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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. 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...

  5. [{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.

  6. Dosimetry and microdosimetry of 188 Re-anti-CD20 and 131 I-anti-CD20 for the treatment of No Hodgkin lymphomas

    International Nuclear Information System (INIS)

    The purpose of this investigation was to prepare 131I-anti-CD20 and 188Re-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 131I-anti-CD20 and 188Re-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. 188Re-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 188Re-anti-CD20, 125I-anti-CD20 (positive control) and 188Re-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. 188Re-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 188Re-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 188Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or healthy organs. The absorbed dose (D) into cellular nucleus was calculated by two different

  7. 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

  8. Anti-CD20 multivalent HPMA copolymer-Fab′ conjugates for the direct induction of apoptosis

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    Chu, Te-Wei; Yang, Jiyuan; Kopeček, Jindřich

    2012-01-01

    A hybrid biomimetic system comprising high-molecular-weight, linear copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple Fab′ fragments of anti-CD20 monoclonal antibody (mAb) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by attachment of Fab′ fragments via thioether bonds. Exposure of human non-Hodgkin’s lymphoma (NHL) Raji B cells to the multivalent conjugates resulted in crosslinking of CD20 receptors and commenceme...

  9. 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

  10. Labelling and biological valuation of anti-CD-20 for treatment of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Full text: Anti-CD20 monoclonal chimeric humanized murine antibodies (Rituximab), have been successfully applied for the treatment of Non Hodgkin's Lymphoma. However, upon labelling of the mab-CD20 with β-emitters as 90Y, the therapeutic efficacy has significantly increased due to radiological effects of ionizing radiation. Our objective was to develop reliable and efficient methods for labelling anti-CD20 with β-emitters of therapeutic interest and simple and rugged quality control methods to evaluate radiochemical purity, biological performance and immunoreactivity assessment. 131I and 188Re have been used for the labelling of anti-CD20 as two attractive alternatives due to decay properties and availability (188Re: Eβmax: 2.2MeV, Eγ 0,155MeV, T=17h, generator produced; 131I: Eβmax: 0,63MeV, Eγ 0,364MeV, T=8d). Labelling of anti-CD20 was optimized following the oxidation procedure of chloramine-T in the case of 131I and the synthesis of 188Re(IV) complex with the previously reduced monoclonal antibody. Quality control of the species obtained were done by physicochemical methods, including ITLC-SG and HPLC, non specific protein precipitation, biological distribution in normal mice and immunoreactivity studies with membrane antigens extracted from isolated leucocytes. 131I- (more than 3.7 GBq/mL) was introduced on tyrosyl residues of the protein chain by adding 28 MBq to 20μg of anti CD20 (Mab Thera, 10mg/mL) at pH 7.4 and 1.3μg of Choramine-T. Purification was done by gel-permeation with sephadex G-25 (PD-10, Pharmacia). For labelling with 188Re, anti CD20 was first reduced by incubation with 2- mercaptoethanol and purified over a PD10 column. Fractions of reduced antibody were pooled and formulated as kit for instant labelling. Each kit contained 1mg anti-CD20; 82.8mg of sodium tartrate; 1.67 mg of stannous fluoride and 0.25 mg gentisic acid. For the labelling, sodium perrhenate (1.5-1.9 GBq) was acidified, added to the kit and then incubated for 1 hour at

  11. 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.)

  12. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: a case study.

    Science.gov (United States)

    Dorvignit, Denise; Palacios, Julio L; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casaco, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  13. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody

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    Dorvignit, Denise; Palacios, Julio L.; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casacó, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  14. Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L.

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    Bodogai, Monica; Lee Chang, Catalina; Wejksza, Katarzyna; Lai, Jinping; Merino, Maria; Wersto, Robert P; Gress, Ronald E; Chan, Andrew C; Hesdorffer, Charles; Biragyn, Arya

    2013-04-01

    The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo-targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20(Low) tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B-expressing cytolytic CD8(+) T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo. PMID:23365136

  15. Rituximab and Other New Anti-CD20 MAbs for Non-Hodgkin’s Lymphoma Treatment

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    Letizia Polito

    2013-10-01

    Full Text Available Non-Hodgkin’s lymphomas (NHLs are a heterogeneous group of different haematological cancers with a wide range of aggressiveness. NHLs represent >80% of lymphomas and the majority of NHLs involve B cells. CD20 represents a good target for NHL immunotherapy because it is largely expressed on B cell NHL and not on B cell precursors and plasma cells. The anti-CD20 monoclonal antibody (mAb rituximab (RTX was the first antibody approved by the FDA for lymphoma therapy and has revolutionised B cell lymphoma treatment. Several clinical trials have demonstrated the high efficacy of RTX, resulting in a significant improvement in overall response rates and in NHL patient survival. However, RTX, both as a single agent and in combination with chemotherapy, induces several side-effects and resistance mechanisms. Remarkable efforts have been made to improve RTX efficacy, including conjugation to an active moiety (radionuclide, toxin, enzyme, or drug and the development of new anti-CD20 mAbs. This review summarises the characteristics of RTX and other anti-CD20 mAbs for NHL treatment; the results of the main clinical trials are reported.

  16. Preparation of the radiopharmaceutical 131I-Anti-CD20 for the treatment of lymphomas

    International Nuclear Information System (INIS)

    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 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 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 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 CD20 highly expressed in

  17. 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

  18. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse.

    Science.gov (United States)

    Vincent, Marie; Teppaz, Géraldine; Lajoie, Laurie; Solé, Véronique; Bessard, Anne; Maillasson, Mike; Loisel, Séverine; Béchard, David; Clémenceau, Béatrice; Thibault, Gilles; Garrigue-Antar, Laure; Jacques, Yannick; Quéméner, Agnès

    2014-01-01

    Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. PMID:25072059

  19. 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

    the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre......-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...

  20. Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)

    Science.gov (United States)

    Tada, Minoru; Tatematsu, Ken-Ichiro; Ishii-Watabe, Akiko; Harazono, Akira; Takakura, Daisuke; Hashii, Noritaka; Sezutsu, Hideki; Kawasaki, Nana

    2015-01-01

    In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO− and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity. PMID:26261057

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  2. Labeling an anti-CD20 monoclonal antibody with 90Y

    International Nuclear Information System (INIS)

    Lymphomas are among the 10 leading causes of death, both in Cuba and in the world, with an increasing incidence in recent years. Follicular lymphoma low-grade (indolent) is one of the most common in the Western world, representing 1/3 of all non-Hodgkin lymphomas (NHL). More than 90% of patients present with disseminated disease at diagnosis and generally have a slow evolution and good response to conventional treatment; but radically changed its forecast to relapse, resistance to therapeutic and histologic transformation can occur. The monoclonal antibody therapy has been a promising therapeutic. In this respect CD20 antigen it has been considered one of the most attractive targets in the therapy of follicular B cell lymphoma This is expressed in more than 90% of cases, while not present in stem cells and lines progenitors. Despite the success of immunotherapy, the relapse rate is still considerable. In order to increase the cytotoxic potential of immunotherapy, marked with beta emitting radionuclides alpha particles or monoclonal antibodies are used today. Despite encouraging results in patients with non-Hodgkin lymphomas refractory to other treatments, the extremely high costs of these commercial radiopharmaceuticals have greatly limited its application, even in the first world. A sustainable alternative is the marking of other anti-CD20 monoclonal antibodies, so researchers from several countries have concentrated their efforts on rituximaby other similar antibodies labeled with therapeutic radionuclides, as a possible cost-effectively to more problem. Today in Cuba it has an electrolytic generator 90Sr-90Y Isotope Center, which ensures the availability of the radionuclide. In addition, the chimeric MAb rituximab is applied as part of the therapy of NHL in its health system and, recently, the Center for Molecular Immunology has obtained a chimeric monoclonal anti-CD20 antibody biosimilar rituximab, which is in phase clinical trial; which opens prospects for the

  3. 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.)

