vasa recta and tubular functions. They lead to significant complications such as hyperkalemia, hyponatremia, edema and hypertension. Usage of NSAIDs is a risk factor for acute kidney injury in some conditions such as advanced age, dehydration, vomiting, diuretics, ACE/ARB therapy, heart failure, nephrotic syndrome, cirrhosis and chronic kidney disease. Acute interstitial nephritis is not dependent on the drug dose and it is characterized by immunological inflammatory reaction and a decrease in creatinine clearance. Besides the classical findings, glomerules can be involved and minimal change disease or membranous glomerulonephritis can develop. Analgesic nephropathy is characterized by interstitial nephritis and papillary necrosis. Metabolites of NSAIDs are accumulated in renal medulla which has lowest oxygen pressure in kidney and they disrupt the renal parencymal perfusion by vasoconstriction. Respectively, papillar necrosis, glomerular sclerosis, interstitial fibrosis and cortical atrophy can develop insidiously.

  17. Geldanamycin and its anti-cancer activities.

    Science.gov (United States)

    Fukuyo, Yayoi; Hunt, Clayton R; Horikoshi, Nobuo

    2010-04-01

    Geldanamycin is a benzoquinone ansamycin antibiotic that manifests anti-cancer activity through the inhibition of HSP90-chaperone function. The HSP90 molecular chaperone is expressed at high levels in a wide variety of human cancers including melanoma, leukemia, and cancers in colon, prostate, lung, and breast. In cancer cells dependent upon mutated and/or over-expressed oncogene proteins, HSP90 is thought to have a critical role in regulating the stability, folding, and activity of HSP90-associated proteins, so-called "client proteins". These client proteins include the growth-stimulating proteins and kinases that support malignant transformation. Recently, oncogenic activating BRAF mutants have been identified in variety of cancers where constitutive activation of the MEK/ERK MAPK signaling pathway is the key for tumorigenesis, and they have been shown to be client proteins for HSP90. Accordingly, HSP90 inhibition can suppress certain cancer-causing client proteins and therefore represents an important therapeutic target. The molecular mechanism underlying the anti-cancer effect of HSP90 inhibition is complicated. Geldanamycin and its derivatives have been shown to induce the depletion of mutationally-activated BRAF through several mechanisms. In this review, we will describe the HSP90-inhibitory mechanism, focusing on recent progress in understanding HSP90 chaperone structure-function relationships, the identification of new HSP90 client proteins and the development of HSP90 inhibitors for clinical applications.

  18. High gain durable anti-reflective coating

    Energy Technology Data Exchange (ETDEWEB)

    Maghsoodi, Sina; Brophy, Brenor L.; Colson, Thomas E.; Gonsalves, Peter R.; Abrams, Ze' ev R.

    2016-07-26

    Disclosed herein are polysilsesquioxane-based anti-reflective coating (ARC) compositions, methods of preparation, and methods of deposition on a substrate. In one embodiment, the polysilsesquioxane of this disclosure is prepared in a two-step process of acid catalyzed hydrolysis of organoalkoxysilane followed by addition of tetralkoxysilane that generates silicone polymers with >40 mol % silanol based on Si-NMR. These high silanol siloxane polymers are stable and have a long shelf-life in polar organic solvents at room temperature. Also disclosed are low refractive index ARC made from these compositions with and without additives such as porogens, templates, thermal radical initiator, photo radical initiators, crosslinkers, Si--OH condensation catalyst and nano-fillers. Also disclosed are methods and apparatus for applying coatings to flat substrates including substrate pre-treatment processes, coating processes and coating curing processes including skin-curing using hot-air knives. Also disclosed are coating compositions and formulations for highly tunable, durable, highly abrasion-resistant functionalized anti-reflective coatings.

  19. Optical enhancing durable anti-reflective coating

    Energy Technology Data Exchange (ETDEWEB)

    Maghsoodi, Sina; Varadarajan, Aravamuthan; Movassat, Meisam

    2016-07-05

    Disclosed herein are polysilsesquioxane based anti-reflective coating (ARC) compositions, methods of preparation, and methods of deposition on a substrate. In embodiments, the polysilsesquioxane of this disclosure is prepared in a two-step process of acid catalyzed hydrolysis of organoalkoxysilane followed by addition of tetralkoxysilane that generates silicone polymers with >40 mol % silanol based on Si-NMR. These high silanol siloxane polymers are stable and have a long shelf-life in the polar organic solvents at room temperature. Also disclosed are low refractive index ARC made from these compositions with and without additives such as porogens, templates, Si--OH condensation catalyst and/or nanofillers. Also disclosed are methods and apparatus for applying coatings to flat substrates including substrate pre-treatment processes, coating processes including flow coating and roll coating, and coating curing processes including skin-curing using hot-air knives. Also disclosed are coating compositions and formulations for highly tunable, durable, highly abrasion-resistant functionalized anti-reflective coatings.

  20. Pharmacogenetics of Anti-Diabetes Drugs

    Directory of Open Access Journals (Sweden)

    Johanna K. DiStefano

    2010-08-01

    Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

  1. Pharmacogenetics of Anti-Diabetes Drugs.

    Science.gov (United States)

    Distefano, Johanna K; Watanabe, Richard M

    2010-08-01

    A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of 'response' can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for "individualized medicine" for patients with T2D.

  2. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  3. Evaluation of anti-oxidant and anti-cancer properties of Dendropanax morbifera Léveille.

    Science.gov (United States)

    Hyun, Tae Kyung; Kim, Myeong-ok; Lee, Hyunkyoung; Kim, Younjoo; Kim, Euikyung; Kim, Ju-Sung

    2013-12-01

    Dendropanax morbifera Léveille, an endemic species in Korea, is best known as a tree that produces a resinous sap. Although D. morbifera is used in folk medicine, its biological activities are poorly understood. In this study, the methanolic extracts of D. morbifera branches, debarked stems, bark, and two different stages of leaves were evaluated for anti-oxidant activity and anti-cancer potential. The debarked stem extract exhibited strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and reducing power compared with other samples. In addition, the cytotoxic activities of these extracts were investigated in human tumour cell lines. The results suggested that the extracts of debarked stems, green leaves, and yellow leaves were the potent source of anti-cancer compounds, particularly in Huh-7 cells. Furthermore, treatment with the extracts of debarked stems, green leaves, and yellow leaves caused an increase of apoptotic or senescent cells in Huh-7 cells. Twenty-four hour treatment with debarked stems extract resulted in the strong induction of p53 and p16, whereas both leaf extracts inhibited the activation of ERK. The debarked stems and green leaf extracts reduced Akt levels in Huh-7 cells, indicating that D. morbifera extracts caused the activation of p16 and p53 pathways. This, together with the inhibition of Akt or ERK signalling, resulted in suppression of Huh-7 cell proliferation. These results suggest that methanolic leaf and debarked stems extracts are a source of anti-oxidant and anti-cancer compounds, and could be developed as a botanical drug.

  4. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    Institute of Scientific and Technical Information of China (English)

    Parastoo Karimian; Gholamreza Kavoosi; Zahra Amirghofran

    2014-01-01

    Objective:To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods:In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-αmRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results:Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 μg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-αmRNA expression in the cells at concentrations of 50 μg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions:T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions.