  4. 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

    . Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results...... of a retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty-five patients (median age 52 years, range 17-82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred...... of rituximab. The large majority of patients also received Pred and, in some cases, other concomitant immunosuppressive treatment during part of their rituximab treatment. A complete response (CR) was defined as a rise in the platelet count > 100 x 10(9)/L, a partial response (PR) as a rise in the platelet...

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

    OpenAIRE

    Roit, Fabio Da; Patrick J Engelberts; Taylor, Ronald P.; Breij, Esther C.W.; Gritti, Giuseppe; Rambaldi, Alessandro; Introna, Martino; Parren, Paul W H I; Beurskens, Frank J; Golay, Josée

    2015-01-01

    The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct ...

  6. 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.

    2015-01-01

    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. PMID:25994015

  7. 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. PMID:25994015

  8. Sequential Camouflage of the arachno-6,9-C2B8H14 Cage by Substituents.

    Science.gov (United States)

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Tok, Oleg L; Švec, Petr; Růžičková, Zdeňka; Růžička, Aleš

    2016-07-18

    Sequential methylation of arachno-6,9-C2B8H14 (1) led to a series of methyl derivatives and finally to the camouflaging of all boron positions by mixed persubstitution. Thus, deprotonation of 1 produced the [arachno-6,9-C2B8H13] anion (1(-)), the methylation of which with MeI in tetrahydrofuran proceeded on the open-face boron vertexes with the formation of 5-Me-arachno-6,9-C2B8H13 (2; yield 28%) and 5,8-Me2-arachno-6,9-C2B8H12 (3; yield 36%). Observed in this reaction was also a side formation of 2-Me-closo-1,6-C2B8H9 (4; yield 6%).The electrophilic AlCl3-catalyzed CH3(+) attack of the neutral 1 in neat MeI at ambient temperature afforded 1,3-Me2-arachno-6,9-C2B8H12 (5), while a 76-h heating at 120 °C generated a mixture of the di- and triiodo derivatives 1,2,3,4,8,10-Me6-5,7-I2-arachno-6,9-C2B8H6 (6) and 1,2,3,4,7-Me5-5,7,10-I3-arachno-6,9-C2B8H6 (7). On the other hand, a HOTf-catalyzed reaction between 1 and MeOTf at reflux resulted in the isolation of 2-TfO-1,3.4,5,7,8,10-Me7-arachno-6,9-C2B8H6 (8; Tf = CF3SO2; yield 65%). The compounds were characterized by multinuclear ((11)B, (1)H, (13)C, and (19)F) NMR spectroscopy, mass spectrometry, and elemental analysis, and the structures of compounds 1, 1(-), 5, and 6 were established by X-ray diffraction analysis. PMID:27351461

  9. Comparative studies of antibody anti-CD20 labeled with 188Re

    International Nuclear Information System (INIS)

    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 (99mTc) and rhenium-188 (188Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis (99mTc: T1/2 = 6 h, γ radiation = 140 keV) and therapy (188Re: T1/2 = 17 h, maximum β energy = 2.12 MeV) and to their availability in the form of 99Mo/99mTc and 188W/188Re 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 188Re using two techniques: the direct labeling method [188Re(V)] and the labeling method via the carbonyl nucleus [188Re(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 188Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99mTc and 188Re were employed through 2 different procedures: (1) labeling of intact RTX with 99mTc(I) and (2) reduced RTX (RTXred) labeled with 99mTc(I)/188Re(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 via carbonyl group, the results showed that the - SH groups of RTXred are a possible way of labeling. The formulation of 99m

  10. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: A case study

    OpenAIRE

    Dorvignit, Denise; Palacios, Julio L.; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casacó, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the ...

  11. 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

  12. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm-2 s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. 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 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  13. Multivalent system for therapy of non-Hod king lymphomas based on Anti-CD20 conjugated to gold nanoparticles

    International Nuclear Information System (INIS)

    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

  14. 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

  15. 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.

  16. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    Science.gov (United States)

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  17. 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.

  18. Potential therapeutic strategy for non-Hodgkin lymphoma by anti-CD20scFvFc/CD28/CD3zeta gene tranfected T cells

    Directory of Open Access Journals (Sweden)

    Zheng Yihu

    2010-09-01

    Full Text Available Abstract Background Anti-CD20 monoclonal antibody treatment has not only increased survival and cure rates in many non-Hodgkin lymphomas, but also has prompted an explosion in the development of novel antibodies and biologically active substances with specific cellular targets in the field of malignancies treatment. Since the robust immune responses are elicited by the gene-modified T cells, gene based T cell therapy may also provide a powerful tool for cancer immunotherapy. Methods In this study, we developed a vector construction encoding a chimeric T cell receptor that recognizes the CD20 antigen and delivers co-stimulatory signals to achieve T cell activation. One non-Hodgkin lymphoma cell line Raji cells co-cultured with peripheral blood-derived T cells were stably transfected with anti-CD20scFvFc/CD28/CD3zeta gene or anti-CD20scFvFc gene. T cells expressing anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene co-cultured with CD20 positive Raji cells for different times. Cell lysis assay was carried by [3H]TdR release assay. The expressions of Fas, Bcl-2 and Caspase-3 of Raji cells were detected by flow cytometric. The secretion of IFN-gamma and IL-2 in co-culture medium was tested by ELISA assay. Activity of AP-1 was analyzed by EMSA. Results Following efficient transduction of peripheral blood-derived T cells with anti-CD20scFvFc/CD28/CD3zeta gene, an obvious cell lysis of Raji cells was observed in co-culture. T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene had superior secretion of IFN-gamma and IL-2 compared to T cells transduced anti-CD20scFvFc gene. Also it led to a much stronger Fas-induced apoptosis signaling transduction in target cancer cells. Conclusion So adoptively T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene mediates enhanced anti-tumor activities against CD20 positive tumor cells, suggesting a potential of gene-based immunotherapy for non-Hodgkin lymphoma.