  5. [A spectrum of neurological diseases with anti-VGKC antibody].

    Science.gov (United States)

    Arimura, Kimiyoshi; Watanabe, Osamu; Nagado, Tatsui

    2007-11-01

    Anti-VGKC antibody causing peripheral nerve hyperexcitability is already an established clinical entity. Recently, many patients with non-herpetic limbic encephalitis (NHLE) with anti-VGKC antibody have been reported. The characteristic clinical features are low serum Na+ concentration and good response to immunotherapy. Anti-VGK antibody positive NHLE is relatively frequent among immune-mediated NHLE. It is important to know that this disease is responsive to immunotherapy. Furthermore, anti-VGKC antibody is also positive in some intractable epilepsies. These findings suggest that anti-VGKC is correlated with hyperexcitability in both the peripheral and central nervous system and that the spectrum of anti-VGKC antibody syndrome is now expanding.

  6. Pre-Stressed Rope Reinforced Anti-Sliding Pile

    Institute of Scientific and Technical Information of China (English)

    XU Jun; WANG Chenghua

    2006-01-01

    Pre-stressed rope reinforced anti-sliding pile is a composite anti-sliding structure. It is made up of pre-stressed rope and general anti-sliding pile. It can bring traditional anti-sliding pile's retaining performance into full play, and to treat with landslide fast and economically. The difference between them is that the pre-stressed rope will transfix the whole anti-sliding pile through a prearranged pipe in this structure. The working mechanics, the design method and economic benefit are studied. The results show that the pre-stressed rope reinforced anti-sliding pile can treat with the small and middle landslides or high slopes well and possess the notable advantage of technology and economic.

  7. Anti-aging cosmetics and its efficacy assessment methods

    Science.gov (United States)

    Li, Xiang

    2015-07-01

    The mechanisms of skin aging, the active ingredients used in anti-aging cosmetics and evaluation methods for anti-aging cosmetics were surmised in this paper. And the mechanisms of skin aging were introduced in the intrinsic and extrinsic ways. Meanwhile, the anti-aging cosmetic active ingredients were classified in accordance with the mechanism of action. Various evaluation methods such as human evaluation, in vitro evaluation were also summarized.

  8. The anti-cancer activity of noscapine: a review.

    Science.gov (United States)

    Mahmoudian, Massoud; Rahimi-Moghaddam, Parvaneh

    2009-01-01

    Noscapine is an isoqiunoline alkaloid found in opium latex. Unlike most other alkaloids obtained from opium latex, noscapine is not sedative and has been used as antitussive drug in various countries. Recently, it has been introduced as an anti-mitotic agent. This drug can be used orally. When the resistance to other anti-cancer drugs such as paclitaxel manifests, noscapine might be effective. Therefore, noscapine and its analogs have great potential as novel anti-cancer agents.

  9. Spin flips and quantum information for anti-parallel spins

    CERN Document Server

    Gisin, Nicolas

    1999-01-01

    We consider two different ways to encode quantum information, by parallel or anti-parallel pairs of spins. We find that there is more information in the anti-parallel ones. This purely quantum mechanical effect is due to entanglement, not of the states but occuring in the course of the measuring process. We also introduce a range of quantum information processing machines, such as spin-flip and anti-cloning.

  10. A Review on Anti-Inflammatory Activity of Monoterpenes

    Directory of Open Access Journals (Sweden)

    Damião Pergentino de Sousa

    2013-01-01

    Full Text Available Faced with the need to find new anti-inflammatory agents, great effort has been expended on the development of drugs for the treatment of inflammation. This disorder reduces the quality of life and overall average productivity, causing huge financial losses. In this review the anti-inflammatory activity of 32 bioactive monoterpenes found in essential oils is discussed. The data demonstrate the pharmacological potential of this group of natural chemicals to act as anti-inflammatory drugs.

  11. In Vitro Anti-Candida Activity of Zataria multiflora Boiss

    OpenAIRE

    Ali Zarei Mahmoudabadi; Muhammad Ali Dabbagh; Zahra Fouladi

    2006-01-01

    Zataria multiflora Boiss known as Avishan Shirazi (in Iran) is one of the valuable Iranian medicinal plants. The aim of study was to evaluate anti-Candida activity of Z. multiflora against different species of Candida in vitro. Anti-Candida activity of the aqueous, ethanolic and methanolic maceration extract of the aerial parts of Z. multiflora Boiss was studied in vitro. Anti-Candida activity against Candida species was done using serial dilutions of extracts in Sabouraud's dextrose agar. Mi...

  12. Production and Purification of Anti-Rhombomys opimus Immunoglobulins

    Directory of Open Access Journals (Sweden)

    AA Akhavan

    2011-12-01

    Conclusion: HRP conjugated rabbit anti-Gerbil IgG has been produced by a few companies, but to our knowledge HRP conjugated rabbit anti-R. opimus Ig is not commercially available. Production of HRP conjugated rabbit anti-R. opimus Ig is considerably helpful for immunological studies of R. opimus, the main reservoir host of ZCL in Iran as well as some other countries.

  13. Syndrome in question: antisynthetase syndrome (anti-PL-7)*

    Science.gov (United States)

    Esposito, Ana Cláudia Cavalcante; Gige, Tatiana Cristina; Miot, Hélio Amante

    2016-01-01

    Antisynthetase syndrome is a rare autoimmune disease characterized by interstitial lung disease and/or inflammatory myositis, with positive antisynthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, ZO, OJ, anti-KE or KS). Other symptoms described include: non-erosive arthritis, fever, Raynaud's phenomenon, and "mechanic's hands." The first therapeutic option is corticotherapy, followed by other immunosuppressants. The prognosis of the disease is quite limited when compared to other inflammatory myopathies with negative antisynthetase antibodies. PMID:27828653

  14. Anti-inflammatory new coumarin from the Ammi majus L.

    Science.gov (United States)

    Selim, Yasser Abdelaal; Ouf, Nabil Hassan

    2012-01-12

    Investigation of the aerial parts of the Egyptian medicinal plant Ammi majus L. led to isolation of new coumarin, 6-hydroxy-7-methoxy-4 methyl coumarin (2) and 6-hydroxy-7-methoxy coumarin (3); this is the first time they have been isolated from this plant. The structures of the compounds (2 &3) were elucidated by spectroscopic data interpretation and showed anti-inflammatory and anti-viral activity. GRAPHICAL An efficient, one-new coumarin (2) was isolated from the aerial parts of the A. Majus L. was evaluated for their anti-viral and anti-inflammatory activities.

  15. Spin Symmetry for Anti-Lambda Spectrum in Atomic Nucleus

    Institute of Scientific and Technical Information of China (English)

    SONG Chun-Yan; YAO Jiang-Ming; MENG Jie

    2009-01-01

    The spin symmetry of the anti-Lambda spectrum in nucleus ~(16)O is studied in the relativistic mean field theory.The spin-orbit splittings of spin doublets are found to be around 0.03-0.07 MeV and the dominant components of the Dirac spinor for the anti-Lambda spin doublets are found to be near identical.It is indicated that there is an even better spin symmetry in the anti-Lambda spectrum than that in the anti-nucleon spectrum.

  16. Anti-DNA antibodies--quintessential biomarkers of SLE.

    Science.gov (United States)

    Pisetsky, David S

    2016-02-01

    Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

  17. Anti-D prophylaxis: past, present and future.

    Science.gov (United States)

    de Haas, M; Finning, K; Massey, E; Roberts, D J

    2014-02-01

    The new British Committee for Standards in Haematology (BCSH) guidelines for the use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the use of anti-D in ectopic pregnancy and after red cell salvage during caesarean section, of dosing with different preparations and distinguishing non-immune and immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus (Rh) D alloimmunisation during the third trimester is well established and requires careful and well-audited local implementation to achieve the maximum public health benefit. In the UK, such scrutiny may be provided by the reporting of failed anti-D prophylaxis at women who have produced an immune anti-D that is detectable for the first time in the current pregnancy through the voluntary Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD genotyping would avoid giving anti-D to RhD negative women carrying an RhD negative fetus. RAADP is directed by fetal RHD genotyping in some countries in Northern Europe led by the Netherlands and Denmark. The economic case for RAADP directed by fetal RHD genotyping needs to be carefully evaluated and in England is under consideration by National Institute for Health and Clinical Excellence (NICE). Possible future developments include the use of monoclonal anti-D preparations, now in advanced clinical trials, and also testing the hypothesis that directed RAADP from early in the second trimester may further reduce anti-D immunisation.

  18. Human rights orientation and modern anti-Semitism

    Directory of Open Access Journals (Sweden)

    Johannes Kopf-Beck

    2011-04-01

    Full Text Available The manifestations of anti-Semitism in Germany have changed since the end of WWII. Whereas in the past German anti-Semitism was overtly racist, today it is characterized more by subtle and latent facets. How are these modern facets, such as secondary anti-Semitism, latent anti-Semitism and anti-Semitic criticism of Israel, related to human rights orientations? A survey of experts and a pre-study provided the basis for developing the Human Rights Orientation Scale, which includes the four subscales of Endorsement, Application, Restriction and Willingness to engage in human rights activity. In a study of 304 German subjects, data was collected on human rights orientations and facets of modern anti-Semitism. The present paper introduces the questionnaire, discusses the relevance of the study for determining the relationships between human rights orientations and facets of modern anti-Semitism and summarizes the study's implications for viewing secondary anti-Semitism and prejudicial criticism of Israel as facets of modern anti-Semitism.

  19. Anti-Aliasing filter for reverse-time migration

    KAUST Repository

    Zhan, Ge

    2012-01-01

    We develop an anti-aliasing filter for reverse-time migration (RTM). It is similar to the traditional anti-aliasing filter used for Kirchhoff migration in that it low-pass filters the migration operator so that the dominant wavelength in the operator is greater than two times the trace sampling interval, except it is applied to both primary and multiple reflection events. Instead of applying this filter to the data in the traditional RTM operation, we apply the anti-aliasing filter to the generalized diffraction-stack migration operator. This gives the same migration image as computed by anti-aliased RTM. Download

  20. Spin Symmetry for Anti-Lambda Spectrum in atomic nucleus

    CERN Document Server

    Song, Chunyan; Meng, Jie

    2009-01-01

    The spin symmetry of anti-Lambda spectrum in nucleus ^{16}O has been studied in the relativistic mean field theory. The spin-orbit splittings of spin doublets are found to be around 0.03-0.07 MeV and the dominant components of the Dirac spinor for the anti-Lambda spin doublets are found to be near identical. It indicates that there is an even better spin symmetry in the anti-Lambda spectrum than that in the anti-nucleon spectrum.

  1. Frequent rhabdomyolysis in anti-NMDA receptor encephalitis.

    Science.gov (United States)

    Lim, Jung-Ah; Lee, Soon-Tae; Kim, Tae-Joon; Moon, Jangsup; Sunwoo, Jun-Sang; Byun, Jung-Ick; Jung, Keun-Hwa; Jung, Ki-Young; Chu, Kon; Lee, Sang Kun

    2016-09-15

    The aim of this study was to analyze the clinical presentation and provocation factors of rhabdomyolysis in anti-NMDAR encephalitis. Among the 16 patients with anti-NMDAR encephalitis in our institutional cohort, nine patients had elevated CK enzyme levels and clinical evidence of rhabdomyolysis. Rhabdomyolysis was more frequent after immunotherapy. The use of dopamine receptor blocker (DRB) increased the risk of rhabdomyolysis. None of the patients without rhabdomyolysis received DRBs. Rhabdomyolysis is a frequent complication in anti-NMDAR encephalitis and more common after immunotherapy and the use of DRBs increases the risk. Therefore, DRBs should be administered carefully in patients with anti-NMDAR encephalitis.

  2. Anti-NMDA Receptor Encephalitis in a Pregnant Woman.

    Science.gov (United States)

    Kim, Jiyoung; Park, Seung Ha; Jung, Yu Ri; Park, Soon Won; Jung, Dae Soo

    2015-06-01

    Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti-NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor encephalitis in a pregnant woman who presented with abnormal behavior, epileptic seizure, and hypoventilation.

  3. [Dynamic monitoring risk of anti-hepatoma new drug development].

    Science.gov (United States)

    Zhang, Jing; Fan, Wei; Li, Hong-Fa; Man, Shu-Li; Liu, Zhen; Gao, Wen-Yuan

    2014-10-01

    Risk monitoring of new Chinese patent anti-hepatoma drugs is tracking recognized risks and residual risks, identifying emerging risk and ensure the implementation of the plan, estimating the process of reducing effectiveness. The paper is mainly through understanding the status of Chinese patent anti-hepatoma drugs, the content, characteristic and analysis method of dynamic risk monitoring, and then select the risk control indicators, collect risk information. Finally, puts forward the thought of anti-hepatoma drugs listed evaluation in our country, and try to establish the model of dynamic risk management of anti-hepatoma drugs.

  4. Terrorism, Anti-Terrorism, and the Copycat Effect

    DEFF Research Database (Denmark)

    Jensen, Thomas

    that an increase in anti-terrorism makes it more likely that cells will plan small rather than large attacks. Furthermore, we see that an increase in anti-terrorism can make a terrorist attack more likely. Analyzing the problem of optimal anti-terrorism we see that the introduction of a copycat effect rationalizes...... an increase in the level of anti-terrorism after a large attack. Using this result we show how the copycat effect changes the dynamic pattern of terrorism attacks and what the long run consequences are...

  5. Anti-chloride permeability and anti-chloride corrodibility of a green high performance concrete admixture in concrete

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yongbao; LIU Xinrong; LIU Dongyan; CHEN Jiangong; HUANG Xiongjun

    2003-01-01

    The effects of green high performance concrete (GHPC) admixture on the anti-chloride permeability and anti- chloride corrodibility of concrete are studied by a series of experiments designed on the basis of the diffusion principle and electrochemical principle. The GHPC admixture consists of fly ash, gangue, slag, red mud, etc., of which the mass fraction of industrial residues is over 96 %. The anti-permeabilities and anti-corrodibilities of the tested GHPC and normal concrete (NC) are evaluated by the Diffusion Coefficients of chloride which was obtained by measuring the concentration of chloride in the tested systems by the voltage difference method. It is found that the adoption of GHPC admixture greatly improves the anti-chloride permeability and anti-chloride corrodibility by modifying the inner structure and contracting the porosity of concrete to the reduce considerably the diffusion rate of chloride. The admixture is desirable regarding its engineering performances as well as economical and environmental interests.