  19. Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells

    Science.gov (United States)

    Roscher, Mareike; Hormann, Inis; Leib, Oliver; Marx, Sebastian; Moreno, Josue; Miltner, Erich; Friesen, Claudia

    2013-01-01

    Radioimmunotherapy (RIT) is an emerging treatment option for non-Hodgkin lymphoma (NHL) producing higher overall response and complete remission rates compared with unlabelled antibodies. However, the majority of patients treated with conventional or myeloablative doses of radiolabelled antibodies relapse. The development of RIT with alpha-emitters is attractive for a variety of cancers because of the high linear energy transfer (LET) and short path length of alpha-radiation in human tissue, allowing higher tumour cell kill and lower toxicity to healthy tissues. In this study, we investigated the molecular effects of the alpha-emitter Bi-213 labelled to anti-CD20 antibodies ([Bi-213]anti-CD20) on cell cycle and cell death in sensitive and radio-/chemoresistant NHL cells. [Bi-213]anti-CD20 induced apoptosis, activated caspase-3, caspase-2 and caspase-9 and cleaved PARP specifically in CD20-expressing sensitive as well as in chemoresistant, beta-radiation resistant and gamma-radiation resistant NHL cells. CD20 negative cells were not affected by [Bi-213]anti-CD20 and unspecific antibodies labelled with Bi-213 could not kill NHL cells. Breaking radio-/chemoresistance in NHL cells using [Bi-213]anti-CD20 depends on caspase activation as demonstrated by complete inhibition of [Bi-213]anti-CD20-induced apoptosis with zVAD.fmk, a specific inhibitor of caspases activation. This suggests that deficient activation of caspases was reversed in radioresistant NHL cells using [Bi-213]anti-CD20. Activation of mitochondria, resulting in caspase-9 activation was restored and downregulation of Bcl-xL and XIAP, death-inhibiting proteins, was found after [Bi-213]anti-CD20 treatment in radio-/chemosensitive and radio-/chemoresistant NHL cells. [Bi-213]anti-CD20 seems to be a promising radioimmunoconjugate to improve therapeutic success by breaking radio- and chemoresistance selectively in CD20-expressing NHL cells via re-activating apoptotic pathways through reversing deficient

  20. 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

  1. 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...... CD20, thus depleting mature B cells in vivo. Methods We report the results of rituximab treatment in two patients with severe PV. In both patients, high-dose oral prednisolone and adjuvant therapy with intravenous immunoglobulins and mycophenolate mofetil failed to control disease activity....... Consequently, the patients were treated with two courses of four weekly intravenous infusions of rituximab (375 mg/m(2)) with a 6-month interval. Results Clinical improvement was already noticeable 3-6 weeks after the first infusion. After the second course, complete remission was achieved. Oral prednisolone...

  2. Dosimetric evaluation of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    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 188W/188Re generator system represents an attractive alternative radionuclide for therapy. 188Re is produced from beta decay of the 188W parent. In addition to the emission of high-energy electrons (Eβ= 2118 keV), 188Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of 188Re, the emission of gamma photon is an added advantage since the biodistribution of 188Re-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)

  3. 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.

  4. 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)

  5. Progress in anti-CD20 monoclonal antibodies and their clinical application%抗CD20单抗的研究进展及其临床应用

    Institute of Scientific and Technical Information of China (English)

    梁碧华; 樊翌明; 朱慧兰

    2011-01-01

    Anti-CD20 monoclonal antibodies have been applied to the treatment of many autoimmune diseases and severe urticaria with favourable outcomes. Current researches about anti-CD20 monoclonal antibodies are focused on their application in refractory urticaria such as autoimmune urticaria and urticarial vasculitis. Their mechanism of action has not been defined. B cell depletion mechanism is considered to be associated with complement-dependent cytotoxicity, antibody dependent cellular cytotoxicity, direct induction of apoptosis, etc. This paper outlines the progress in researches on anti-CD20 monoclonal antibodies and their application in autoimmune diseases and urticaria, in order to provide evidence for their use in urticaria, and to predict their perspectives in the treatment of refractory urticaria.%抗CD20单克隆抗体目前已用于治疗较多的自身免疫性疾病,并有研究将其用于严重荨麻疹的治疗,且取得良好疗效.但相关的研究主要局限在自身免疫性荨麻疹或荨麻疹性血管炎等难治性荨麻疹中的应用,其作用机制尚未明确.B细胞清除机制认为与补体依赖性细胞毒性反应、抗体依赖细胞介导的细胞毒作用及直接诱导B淋巴细胞凋亡等有关.概述抗CD20单克隆抗体目前的研究进展及其在自身免疫性疾病和荨麻疹中的临床应用,旨在进一步揭示其可用于荨麻疹治疗的证据,从而更好地了解其在难治性荨麻疹中应用的前景.

  6. Efficient inhibition of B-cell lymphoma xenografts with a novel recombinant fusion protein: anti-CD20Fab-LDM.

    Science.gov (United States)

    Xin, C; Ye, S; Ming, Y; Shenghua, Z; Qingfang, M; Hongxing, G; Xu, S; Yuanfu, X; Yuan, Z; Dongmei, F; Juanni, L; Yingdai, G; Lianfang, J; Rongguang, S; Zhenping, Z; Jianxiang, W; Tao, C; Chunzheng, Y; Dongsheng, X; Yongsu, Z

    2010-10-01

    Lidamycin (LDM) is a new member of enediyne antitumor antibiotics family that can be separated and reconstituted. It consists of a labile active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). LDM is now in phase II clinical trials. In this study, we described the antitumor features of a fusion protein of LDM, anti-CD20Fab-LDM, targeted to CD20 expressed by B-lymphoid malignancies. Especially, LDM was prepared by a novel two-step method including DNA recombination and molecular reconstitution. Anti-CD20Fab-LDM exerted potent cytotoxicity against CD20+ B-cell lymphoma cell lines in vitro (IC50: 10-30 pM) and in the Raji xenograft model. Two Raji xenografts were allowed to grow to an initial mass of 80 and 500 mm³, respectively, and then anti-CD20Fab-LDM was administered intravenously with the highest dose of 4 nmol kg⁻¹ . The inhibition rates of tumor growth were 90.1 and 85%, which were saliently superior to those of nontargeted LDM. It is noteworthy that anti-CD20Fab-LDM can inhibit the growth of patient-derived cells, including rituximab-resistant patient-derived cells. Thus, CD20-targeted delivery of LDM is a specific and potent therapeutic strategy for B-lymphoid malignancies. In addition, the two-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs. PMID:20463754

  7. Immunotherapy with the trifunctional anti-CD20 x anti-CD3 antibody FBTA05 (Lymphomun) in paediatric high-risk patients with recurrent CD20-positive B cell malignancies.

    Science.gov (United States)

    Schuster, Friedhelm R; Stanglmaier, Michael; Woessmann, Wilhelm; Winkler, Beate; Siepermann, Meinolf; Meisel, Roland; Schlegel, Paul G; Hess, Jürgen; Lindhofer, Horst; Borkhardt, Arndt; Buhmann, Raymund

    2015-04-01

    Children with B cell malignancies refractory to standard therapy are known to have a poor prognosis and very limited treatment options. Here, we report on the treatment and follow-up of ten patients diagnosed with relapsed or refractory mature B-cell Non Hodgkin Lymphoma (B-NHL), Burkitt leukaemia (B-AL) or pre B-acute lymphoblastic leukaemia (pre B-ALL). All children were treated with FBTA05 (now designated Lymphomun), an anti-CD3 x anti-CD20 trifunctional bispecific antibody (trAb) in compassionate use. Within individual treatment schedules, Lymphomun was applied (a) after allogeneic stem cell transplantation (allo-SCT, n = 6) to induce sustained long-term remission, or (b) stand alone prior to subsequent chemotherapy to eradicate residual disease before allo-SCT (n = 4). Nine of ten children displayed a clinical response: three stable diseases (SD), one partial remission (PR) and five induced or sustained complete remissions (CR). Five of these nine responders died during follow-up. The other patients still maintain CR with a current overall survival of 874-1424 days (median: 1150 days). In conclusion, despite the dismal clinical prognosis of children refractory to standard therapy, immunotherapy with Lymphomun resulted in a favourable clinical outcome in this cohort of refractory paediatric patients. PMID:25495919

  8. 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)

  9. Internal radiotherapy. 2. Treatment of non-hodgkin's lymphoma with 90Y-labeled anti-CD20 monoclonal antibody

    International Nuclear Information System (INIS)

    This paper describes recent trends of radioimmunotherapy using specific monoclonal antibodies against tumors, its principle and outcomes, with major emphasis on the title. When the antibodies like rituximab (rit), anti-CD20 antibody against B-cell malignant lymphoma, are labeled by a certain radioisotope, they become more active in specifically killing malignant cells by their immune cytotoxicity following binding plus lethal effect of radiation (beta ray). In Western areas, 90Y-labeled (ibritumomab, ibrit) or 131I-labeled rit is now available for the purpose. The efficacy of the former ibrit in the phase III trial has been reported to be 83%, in contrast to that of rit alone, 56%, with the similar safety to rit, in out-patients with the tumor. The protocol for the therapy is consisted from the first therapy with intravenous rit and imaging by 111In-labeled rit on day 1 and the second with the rit and ibrit (0.4 mCi/kg) on day 8. Patients are excluded from the latter therapy when the image by 111In shows the abnormal distribution in the liver and bone marrow. In Japan, phase I/II clinical trials of ibrit have been conducted to confirm its efficacy and safety and the agent is to be approved within this year. The radioimmunotherapy is thought to become more popular. (T.I.)

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

    International Nuclear Information System (INIS)

    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 177Lu, 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 177Lu-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 177LuCl3 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)

  11. Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in Peritoneum of Balb/c Mice

    OpenAIRE

    Leili Aghebati; Jalal Abdolalizadeh; Jafar Majidi; Behzad Baradaran; Koushan Sineh Sepehr; Fatemeh Zare Shahneh

    2013-01-01

    Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously ...

  12. 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.

  13. 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.

  14. 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.

  15. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    Directory of Open Access Journals (Sweden)

    Sofia H L Frost

    Full Text Available 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.Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma or Granta (mantle cell lymphoma xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-biotin second step reagent.The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq as for 177Lu (0.6 Gy/MBq. More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma

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

    International Nuclear Information System (INIS)

    Purpose 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. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  17. Antitumor effects of an engineered and energized fusion protein consisting of an anti-CD20 scFv fragment and lidamycin.

    Science.gov (United States)

    Fang, Hong; Miao, Qingfang; Zhang, Shenghua; Cheng, Xin; Xiong, Dongsheng; Zhen, Yongsu

    2011-03-01

    Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other diseases. CD20 antigen, which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin's Lymphoma, is an attractive target for the therapy of B-lymphoid malignancies. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical trials. In this study, we prepared an engineered fusion protein, scFv-LDP, consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA recombination. After purification and refolding, scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining assays. The energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and scFv-LDP. MTT assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells, with IC(50) values of 1.21×10(-11) and 6.24×10(-11) mol L(-1), respectively. An in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also utilized. Drugs were given intravenously on day 14 and 21 after tumor transplantation. In terms of maximal tolerated doses, scFv-LDP-AE at 0.3 mg kg(-1) suppressed tumor growth by 79.3%, and LDM at 0.05 mg kg(-1) by 68.6% (P<0.05). Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy. PMID:21416325

  18. Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in Peritoneum of Balb/c Mice

    Directory of Open Access Journals (Sweden)

    Leili Aghebati

    2013-02-01

    Full Text Available Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. After twelve days, approximately 7 ml ascetic fluid was harvested from the peritoneum of each mouse. Evaluation of mAb titration was assessed by ELISA method. In the present study, we describe a protocol for large scale production of MAbs. Results: We prepared monoclonal antibodies (mAbs with high specificity and sensitivity against human CD20 by hybridoma method and characterized them by ELISA. The subclass of antibody was IgG2a and its light chain was kappa. Ascetic fluid was purified by Protein-A Sepharose affinity chromatography and the purified monoclonal antibody was conjugated with FITC and Immunofluorescence was done for confirming the specific binding. Conclusion: The conjugated monoclonal antibody could have application in diagnosis B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells.

  19. Transient B-Cell Depletion with Anti-CD20 in Combination with Proinsulin DNA Vaccine or Oral Insulin: Immunologic Effects and Efficacy in NOD Mice

    OpenAIRE

    Ghanashyam Sarikonda; Sowbarnika Sachithanantham; Yulia Manenkova; Tinalyn Kupfer; Amanda Posgai; Clive Wasserfall; Philip Bernstein; Laura Straub; Pagni, Philippe P.; Darius Schneider; Teresa Rodriguez Calvo; Marilyne Coulombe; Kevan Herold; Gill, Ronald G.; Mark Atkinson

    2013-01-01

    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 i...

  20. Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and immune thrombocytopenic purpura.

    Science.gov (United States)

    Milani, Cannon; Castillo, Jorge

    2009-04-01

    Veltuzumab is a humanized, second-generation anti-CD20 mAb currently under development by Immunomedics Inc for the potential treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Licensee Nycomed is developing veltuzumab for the potential treatment of rheumatoid arthritis and immune thrombocytopenic purpura (ITP). Veltuzumab contains 90 to 95% human antibody sequences with identical antigen framework regions to epratuzumab (a humanized anti-CD22 mAb) and similar antigen-binding determinants to rituximab (chimeric, anti-CD20 mAb and the first-line treatment of aggressive and indolent NHL). In vitro studies have demonstrated that veltuzumab has enhanced binding avidities and a stronger effect on complement-dependent cytotoxicity compared with rituximab in selected cell lines. In dose-finding phase I/II clinical trials in patients with low-grade NHL, intravenous veltuzumab demonstrated a substantial rate of complete responses in concurrence with shorter and more tolerable infusions compared with rituximab. Currently there has been no evidence of an immune response to repeated administrations, and no serious adverse events related to veltuzumab treatment in patients with NHL. Veltuzumab is undergoing clinical trials using a low-dose subcutaneous formulation in patients with NHL, CLL and ITP. Prospective, randomized clinical trials are needed to clarify the role veltuzumab will play in a market where the therapy of B-cell lymphoproliferative disorders is dominated by rituximab. PMID:19330725