  6. PREPARATION OF ANTI-IDIOTYPIC ANTIBODIES SPECIFIC FOR ANTI-HEL AND ANALYSIS OF THEIR FUNCTIONAL MIMICRY

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. This study is to investigate the functional mimicry by using anti-idiotypic antibodies of enzymes.Results.Eight hybridomas strains secreting anti-idiotypic antibodies were selected and characterized. It was shown that two of eight anti-idiotypic antibodies secreted by two hybridomas(1A10C9 and 2A11 C1B3) could mimic HEL catalytic activity to lyse Micrococcus lysodeikticus and that the catalytic effect of mixed anti-idiotypic antibodies of 1A10C9 and 2A11C1B3 was stronger than that of one of them, but less than HEL.Conclusion. The results demonstrated that the anti-idiotypic antibodies that could mimic enzyme activity existed in the idiotype network during anti-enzymatic immune response.

  7. Anti-Aliased Rendering of Water Surface

    Institute of Scientific and Technical Information of China (English)

    Xue-Ying Qin; Eihachiro Nakamae; Wei Hua; Yasuo Nagai; Qun-Sheng Peng

    2004-01-01

    Water surface is one of the most important components of landscape scenes. When rendering spacious far from the viewpoint. This is because water surface consists of stochastic water waves which are usually modeled by periodic bump mapping. The incident rays on the water surface are actually scattered by the bumped waves,pattern, we estimate this solid angle of reflected rays and trace these rays. An image-based accelerating method is adopted so that the contribution of each reflected ray can be quickly obtained without elaborate intersection calculation. We also demonstrate anti-aliased shadows of sunlight and skylight on the water surface. Both the rendered images and animations show excellent effects on the water surface of a reservoir.

  8. [Hemorrhagic complications of anti-vitamin K].

    Science.gov (United States)

    Al-Hajje, A; Calop, N; Bosson, J L; Calop, J; Allenet, B

    2009-03-01

    Adverse events related to oral anticoagulants represent a major public health problem. Hemorrhagic episodes are the most frequent complications and can be life-threatening. A 10 month prospective survey on all cases treated with anti-vitamin K (AVK), and admitted to emergency room of CHU Grenoble, was conducted to identify the hemorrhagic adverse drug events (HADE). The evaluation support was a directive questionnaire and consisted of 3 parts: patient characteristics, patient's medicated treatment and the hemorrhagic event. 216 patients treated with AVK were identified and 68 of them presented a hemorrhagic adverse drug event. 60 patients older than 65 years out of 158, presented HADE (38%); versus 8 patients or = 5, 79% developed HADE versus 16% in the group who had their INR AVK were significant. Concerning missed dose, 48 patients declared taking the missed dose with the next dose or when they remembered: 35% of them developed HADE (p = 0.49).

  9. Anti-HIV diterpenes from Coleus forskohlii.

    Science.gov (United States)

    Bodiwala, Hardik S; Sabde, Sudeep; Mitra, Debashis; Bhutani, Kamlesh Kumar; Singh, Inder Pal

    2009-09-01

    Various extracts of the aerial parts of Coleus forskohlii (Labiatae) were prepared and evaluated at their non cytotoxic concentration against HIV-1 NL4-3. Chloroform, ethyl acetate and n-butanol extracts showed 45.6, 66.5 and 37.7% inhibition of HIV, respectively in CEM-GFP cells infected with HIV-1(NL4-3) at 5 microg/mL. Four diterpenes, 1-deoxyforskolin, 1,9-dideoxyforskolin, forskolin and isoforskolin were isolated from the chloroform extract and tested against the virus. Six semi-synthetic derivatives of forskolin have been prepared to study SAR. 1-Deoxyforskolin and forskolin were found to be active against HIV(NL4-3). This is first report of anti HIV activity of this plant and its isolated constituents.

  10. Anti-stiction coating for microelectromechanical devices

    Science.gov (United States)

    Hankins, Matthew G.; Mayer, Thomas M.; Wheeler, David R.

    2006-05-16

    A method for depositing an anti-stiction coating on a MEMS device comprises reacting the vapor of an amino-functionalized silane precursor with a silicon surface of the MEMS device in a vacuum chamber. The method can further comprise cleaning the silicon surface of the MEMS device to form a clean hydroxylated silicon surface prior to reacting the precursor vapor with the silicon surface. The amino-functionalized silane precursor comprises at least one silicon atom, at least one reactive amino (or imine) pendant, and at least one hydrophobic pendant. The amino-functionalized silane precursor is highly reactive with the silicon surface, thereby eliminating the need for a post-process anneal step and enabling the reaction to occur at low pressure. Such vapor-phase deposition of the amino-functionalized silane coating provides a uniform surface morphology and strong adhesion to the silicon surface.

  11. Anti-racist innovation and nurse education.

    Science.gov (United States)

    Cortis, J; Law, I G

    2005-04-01

    The focus on institutional racism within the Higher Education (HE) sector in the United Kingdom and nurse education, in particular, has so far been seriously lacking in investigation and scrutiny. The Race Relations (Amendment) Act (RRAA2000) has pushed institutional racism to the forefront of debates in public services, including both education and health services. This paper seeks to operationalise some key aspects of the debate over institutional racism and relates it to both these sectors. Based on empirical work funded by the Higher Education Funding Council for England and Wales (HEFCE) Innovations Project, this paper offers nurse education a framework to not only comply with the legal requirement of 'promoting racial harmony' (RRAA 2000) and the expectations from nursing as enshrined in the Code of Professional Conduct (NMC, 2000. The Code of Professional Conduct: Protecting the Public Through Professional Standards. NMC, London), but goes further to consider some key questions for anti-racist interventions.

  12. Anti-adhesive properties of fish tropomyosins

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Bernbom, Nete; Gram, Lone;

    2008-01-01

    Aims: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. Methods...... to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein...... the importance of substratum's physiochemical properties and exposure time with regards to protein adsorption/elution efficiency and subsequent bacterial adhesion. Significance and Impact of the Study: Fish tropomyosin-coatings could potentially offer a nontoxic and relatively inexpensive measure of reducing...

  13. Angiogenesis and Anti-Angiogenic Treatments

    Directory of Open Access Journals (Sweden)

    Ersin Demirer

    2013-10-01

    Full Text Available Blood vessels in our body is developed by vasculogenesis and angiogenesis. There have been new advances in molecular pathology and tumor biology areas in recent years. Angiogenesis is modulated by the balance between angiogenic and anti-angiogenic factors. Angiogenesis plays a key role in tumor growth. Drugs inhibiting angiogenesis have been in use in various malign or non-malign diseases. Inhibition of angiogenesis in malign diseases is a very attractive subject in medicine and studies are going on about long term affects and toxicities. Inhibition of angiogenesis is not an only treatment choice alone. It is a supplemental treatment option applied with conventional chemotherapy, radiotherapy, surgery, immunotherapy and hormonal therapy. It has been used in colorectal carcinoma, renal cell carcinoma, non-small cell lung cancer, glioblastoma, heoatocellular carcinoma, pancreatic neuroendocrine tumor, tyroid medullary cancer.