  1. Influence of anti-CD20 monoclonal antibody combined with IL-10 on immune function of spleen in NOD mice%Anti-CD20与 IL-10联合应用对非肥胖型糖尿病小鼠脾脏免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    任安霞; 于淑凤; 张丽娟; 陈志红; 李堂

    2015-01-01

    Objective To observe the influence of anti-CD20 monoclonal antibody ( Anti-CD20 ) combined with inter-leukin 10 ( IL-10) on the immune function of spleen in non-obese diabetic ( NOD) mouse.Methods Twenty-four NOD mice were randomly divided into four groups , 6 mice in each group:groups A, B, C and D, which were caudal venously injected with 250μg Anti-CD20 , 250μg Anti-CD20 +0.1 mL IL-10, 0.1 mL IL-10 and 0.1 mL normal saline at day 1, 8, 15 and 21, respectively.All mice were sacrificed 12 weeks after first injection and the spleens were immediately taken out . The number of CD4+T cells, CD3+T cells and the levels of IL-10 and IL-27 were detected by immunohistochemistry . Results Compared with group D, the number of CD+4 T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues were increased in the groups A , B and C (all P<0.01).Compared with groups A and C , the number of CD4+T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues were increased in the group B (all P<0.01). Conclusion The combined administration of Anti-CD20 and IL-10 increases the number of CD+4 T cells, CD+3 T cells and the levels of IL-10 and IL-27 in the spleen tissues , and thus it regulates the immune microenvironment and prevents the oc-currence of diabetes .%目的:观察抗CD20单克隆抗体(Anti-CD20)与白细胞介素10(IL-10)联合应用对非肥胖型糖尿病(NOD)小鼠脾脏免疫功能的影响。方法将24只NOD小鼠随机分为A、B、C、D组各6只,分别于第1、8、15、21天尾静脉注射Anti-CD20250μg、Anti-CD20250μg +IL-100.1 mL、IL-100.1 mL和生理盐水0.1 mL。首次用药后第12周断颈处死小鼠,立即取出脾脏,采用免疫组化法检测脾脏组织中的CD4+、CD3+T细胞及IL-27、IL-10。结果与D组比较,A、B、C组脾脏组织中CD4+、CD3+T细胞数量及IL-27、IL-10表达增加( P均<0.01);与A、C组比较,B组脾脏组织中CD+4、CD+3 T

  2. 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.)

  3. 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.

  4. The study of labeling with Iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    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

  5. The study of labeling with iodine-131 of monoclonal antibody anti-CD20 used for the treatment of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    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 anti-CD20 (ex., 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, 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 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 combined with freeze appears more suitable and capable of minimizing autoradiolysis of the antibody labeled 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

  6. 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.

  7. Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Shahin Shamsian Bibi

    2008-09-01

    Full Text Available Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody.Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.

  8. 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.

  9. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities

  10. 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.

  11. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, B.; Lepretre, S.; Pedersen, L.M.;

    2008-01-01

    Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusio...

  12. Chimaeric anti-CD20 monoclonal antibody (rituximab) in post-transplant B-lymphoproliferative disorder following stem cell transplantation in children.

    Science.gov (United States)

    Faye, A; Quartier, P; Reguerre, Y; Lutz, P; Carret, A S; Dehée, A; Rohrlich, P; Peuchmaur, M; Matthieu-Boué, A; Fischer, A; Vilmer, E

    2001-10-01

    Post-transplant lymphoproliferative disorder (PTLD) after haemopoietic stem cell transplantation is a serious complication that occurs in 8-22% of patients with high-risk factors. We retrospectively investigated tolerance and efficacy of humanized anti-CD20 monoclonal antibody (rituximab) as first-line treatment in 12 children with B-cell PTLD. At diagnosis, eight patients had tumoral involvement. The other four patients had fever, associated with raised Epstein-Barr virus (EBV) viral load and monoclonal gammopathy. Rituximab was given at the dose of 375 mg/m2 once a week by intravenous infusion (1-9 infusions). Only 1/48 infusions was associated with a grade 2 clinical adverse event. Eight out of 12 (66%) patients responded to the treatment and were in complete remission. All patients without tumoral involvement responded to the treatment. A rapid decrease in fever within 1 week was observed in all responders. Non-responders did not show any clinical response during the first week. Tumoral involvement and immunodepression seemed to be more marked in non-responders. Rituximab was an effective and well-tolerated treatment of B-cell PTLD. Early treatment before tumoral involvement seemed to be the most effective approach. Lack of rapid response should lead to intensification of PTLD treatment. Pre-emptive treatment should be considered and evaluated in further longitudinal multicentre studies.

  13. CD20单克隆抗体治疗老年弥漫性B细胞淋巴瘤的研究%Study on the anti CD20 monoclonal antibody treatment of senile diffuse course B cel lymphoma

    Institute of Scientific and Technical Information of China (English)

    李玉巧; 梁志伟; 罗国桢

    2014-01-01

    目的:观察抗CD20单克隆抗体治疗老年弥漫性B细胞淋巴瘤的临床疗效。方法:将我院收治的老年B细胞淋巴瘤28例分为两组,一组为R-CHOP组15例,另一组为对照组CHOP组,4-6个疗程进行疗效评价。结果:RCHOP方案组总缓解率为73.3.%,对照组CHOP方案治疗总缓解率为46.2%,不良反应与对照组无明显增加。结论:抗CD20单克隆抗体联合化疗治疗老年B细胞淋巴瘤疗效好,不良反应少。%Objective:To observe the anti CD20 monoclonal antibody the clinical curative effect of the treatment of senile diffuse B cel lymphoma,Method:The aged B cel lymphoma in our hospital 28 cases were divided into two groups,A group of 15 patients in the R-CHOP group,Another group was control group CHOP group,To evaluate the curative effect of 4-6 Results: the RCHOP regimen group total remission rate was 73.3.%,The control group of CHOP regimen in the treatment of the total response rate was 46.2%,Adverse reactions and control group had no obvious increase.Conclusion: Anti CD20 monoclonal antibody combined with chemotherapy efficacy in the treatment of aged B cel lymphoma, less adverse reaction.

  14. 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

  15. 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

  16. 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

  17. 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 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. PMID:27334114

  18. 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.

  19. 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.

  20. 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

  1. 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.)

  2. Cloning of variable region and signal peptide genes of anti-CD20 monoclonal antibody by RLM-RACE%用RLM-RACE法克隆抗CD20单克隆抗体可变区基因及其信号肽基因

    Institute of Scientific and Technical Information of China (English)

    王玉刚; 冯健男; 沈倍奋

    2005-01-01

    目的:寻找一种可同时钓取抗CD20 mAb VL、 VH基因及其信号肽基因的方法.方法: 使用Trizol提取杂交瘤细胞1-28的总RNA, 分别采用传统的快速扩增5' cDNA末端 (traditional rapid amplification of 5' cDNA end, T-5' RACE)和RNA连接酶介导的快速扩增5' cDNA末端 (RNA ligase-mediated rapid amplification of 5' cDNA end, RLM-RACE) 的方法钓取目的基因.将其克隆到pGEM-T Easy载体上, 测序后, 与Kabat数据库和GenBank中相应的序列进行比对.结果: 采用RLM-RACE法可同时钓取到抗CD20 mAb VL、 VH基因及其信号肽基因, 而用T-5' RACE法仅能获得VL基因及其信号肽基因.结论: RLM-RACE法是钓取抗体V区基因和信号肽基因的好方法.

  3. 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.

  4. Perspectives of ofatumumab as CD20 targeted therapy in rheumatoid arthritis and other autoimmune diseases.

    Science.gov (United States)

    Pers, Yves Marie; Jorgensen, Christian

    2016-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed as a severe destructive disease. The treatment strategies include anti-CD20 monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20 antibodies including rituximab and ocrelizumab, and bind the epitope located on the large loop of CD20. This explains a more durable B-cell depletion and a different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and analyze the results in RA and other B-cell-mediated autoimmune diseases. The randomized trial in RA showed clinical efficacy comparable to rituximab at week 24. However, structural impact has not been demonstrated. Studies including RA patients refractory to rituximab would be useful to define the optimal strategy of ofatumumab therapy. PMID:27485081

  5. Statins impair antitumor effects of rituximab by inducing conformational changes of CD20.

    Directory of Open Access Journals (Sweden)

    Magdalena Winiarska

    2008-03-01

    Full Text Available BACKGROUND: Rituximab is used in the treatment of CD20+ B cell lymphomas and other B cell lymphoproliferative disorders. Its clinical efficacy might be further improved by combinations with other drugs such as statins that inhibit cholesterol synthesis and show promising antilymphoma effects. The objective of this study was to evaluate the influence of statins on rituximab-induced killing of B cell lymphomas. METHODS AND FINDINGS: Complement-dependent cytotoxicity (CDC was assessed by MTT and Alamar blue assays as well as trypan blue staining, and antibody-dependent cellular cytotoxicity (ADCC was assessed by a 51Cr release assay. Statins were found to significantly decrease rituximab-mediated CDC and ADCC of B cell lymphoma cells. Incubation of B cell lymphoma cells with statins decreased CD20 immunostaining in flow cytometry studies but did not affect total cellular levels of CD20 as measured with RT-PCR and Western blotting. Similar effects are exerted by other cholesterol-depleting agents (methyl-beta-cyclodextrin and berberine, but not filipin III, indicating that the presence of plasma membrane cholesterol and not lipid rafts is required for rituximab-mediated CDC. Immunofluorescence microscopy using double staining with monoclonal antibodies (mAbs directed against a conformational epitope and a linear cytoplasmic epitope revealed that CD20 is present in the plasma membrane in comparable amounts in control and statin-treated cells. Atomic force microscopy and limited proteolysis indicated that statins, through cholesterol depletion, induce conformational changes in CD20 that result in impaired binding of anti-CD20 mAb. An in vivo reduction of cholesterol induced by short-term treatment of five patients with hypercholesterolemia with atorvastatin resulted in reduced anti-CD20 binding to freshly isolated B cells. CONCLUSIONS: Statins were shown to interfere with both detection of CD20 and antilymphoma activity of rituximab. These studies

  6. 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.

  7. 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 ...

  8. 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.

  9. Novel CD20 monoclonal antibodies for lymphoma therapy

    Directory of Open Access Journals (Sweden)

    Cang Shundong

    2012-10-01

    Full Text Available Abstract Rituximab (RTX, a monoclonal antibody (mAb against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin’s lymphoma (NHL. Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106, ocrelizumab (PRO70769, and third-generation mAbs, AME-133v (ocaratuzumab, PRO131921 and GA101 (obinutumumab.

  10. 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.

  11. 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 with r...

  12. 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

  13. CD20 antibody primes B lymphocytes for type I interferon production.

    Directory of Open Access Journals (Sweden)

    Dongsheng Xu

    Full Text Available CD20 is a B cell surface marker that is expressed in various stages in B lymphocytes and certain lymphomas. Clinical administration of CD20 antibody, such as rituximab, is used widely to treat human B-cell lymphomas and other diseases. However, CD20 antibody failed to treat systemic lupus erythematosus (SLE or lupus. The reason for the failure is currently unknown. Type I interferons (IFN are a major component for the host innate immunity, and a key pathogenic factor in lupus. We found that CD20 antibody potentiated human B cells for its production of IFNs in vitro. This function was specific to CD20-expressing cells and the potentiation function seems to be instant. In addition, ectopic expression of CD20 in non-B-lymphocytes increased the IFN promoter reporter activities. Because IFNs are a key pathogenic factor in lupus, our data suggest that, in the presence of virus infection, the CD20-antibody-mediated enhancement of IFN production might be related to its failure in lupus treatments. This work may provide new insights for CD20-Ab therapeutic applications.

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

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with [67Ga]-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 CH2Cl2. 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 67Ga-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 μm filter. Preliminary biodistribution studies in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28 h. (orig.)

  16. Development of [64Cu]-DOTA-anti-CD20 for targeted therapy

    International Nuclear Information System (INIS)

    Copper-64 was produced as a by-product of 55Co via 64Ni(p,n)64Cu by 15 MeV proton bombardment of natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [64Cu]-CuCl2. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA and N-hydroxy succinimide (NHS) in CH2Cl2 followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 deg C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90-95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic 64Cu- DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 deg C. (author)

  17. CD20 expression characteristic and prognosis in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    夏敏

    2014-01-01

    Objective To analyzed the expression and clinical characteristics of CD20 marker in children with B-lineage acute lymphoblastic leukemia(B-ALL)and evaluated its medical significance in assessing the prognosis of disease.Methods From November 2008 to July 2012,125cases of children with B-lineage acute lymphoblastic leukemia were collected from Shanghai Children’s Hospital,

  18. The Role of CD16+, CD56+, NK (CD16+/CD56+ and B CD20+ Cells in the Outcome of Pregnancy in Women with Recurrent Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Mehri Ghafourian

    2015-01-01

    Full Text Available Objectives: Recurrent Spontaneous Abortion (RSA is the most common complication of pregnancy. It is considered as one of the most important issues of reproduction in the world. RSA is defined as having three or more miscarriages in the first trimester of pregnancy. Increase in peripheral blood lymphocytes may be associated with abortion; therefore,the study was aimed to investigate and compare the peripheral blood CD16+, CD56+, NK(CD16+/CD56+ and B CD20+ cells populations in diagnosis and on pregnancy outcome in women with abortion. Materials and Methods: In this case-control study, 25 non-pregnant women with at least 3 abortions without obvious reason and 25 non-pregnant women with a living child without history of previous abortion participated. Using monoclonal antibodies anti (CD16, CD56 and CD20 and flow cytometry method, the percentage of cells with these markers was determined. Data analysis was performed by with SPSS 15 software and T-test. Results: CD16+, CD56+ and NK (CD16+/CD56+ cells significantly increased in women with RSA compared with control group (P≤0.05 but there were no significant differences in the percentage of B CD20+ cells between the experimental and control groups (P>0.05. Conclusion: According to the results of the present study, increased percentage of NK cells may be considered as a risk factor for RSA but involvement and the role of B CD20+ lymphocytes in RSA cannot be confirmed; however, in regard to important role of B and NK cell in the management of the immune responses, more studies are required to understand the behavior of these cells in the different stages of pregnancy more efficiently

  19. 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.