  14. Review of Anti-Inflammatory Herbal Medicines

    Directory of Open Access Journals (Sweden)

    Mona Ghasemian

    2016-01-01

    Full Text Available Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil’s claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.

  15. Human Rights and Cohen's Anti-Statism

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2014-01-01

    G. A. Cohen's critique of standard liberal interpretations of the difference principle has been very influential. According to Cohen, justice is not realized simply because the state's tax policies and other distributive tools maximize the position of the worst off. Rather - possibly in addition to......, but not to the exclusion of, certain state policies - justice requires talented people to improve the position of the worst off through their actions in their daily lives. Specifically, it prohibits talented people from insisting on inequality-causing incentives. To this extent, Cohen's view of distributive justice...... of human rights vulnerable to Cohenian criticisms parallel to those that he canvasses against the statist understanding of distributive justice? (2) If so, should we welcome an anti-statist understanding of human rights, or should we see it as a problem with Cohen's critique of a statist focus...

  16. Preparing Teachers for Anti-oppressive Education

    DEFF Research Database (Denmark)

    Baber, Sikunder Ali

    2004-01-01

    While theories and recommendations continue to proliferate in the educational research literature on what it means to teach towards social justice and to prepare teachers for such teaching, so do concerns that these theories and recommendations fail to account for the ways that the contexts...... of teaching cultural contexts, national contexts, political contexts always affect teaching in idiosyncratic, unpredictable and even contradictory ways. Given that much educational research fails to trouble the US-centric nature of prevailing conceptions of social justice and teacher education......, it is important to learn about the unique as well as shared challenges facing teacher educators around the globe. In this article, teacher educators from Asia, Africa, North America and South America offer a sampling of initiatives in anti-oppressive teacher education; that is, initiatives to prepare teachers...

  17. Analysis of "anti-crisis strategy" definition essence and its role in enterprise anti-crisis management

    Directory of Open Access Journals (Sweden)

    Тетяна Олександрівна Ставерська

    2016-12-01

    Full Text Available The analysis of existing research of the category essence of "anti-crisis strategy" is given, the main essential features are revealed. These features are best matching its content. Existing approaches to determine the definition of "anti-crisis strategy" are systematized and summarized. Based on the allocation of essential features of anti-crisis strategy, the author’s generalized definition of this category is formulated considering the trajectory of the turbulent processes in environment

  18. Resveratrol: Anti-Obesity Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Leixuri Aguirre

    2014-11-01

    Full Text Available Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule.

  19. Anti-diabetic and anti-cholesterolemic activity of methanol extracts of three species ofAmaranthus

    Institute of Scientific and Technical Information of China (English)

    Girija K; Lakshman K; Udaya Chandrika; Sabhya Sachi Ghosh; Divya T

    2011-01-01

    Objective:To investigate the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves ofAmaranthus caudatus,Amaranthus spinosus andAmaranthus viridis in normal and streptozotocin (STZ) induced diabetic rats.Methods:In this study, the anti-diabetic and anti-cholesterolemic activity of methanol extracts of leaves of all three plants was evaluated by using normal andSTZ induced diabetic rats at a dose of200 mg/kg and400 mg/kg p.o.daily for21days. Blood glucose levels and body weight were monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein and very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed.Results:It was found that all the three plants at 400 mg/kg dose showed significant anti-diabetic and anti-cholesterolemic activity (P<0.01), while at200 mg/kg dose less significant anti-diabetic activity (P<0.05) was observed.Conclusions:Methanol extracts ofAmaranthus caudatus,Amaranthus spinosus andAmaranthus viridis showed significant anti-diabetic and anti-cholesterolemic activity, which provides the scientific proof for their traditional claims.

  20. Mechanisms underlying the anti-aging and anti-tumor effects of lithocholic bile acid.

    Science.gov (United States)

    Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Mohtashami, Sadaf; Titorenko, Vladimir I

    2014-09-18

    Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  1. Anti-inflammatory and anti-nociceptive activity of the water decoction Desmodium gangeticum.

    Science.gov (United States)

    Rathi, Anshu; Rao, Ch V; Ravishankar, B; De, S; Mehrotra, S

    2004-12-01

    The water decoction of root and aerial parts of Desmodium gangeticum (Leguminosae) was examined for anti-inflammatory and anti-nociceptive activity in experimental animals. The root and aerial decoction in doses of 5, 10 and 20 mg /kg caused a dose-dependent inhibition of swelling caused by carrageenin equivalent to 14.58-51.02% protection and 14.43-38.67%, respectively, in cotton pellet granuloma. There was a significant increase in analgesio-meter-induced force equivalent to 6.56-67.66% protection and 22.18-73.83% protection in acetic acid-induced writhing. The result establishes the traditional use of water decoction of Desmodium gangeticum codified in Indian System of Medicine.

  2. Analgesic, anti-inflammatory and anti-pyretic activities of Thymus linearis.

    Science.gov (United States)

    Qadir, Muhammad Imran; Parveen, Amna; Abbas, Khizar; Ali, Muhammad

    2016-03-01

    The present study was aimed to investigate the antipyretic, analgesic and anti-inflammatory activity of aqueous methanolic and n-hexane extract of Thymus linearis. For measuring analgesic activity, writhing test, hot plate method and formalin test were performed and abdominal writhing was induced by intra-peritoneal injection of 0.2 ml of 3% acetic acid. While in formalin test, pain was experimentally induced by injecting 25 μl of 2.5% formalin in left hind paw. In hot plate method, pain was induced thermally by keeping the animals on a hot plate with temperature of about 51°C. Anti-inflammatory activity was assessed by carrageenan induced mice paw edema. For determination of antipyretic activity, pyrexia was induced by subcutaneous injection of 15% yeast. The results showed that both the extracts had significant analgesic activity (pThymus linearis may be used against pain, pyrexia and inflammation.

  3. Anti-cluster Decay and Anti-alpha Decay of Antimatter nuclei

    CERN Document Server

    Poenaru, D N; Greiner, W

    2015-01-01

    A broad extension of periodic system into the sector of antimatter could be possible sometimes in a remote future. We expect that anti-alpha spontaneous emission from an antimatter nucleus will have the same Q-value and half-life as alpha emission from the corresponding mirror nucleus. This is the consequence of the invariance of binding energy as well as of the surface and Coulomb energy when passing from matter to antimatter nuclei with the the same mass number and the same atomic number. The Q-values and half-lives of all measured up to now 27 cluster radioactivities are given together with Q-values and half-lives of the most important competitor --- $\\alpha$ decay. The lightest anti-alpha emitter, $^8\\bar{Be}$, will have a very short half-life of about $81.9\\cdot 10^{-18}$ s.