  20. CD20阳性淋巴细胞在慢性移植肾肾病组织中浸润的意义%Significance of CD20-positive lymphocytes infiltrating in renal allograft biopsies with chronic allograft nephropathy

    Institute of Scientific and Technical Information of China (English)

    胡建敏; 赵明; 郭颖; 陈桦; 李民

    2012-01-01

    目的 探讨肾移植术后慢性移植物肾病(CAN)组织CD20阳性淋巴细胞浸润的临床意义及其机制.方法 选择肾移植术后2年内活检证实为CAN病例为研究对象,应用免疫组织化学方法检测补体C4d的沉积和CD20阳性淋巴细胞在移植肾组织的浸润,同时分析临床随访资料.结果 人选CAN病例44例,其中CD20阳性淋巴细胞浸润13例(29.5%),CD20阴性为31例(70.5%),移植肾组织不同病理分级者中CD20阳性者所占比例的差异无统计学意义(P>0.05).44例中,12例(27.3%)出现管周毛细血管内皮细胞(PTC)补体C4d的线性沉积,CD20阳性和阴性者中补体C4d表达阳性率的差异无统计学意义(P>0.05).确诊为CAN时移植肾组织CD20为阴性和阳性者的肾功能分别为( 140.8±22.0)μmol/L和(183.5±25.5) μmol/L(P<0.01),1年后分别为(165.6±37.6)μmol/L和(242.2±59.1 )μmol/L(P<0.01).结论 CD20阳性淋巴细胞在移植肾组织的浸润与移植物的预后相关,其机制可能不是通过慢性体液免疫反应.%Objective To investigate the action mechanism of CD20 lymphocyte infiltration in the renal allograft biopsy with chronic allograft nephropathy (CAN).Methods CAN cases confirmed by renal biopsy within 2 years after renal transplantation served as study subjects. By using immunohistochemistry,the deposition of C4d and the CD20-positive lymphocytes infiltration in the renal grafts were examined.The clinical follow-up data were analyzed.Results Forty-four cases of CAN were enrolled in the study, including 13 cases (29.5% ) of CD20-positive lymphocytes infiltration,and 31 cases (70.5% ) of CD20-negative lymphocytes infiltration. CD20-positive lymphocytes in biopsy showed nodular and scattered lymphocytes infiltration.There were 5 (26.3%)cases of CAN Ⅰ,4 cases (25.0%) of CAN Ⅱ,and 4 (44.4%) of CAN Ⅲ in CD20-positive group.There was no statistically significant difference between the only CAN group and CAN with AR group in

  1. 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.

  2. 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

  3. 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)

  4. Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease.

    Energy Technology Data Exchange (ETDEWEB)

    Park, Steven I.; Shenoi, Jaideep; Pagel, John M.; Hamlin, Donald K.; Wilbur, D. Scott; Orgun, Nural; Kenoyer, Aimee L.; Frayo, Shani; Axtman, Amanda; Back, Tom; Lin, Yukang; Fisher, Darrell R.; Gopal, Ajay K.; Green, Damian J.; Press, Oliver W.

    2010-11-18

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 µCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p<0.0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.

  5. The study of conjugation of anti-CD20 monoclonal antibody for labeling with metallic or lanthanides radionuclides

    International Nuclear Information System (INIS)

    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®). 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®) 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)

  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. CD20 antigen expression by lymphoma cells in lung allograft recipients is associated with higher remission rate and superior survival: A study on heart and lung transplant recipients

    Directory of Open Access Journals (Sweden)

    Aghil Gholipour-Shoiili

    2014-01-01

    Full Text Available Post-transplant lymphoproliferative disorders (PTLD are one of the fatal complications of transplantation, and there is scarcity of data on the relevance of antigen expression by tumor cells in PTLD. In the current study, we aimed to investigate the potential effects of CD20 antigen expression by PTLD lesions developing in heart/lung transplant recipients. A comprehensive search was performed for reports indicating CD20 antigen tests in PTLD lesions developing in heart and/or lung transplant recipients. For data accumulation, we developed a standard questionnaire and data of patients presented in different published reports were entered into it. Finally, data from 26 previously published reports from different centers around the world were included in the analysis. CD20-positive PTLD lesions are significantly more likely to be of the B cell type (P = 0.006. PTLD in patients with a CD20-positive test represented relevantly shorter time from transplantation to PTLD, although it did not reach a significance level (P = 0.08. At the last follow-up, 53% patients were dead. Survival analysis showed no prognosis difference regarding CD20 test. When data were reanalyzed separately for heart and lung transplant recipients, lung recipients developing PTLD with a CD20-positive test were significantly more likely to represent remission episodes (P = 0.03, and also represented a significantly better outcome than CD20-negative PTLD patients (P = 0.04. CD20-positive PTLD lesions in heart/lung recipients are more likely of the B cell type and develop PTLD lesions earlier than their CD20-negative counterparts. Lung recipients developing CD20-positive PTLD lesions represented higher remission rates and better outcome. Further studies with prospective follow-up of patients are needed for confirming our findings.

  8. CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

    OpenAIRE

    Johnson, Nathalie A.; Leach, Stephen; Woolcock, Bruce; deLeeuw, Ronald J; Bashashati, Ali; Sehn, Laurie H.; Connors, Joseph M; Chhanabhai, Mukesh; Brooks-Wilson, Angela; Gascoyne, Randy D.

    2009-01-01

    The findings of this study indicate that CD20 mutations nvolving the rituximab epitope are rare in both de novo and relapsed diffuse large B-cell lymphoma, and do not represent a significant cause of R-CHOP resistance.

  9. 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.

  10. Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study.

    Science.gov (United States)

    Ceppi, Francesco; Weitzman, Sheila; Woessmann, Wilhelm; Davies, Kimberly; Lassaletta, Alvaro; Reismüller, Bettina; Mellgren, Karin; Uyttebroeck, Anne; Maia, Iris; Abdullah, Shaker; Miakova, Natasha; Glaser, Darryl; Cohn, Richard; Abla, Oussama; Attarbaschi, Andishe; Alexander, Sarah

    2016-05-01

    Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, post-transplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD20+ B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/intraventricular rituximab for patients with CNS involvement of CD20 + B lymphoid malignancies are warranted. Am. J. Hematol. 91:486-491, 2016. © 2016 Wiley Periodicals, Inc. PMID:26872652

  11. 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

  12. Impact of CD68/(CD3+CD20 ratio at the invasive front of primary tumors on distant metastasis development in breast cancer.