  4. Anti program death-1/anti program death-ligand 1 indigestive cancers

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Human tumors tend to activate the immune systemregulatory checkpoints as a means of escaping immunosurveillance.For instance, interaction between programdeath-1 (PD-1) and program death-ligand 1 (PD-L1) willlead the activated T cell to a state of anergy. PD-L1 isupregulated on a wide range of cancer cells. Anti-PD-1and anti-PD-L1 monoclonal antibodies (mAbs), calledimmune checkpoint inhibitors (ICIs), have consequentlybeen designed to restore T cell activity. Accumulatingdata are in favor of an association between PD-L1expression in tumors and response to treatment. APD-L1 expression is present in 30% to 50% of digestivecancers. Multiple anti-PD-1 (nivolumab, pembrolizumab)and anti-PD-L1 mAbs (MPDL3280A, Medi4736) areunder evaluation in digestive cancers. Preliminaryresults in metastatic gastric cancer with pembrolizumabare highly promising and phase Ⅱ will start soon. Inmetastatic colorectal cancer (CRC), a phase Ⅲ trialof MPDL3280A as maintenance therapy will shortlybe initiated. Trials are also ongoing in metastatic CRCwith high immune T cell infiltration (i.e. , microsatelliteinstability). Major challenges are ahead in order todetermine how, when and for which patients we shoulduse these ICIs. New radiologic criteria to evaluate tumorresponse to ICIs are awaiting prospective validation.The optimal therapeutic sequence and association withcytotoxic chemotherapy needs to be established. Finally,biomarker identification will be crucial to selection of patients likely to benefit from ICIs.

  5. Squalamine analogues as potential anti-trypanosomal and anti-leishmanial compounds.

    Science.gov (United States)

    Khabnadideh, S; Tan, C L; Croft, S L; Kendrick, H; Yardley, V; Gilbert, I H

    2000-06-05

    This paper concerns the synthesis of various simplified analogues of the novel anti-microbial agent, squalamine. The compounds were then investigated for activity against Trypanosoma brucei, the causative agent of African trypanosomiasis, Trypanosoma cruzi, the causative agent of Chagas disease and Leishmania donovani, the causative agent of visceral leishmaniasis. Several compounds showed in vitro activity, especially against T. brucei and L. donovani. However, one compound showed poor in vivo activity.

  6. Anti-reflective and anti-soiling coatings with self-cleaning properties

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Vinod; Brophy, Brenor L.

    2016-10-04

    Disclosed herein is a coated glass element including a glass component and a coating adhered to the glass component through siloxane linkages, the coating having at least one of an anti-reflective property, a high abrasion resistance property and a hydrophobic property, wherein the coating comprises a dried gel formed from at least one hydrolyzed alkoxysilane-based sol and at least one hydrolyzed organosilane-based sol.

  7. A review of anti-infective and anti-inflammatory chalcones.

    Science.gov (United States)

    Nowakowska, Zdzisława

    2007-02-01

    Chalcones, considered as the precursors of flavonoids and isoflavonoids, are abundant in edible plants, and have also been shown to display a diverse array of pharmacological activities. The purpose of this review is to provide an overview of the pharmacological activity of synthetic and naturally occurring chalcones. This review is complementary to earlier reviews and covers more recent reports of antimicrobial activity of chalcones (antibacterial and antifungal), as well as antileishmanial, antimalarial, antiviral and anti-inflammatory activities of these compounds.

  8. Biodegradable nanoassemblies of piperlongumine display enhanced anti-angiogenesis and anti-tumor activities

    Science.gov (United States)

    Liu, Yuanyuan; Chang, Ying; Yang, Chao; Sang, Zitai; Yang, Tao; Ang, Wei; Ye, Weiwei; Wei, Yuquan; Gong, Changyang; Luo, Youfu

    2014-03-01

    Piperlongumine (PL) shows an inhibitory effect on tumor growth; however, lipophilicity has restricted its further applications. Nanotechnology provides an effective method to overcome the poor water solubility of lipophilic drugs. Polymeric micelles with small particle size can passively target tumors by the enhanced permeability and retention (EPR) effect, thus improving their anti-tumor effects. In this study, to improve the water solubility and anti-tumor activity of PL, PL encapsulated polymeric micelles (PL micelles) were prepared by a solid dispersion method. The prepared PL micelles showed a small particle size and high encapsulation efficiency, which could be lyophilized into powder, and the re-dissolved PL micelles are homogenous and stable in water. In addition, a sustained release behavior of PL micelles was observed in vitro. Encapsulation of PL into polymeric micelles could increase the cytotoxicity, cellular uptake, reactive oxygen species (ROS) and oxidized glutathione (GSSG), and reduce glutathione (GSH) levels in vitro. Encapsulation of PL into polymeric micelles enhanced its inhibitory effect on neovascularization both in vitro and in vivo. Compared with free PL, PL micelles showed a stronger inhibitory effect on the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). Additionally, in a transgenic zebrafish model, embryonic angiogenesis was inhibited by PL micelles. Furthermore, PL micelles were more effective in inhibiting tumor growth and prolonging survival in a subcutaneous CT-26 murine tumor model in vivo. Therefore, our data revealed that the encapsulation of PL into biodegradable polymeric micelles enhanced its anti-angiogenesis and anti-tumor activities both in vitro and in vivo.

  9. Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Hossein Kazemian

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Chamomile ( Chamaemelum nobile is widely used throughout the world, and has anti-inflammatory, deodorant, bacteriostatic, antimicrobial, carminative, sedative, antiseptic, anti-catarrhal, and spasmolytic properties. Because of the increasing incidence of drug-resistant bacteria, the development of natural antibacterial sources such as medical herbs for the treatment of infectious diseases is necessary. Extracts from different plant parts such as the leaves, flowers, fruit, and bark of Combretum albiflorum, Laurus nobilis , and Sonchus oleraceus were found to possess anti-quorum sensing (QS activities. In this study, we evaluated the effect of C. nobile against Pseudomonas aeruginosa biofilm formationMETHODS:The P. aeruginosa samples were isolated from patients with different types of infection, including wound infection, septicemia, and urinary tract infection. The flowers of C. nobile were dried and the extract was removed using a rotary device and then dissolved in dimethyl sulfoxide at pH 7.4. The microdilution method was used to evaluate the minimum inhibitory concentration (MIC of this extract on P. aeruginosa , and biofilm inhibition was assayed.RESULTS:Eighty percent of the isolated samples (16/20 could form a biofilm, and most of these were isolated from wound infections. The biofilm inhibitory concentration of the C. nobile extract was 6.25-25mg/ml, whereas the MIC was 12.5-50mg/ml.CONCLUSIONS:The anti-QS property of C. nobile may play an important role in its antibacterial activity, thus offering an additional strategy in the fight against bacterial infections. However, molecular investigation is required to explore the exact mechanisms of the antibacterial action and functions of this phytocompound.

  10. Anti-inflammatory, anti-bacterial, and cytotoxic activity of fibrous clays.

    Science.gov (United States)

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio-; Ramírez-Apan, María Teresa; Gómez-Vidales, Virginia; Palacios, Eduardo; Montoya, Ascención; Ronquillo de Jesús, Elba

    2015-05-01

    Produced worldwide at 1.2m tons per year, fibrous clays are used in the production of pet litter, animal feed stuff to roof parcels, construction and rheological additives, and other applications needing to replace long-fiber length asbestos. To the authors' knowledge, however, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the anti-inflammatory, anti-bacterial, and cytotoxic activity by sepiolite (Vallecas, Spain) and palygorskite (Torrejon El Rubio, Spain). The anti-inflammatory activity was determined using the 12-O-tetradecanoylphorbol-13-acetate (TPA) and myeloperoxidase (MPO) methods. Histological cuts were obtained for quantifying leukocytes found in the epidermis. Palygorkite and sepiolite caused edema inhibition and migration of neutrophils ca. 68.64 and 45.54%, and 80 and 65%, respectively. Fibrous clays yielded high rates of infiltration, explained by cleavage of polysomes and exposure of silanol groups. Also, fibrous clays showed high inhibition of myeloperoxidase contents shortly after exposure, but decreased sharply afterwards. In contrast, tubular clays caused an increasing inhibition of myeloperoxidase with time. Thus, clay structure restricted the kinetics and mechanism of myeloperoxidase inhibition. Fibrous clays were screened in vitro against human cancer cell lines. Cytotoxicity was determined using the protein-binding dye sulforhodamine B (SRB). Exposing cancer human cells to sepiolite or palygorskite showed growth inhibition varying with cell line. This study shows that fibrous clays served as an effective anti-inflammatory, limited by chemical transfer and cellular-level signals responding exclusively to an early exposure to clay, and cell viability decreasing significantly only after exposure to high concentrations of sepiolite.

  11. Evaluation of the anti-inflammatory and anti-arthritic effects of some plant extracts

    OpenAIRE

    2011-01-01

    The objective of the present research was to study the anti-inflammatory activity of sweet basil flowers, leaves of eucalyptus and the aerial parts of celery and sage on acute inflammation along with the effect of a methanol extract of celery, sage and eucalyptus on adjuvant induced arthritis in rats. The effect of the methanol extract of celery, sage and eucalyptus on certain biochemical parameters in adjuvant arthritis and its safety in liver and kidney functions were evaluated. The fatty a...

  12. Anti-angiogenic and anti-inflammatory properties of kahweol, a coffee diterpene.

    Directory of Open Access Journals (Sweden)

    Casimiro Cárdenas

    Full Text Available BACKGROUND: Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules. METHODOLOGY/PRINCIPAL FINDINGS: The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish, the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells. CONCLUSION/SIGNIFICANCE: Taken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers.

  13. Anti-Angiogenic and Anti-Inflammatory Properties of Kahweol, a Coffee Diterpene

    Science.gov (United States)

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel A.

    2011-01-01

    Background Epidemiological studies have shown that unfiltered coffee consumption is associated with a low incidence of cancer. This study aims to identify the effects of kahweol, an antioxidant diterpene contained in unfiltered coffee, on angiogenesis and key inflammatory molecules. Methodology/Principal Findings The experimental procedures included in vivo angiogenesis assays (both the chicken and quail choriallantoic membrane assay and the angiogenesis assay with fluorescent zebrafish), the ex vivo mouse aortic ring assay and the in vitro analysis of the effects of treatment of human endothelial cells with kahweol in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Additionally, two inflammation markers were determined, namely, the expression levels of cyclooxygenase 2 and the levels of secreted monocyte chemoattractant protein-1. We show for the first time that kahweol is an anti-angiogenic compound with inhibitory effects in two in vivo and one ex vivo angiogenesis models, with effects on specific steps of the angiogenic process: endothelial cell proliferation, migration, invasion and tube formation on Matrigel. We also demonstrate the inhibitory effect of kahweol on the endothelial cell potential to remodel extracellular matrix by targeting two key molecules involved in the process, MMP-2 and uPA. Finally, the anti-inflammatory potential of this compound is demonstrated by its inhibition of both COX-2 expression and MCP-1 secretion in endothelial cells. Conclusion/Significance Taken together, our data indicate that, indeed, kahweol behaves as an anti-inflammatory and anti-angiogenic compound with potential use in antitumoral therapies. These data may contribute to the explanation of the reported antitumoral effects of kahweol, including the recent epidemiological meta-analysis showing that drinking coffee could decrease the risk of certain cancers. PMID:21858104

  14. Anti-allergic and anti-microbial activities of some Thai crops

    Directory of Open Access Journals (Sweden)

    Supinya Tewtrakul

    2008-07-01

    Full Text Available Thirteen Thai crops including banana, okra, jackfruit, germinated rice, rambutan, durian, jampadah, huasa potato,tamarind, coconut, mango, fan palm fruit and dioscorea tuber were tested for anti-allergic effect using RBL-2H3 cells andanti-microbial activity. These 13 crops, some of which included different parts, e.g. skin, flesh, and seed, were extracted withfour solvents separately [(95% ethanol (EtOH, 50% EtOH, water (W and hot water (HW], respectively, to obtain 112extracts. Among these extracts, mango seed in 50% EtOH possessed the highest anti-allergic activity against antigen-inducedb-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with an IC50 value of 7.5±0.8 mg/ml, followed bybanana (W, IC50 = 13.5±2.4 mg/ml, okra (W, IC50 = 13.6±3.1 mg/ml, jampadah skin (HW, IC50 = 13.8±3.9 mg/ml, tamarindseed coat (HW, IC50 = 14.2±3.1 mg/ml, jampadah flesh (W, IC50 = 14.6±3.1 mg/ml; whereas other crops possessed IC50values from 21.5->100 mg/ml. Moreover, the plants showing high anti-allergic effects were also possessed marked antibacterialactivity. Rambutan peel, mango peel, mango seed and tamarind seed coat exhibited appropriate anti-bacterialactivity against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa with MIC values ranging from 250-2,000 mg/ml, but did not show any effect towards Escherichia coli and Candida albicans. This study indicates that these Thaicrops may have potential as functional foods and neutraceuticals for treatment of allergy, allergy-related diseases and somebacterial infections.

  15. Anti-HIV-1 integrase and anti-allergic activities of Bauhinia strychnifolia

    Directory of Open Access Journals (Sweden)

    Kingkan Bunluepuech

    2013-12-01

    Full Text Available A stem ethanol extract of Bauhinia strychnifolia and its compounds were investigated for their anti-HIV-1 integrase (IN and anti-allergic activities. From bioassay-guided isolation, five compounds including quercetin (1, 3,5,7,3',5' pentahydroxyflavanonol-3-O-α-L-rhamnopyranoside (2, 3,5,7-trihydroxychromone-3-α-L-rhamnopyranoside (3 and a mixture of β-sitosterol (4 and stigmasterol (5 were isolated. Of the tested samples, compound 1 (quercetin showed the highest activity against HIV-1 IN with an IC50 value of 15.2 µM, followed by 3 (3,5,7-trihydroxychromone-3-α-L-rhamnopyranoside, 4+5 (mixture of β-sitosterol and stigmasterol and 2 (3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-L-rhamnopyranoside with % inhibition of 28.2, 26.2 and 6.7 at 100 µM, respectively. With regard to anti-allergic activity, quercetin (1 possessed the highest anti-allergic activity with an IC50 of 8.1 µM, followed by 3 (3,5,7-trihydroxychromone-3-α-L-rhamnopyranoside and 4+5 (mixture of β-sitosterol and stigmasterol with IC50 values of 52.1 and 77.5 µM, respectively. Whereas compound 2 (3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-L-rhamnopyranoside was inactive. The present study is the first report of chemical constituents and biological activities of Bauhinia strychnifolia.

  16. Evaluation of anti-nociceptive and anti-inflammatory activities of a heterofucan from Dictyota menstrualis.

    Science.gov (United States)

    Albuquerque, Ivan Rui Lopes; Cordeiro, Sara Lima; Gomes, Dayanne Lopes; Dreyfuss, Juliana Luporini; Filgueira, Luciana Guimarães Alves; Leite, Edda Lisboa; Nader, Helena Bonciani; Rocha, Hugo Alexandre Oliveira

    2013-08-02

    Fucan is a term that defines a family of homo- and hetero-polysaccharides containing sulfated l-fucose in its structure. In this work, a heterofucan (F2.0v) from the seaweed, Dictyota menstrualis, was evaluated as an antinociceptive and anti-inflammatory agent. F2.0v (20.0 mg/kg) inhibits 100% of leukocyte migration into the peritoneal cavity after chemical stimulation. However, F2.0v does not alter the expression of interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), as well as tumor necrosis factor alpha (TNF-α). F2.0v (20.0 mg/kg) has peripheral antinociceptive activity with potency similar to dipyrone. On the other hand, it had no effect on pain response on the hot plate test. Confocal microscopy analysis and flow cytometry showed that F2.0v binds to the surface of leucocytes, which leads us to suggest that the mechanism of action of anti-inflammatory and antinociceptive F2.0v is related to its ability to inhibit the migration of leukocytes to the site of tissue injury. In summary, the data show that F2.0v compound has great potential as an antinociceptive and anti-inflammatory, and future studies will be performed to further characterize the mechanism of action of F2.0v.

  17. Antioxidant, Anti-Glycation and Anti-Inflammatory Activities of Phenolic Constituents from Cordia sinensis

    Directory of Open Access Journals (Sweden)

    Muhammad Nasir

    2011-12-01

    Full Text Available Nine compounds have been isolated from the ethyl acetate soluble fraction of C. sinensis, namely protocatechuic acid (1, trans-caffeic acid (2, methyl rosmarinate (3, rosmarinic acid (4, kaempferide-3-O-β-D-glucopyranoside (5, kaempferol-3-O-β-D-glucopyranoside (6, quercetin-3-O-β-D-glucopyranoside (7, kaempferide-3-O-α-L-rhamnopyranosyl (1→6-β-D-glucopyranoside (8 and kaempferol-3-O-α-L-rhamno-pyranosyl (1→6-β-D-glucopyranoside (9, all reported for the first time from this species. The structures of these compounds were deduced on the basis of spectroscopic studies, including 1D and 2D NMR techniques. Compounds 1–9 were investigated for biological activity and showed significant anti-inflammatory activity in the carrageen induced rat paw edema test. The antioxidant activities of isolated compounds 1–9 were evaluated by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7–9 exhibited marked scavenging activity compared to the standard BHA. These compounds were further studied for their anti-glycation properties and some compounds showed significant anti-glycation inhibitory activity. The purity of compounds 2–5, 8 and 9 was confirmed by HPLC. The implications of these results for the chemotaxonomic studies of the genus Cordia have also been discussed.

  18. Evaluating the Anti-nociceptive and Anti-inflammatory Effects of Ketotifen and Fexofenadine in Rats

    Directory of Open Access Journals (Sweden)

    Mahdieh Anoush

    2015-06-01

    Full Text Available Purpose: As H1 and H3 receptors’ roles has been defined in peripheral pains in some papers and because histamine is known for its role in inflammatory responses; this study investigated the possible analgesic and anti-inflammatory effects of ketotifen and fexofenadine as relatively safe long acting anti histamines in both chronic chemical pain and acute inflammation in rats. Methods: In this study, male Sprague-Dawley rats weighing 225-250 grams were used. In order to evaluate the chemical chronic pain, sub-plantar injection of formalin applied and the pain scores were recorded every 15 seconds during 60 minutes. Carrageenan injection to the right hind paw was used for induction of acute inflammation and the paw edema was measured every 60 minutes for 4 hours. Results: Based on the results, both ketotifen and fexofenadine were able to significantly diminish chemical acute and chronic pain as well as inflammation in comparison with the control group and the effects were acceptable according to the standard treatment. Both effects for fexofenadine started later than those of ketotifen. Conclusion: According to the outcomes of the study, ketotifen and fexofenadine demonstrated significant analgesic and anti-inflammatory characteristics in both models of chemical pain and acute inflammation in laboratory animals.

  19. Anti-inflammatory and anti-oxidative activities of polyacetylene from Dendropanax dentiger.

    Science.gov (United States)

    Chien, Shih-Chang; Tseng, Yen-Hsueh; Hsu, Wei-Ning; Chu, Fang-Hua; Chang, Shang-Tzen; Kuo, Yueh-Hsiung; Wang, Sheng-Yang

    2014-11-01

    Dendropanax dentiger has been used as a folk medicine since ancient times. In our current study, we observed that D. dentiger exhibited a significant anti-inflammatory activity, which could efficiently inhibit nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced macrophage inflammation assay. (9Z,16S)-16-Hydroxy-9,17-octadecadiene-12,14-diynoic acid (HODA) was isolated from the leaves of D. dentiger following a bioactivity guided fractionation protocol. Our data indicated that HODA significantly inhibited the NO production in LPS-induced RAW 264.7 murine macrophage cells (IC50 = 4.28 μM). Consistent with these observations, the mRNA and protein expression levels of iNOS were also inhibited by HODA in a dose-dependent manner. HODA also reduced the translocation of NF-κB into nuclear fractions. Meanwhile, HODA enhanced Nrf-2 activation and its downstream antioxidant gene HO-1. We concluded that HODA possessed significant anti-inflammatory and anti-oxidative activity; the compound may have a potential for development as a chemoprevention agent.

  20. Syngeneic anti-idiotypic monoclonal antibodies to an anti-NeuGc-containing ganglioside monoclonal antibody.

    Science.gov (United States)

    Vázquez, A M; Pérez, A; Hernández, A M; Macías, A; Alfonso, M; Bombino, G; Pérez, R

    1998-12-01

    An IgM monoclonal antibody (MAb), named P3, has the characteristic to react specifically with a broad battery of N-glycolyl containing-gangliosides and with antigens expressed on breast tumors. When this MAb was administered alone in syngeneic mice, an specific IgG anti-idiotypic antibody (Ab2) response was induced, this Ab2 response was increased when P3 MAb was injected coupled to a carrier protein and in the presence of Freund's adjuvant. Spleen cells from these mice were used in somatic-cell hybridization experiments, using the murine myeloma cell line P3-X63-Ag8.653 as fusion partner. Five Ab2 MAbs specific to P3 MAb were selected. These IgG1 Ab2 MAbs were able to block the binding of P3 MAb to GM3(NeuGc) ganglioside and to a human breast carcinoma cell line. Cross-blocking experiments demonstrated that these Ab2 MAbs are recognizing the same or very close sites on the Abl MAb. The five Ab2 MAbs were injected into syngeneic mice and four of them produced strong anti-anti-idiotypic antibody (Ab3) response. While these Ab2 MAbs were unable to generate Ab3 antibodies with the same antigenic specificity than P3 MAb, three of them induced antibodies bearing P3 MAb idiotopes (Ag-Id+ Ab3). These results demonstrated that these Ab2 MAbs are not "internal image" antibodies, but they could define "regulatory idiotopes."