    Directory of Open Access Journals (Sweden)

    Noemí Eiró

    Full Text Available Tumors are infiltrated by macrophages, T and B-lymphocytes, which may favor tumor development by promoting angiogenesis, growth and invasion. The aim of this study was to investigate the clinical relevance of the relative amount of macrophages (CD68⁺, T-cells (CD3⁺ and B-cells (CD20⁺ at the invasive front of breast carcinomas, and the expression of matrix metalloproteases (MMPs and their inhibitors (TIMPs either at the invasive front or at the tumor center. We performed an immunohistochemical study counting CD3, CD20 and CD68 positive cells at the invasive front, in 102 breast carcinomas. Also, tissue sections were stained with MMP-2, -9, -11, -14 and TIMP-2 antibodies, and immunoreactivity location, percentage of reactive area and intensity were determined at the invasive front and at the tumor center. The results showed that an increased CD68 count and CD68/(CD3+CD20 ratio were directly associated with both MMP-11 and TIMP-2 expression by mononuclear inflammatory cells at the tumor center (p = 0.041 and p = 0.025 for CD68 count and p = 0.001 and p = 0.045 for ratio, respectively for MMP-11 and TIMP-2. In addition, a high CD68/(CD3+CD20 ratio (>0.05 was directly associated with a higher probability of shortened relapse-free survival. Multivariate analysis revealed that CD68/(CD3+CD20 ratio was an independent factor associated with distant relapse-free survival (RR: 2.54, CI: (1.23-5.24, p<0.01. Therefore, CD68/(CD3+CD20 ratio at the invasive front could be used as an important prognostic marker.

  13. 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。

  14. 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.

  15. 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.

  16. 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-

  17. 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

  18. CD20单克隆抗体在重症系统性红斑狼疮患儿治疗中的应用%Rituximab therapy for severe pediatric systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    苏改秀; 吴凤岐; 王芳; 周志轩; 黄小兰; 鲁杰

    2012-01-01

    目的 探讨CD20单克隆抗体(利妥昔单抗)治疗重症儿童系统性红斑狼疮(SLE)的有效性和安全性.方法 诊断依据1997年美国风湿病学会SLE的分类标准.纳入标准:年龄≤16岁,至少1个以上重要器官受累,SLEDA1评分>10分,常规治疗反应欠佳.治疗方法:抗CD20单抗剂量375 mg/(m2·次),于第0、14天分次静脉输注.于CD20单抗治疗前及治疗后2周、1、3、6、12个月评估疗效,并监测不良反应.结果 共20例SLE患儿,男女比1∶3,年龄5~16岁,病程(3.0±2.5)年,平均随访(27.0±7.8)个月.10例狼疮脑病患儿谵妄、认知障碍等在1个月内明显改善;15例狼疮肾炎患儿中14例用药2~3个月后改善,1例无明显缓解;4例狼疮肺炎患儿用药1个月内症状减轻;18例血细胞减少患儿中16例在1个月内恢复.95%患儿(19/20)2周内B细胞清除,90%患儿(18/20)B淋巴细胞计数于1年内恢复.SLEDAI评分用药后明显降低,用药1年泼尼松剂量从( 45.0±4.7)mg/m2降至(12.0 ±2.7) mg/m2(P<0.001).用药半年内5例患儿出现肺炎,其中2例重症肺炎分别为曲霉菌肺炎及卡氏肺囊虫肺炎,均治疗后好转,无死亡病例.随B细胞恢复,2例患儿分别于治疗15、18个月后病情反复,给予第2疗程抗CD20单抗后,1例病情再次缓解,另外1例病情缓解不明显.结论 抗CD20单抗治疗重症儿童SLE疗效肯定,耐受性较好,部分病例可能发生严重感染.%Objective To analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE). Method The diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria:age ≤ 16 years,number of important organs involved > 1,SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment

  19. 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.

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

    OpenAIRE

    Vellenga, Edo; van Putten, Wim; Veer, Mars; Zijlstra, Josée; Fibbe, Willem; Oers, Marinus; Verdonck, Leo; Wijermans, Pierre; van Imhoff, Gustaaf; Lugtenburg, Pieternella; 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- cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in c...

  1. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma.

    Directory of Open Access Journals (Sweden)

    Lihua E Budde

    Full Text Available Modification of T cells with chimeric antigen receptors (CAR has emerged as a promising treatment modality for human malignancies. Integration of co-stimulatory domains into CARs can augment the activation and function of genetically targeted T cells against tumors. However, the potential for insertional mutagenesis and toxicities due to the infused cells have made development of safe methods for removing transferred cells an important consideration. We have genetically modified human T cells with a lentiviral vector to express a CD20-CAR containing both CD28 and CD137 co-stimulatory domains, a "suicide gene" relying on inducible activation of caspase 9 (iC9, and a truncated CD19 selectable marker. Rapid expansion (2000 fold of the transduced T cells was achieved in 28 days after stimulation with artificial antigen presenting cells. Transduced T cells exhibited effective CD20-specific cytotoxic activity in vitro and in a mouse xenograft tumor model. Activation of the iC9 suicide switch resulted in efficient removal of transduced T cells both in vitro and in vivo. Our work demonstrates the feasibility and promise of this approach for treating CD20(+ malignancies in a safe and more efficient manner. A phase I clinical trial using this approach in patients with relapsed indolent B-NHL is planned.

  2. 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.

  3. CD20单克隆抗体联合CHOP化疗方案治疗人B细胞淋巴瘤的实验观察%Experimental therapy of human B-cell lymphomas with CD20 monoclonal antibody and CHOP protocol

    Institute of Scientific and Technical Information of China (English)

    高磊; 周倩; 钱卫珠; 范晓强; 郭亚军

    2008-01-01

    目的:以人B细胞淋巴瘤裸鼠皮下移植模型为基础,研究抗CD20单克隆抗体体内、体外活性,评价该抗体联合CHOP化疗方案治疗人B细胞淋巴瘤的有效性.方法:体内实验:建立人B细胞淋巴瘤裸鼠皮下移植模型.52只荷瘤鼠随机分为5组进行实验.用TUNEL法检测肿瘤凋亡,并绘制肿瘤体积曲线和裸鼠体质量曲线.体外实验:用CellTiter 96 AQueous非同位素细胞增殖试验试荆盒检测抗CD20单克隆抗体、化疗和联舍化疗对Raji细胞体外杀伤作用,并绘制荆量反应曲线.结果:体内实验:鼠抗人CD20单抗组及嵌合CD20抗体组均出现大量肿瘤细胞凋亡.联合治疗组疗效最佳,与其他组相比差异有统计学意义,P<0.05.化疗组及联合治疗组体质量下降明显,与其他组相比差异有统计学意义,P<0.05.体外实验:发现鼠抗人CD20单克隆抗体及嵌舍型CD20抗体均可增加Raji细胞对化疗药物的细胞毒敏感性.结论:CD20单克隆抗体对B细胞淋巴瘤具有明显的抑制作用,可以诱发大面积肿瘤细胞凋亡,能提高肿瘤对化疗药物的细胞毒敏感性,且较常规化疗毒副反应小.

  4. 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

  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. Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells

    OpenAIRE

    Roscher, Mareike; Hormann, Inis; Leib, Oliver; Marx, Sebastian; Moreno, Josue; Miltner, Erich; Friesen, Claudia

    2013-01-01

    Radioimmunotherapy (RIT) is an emerging treatment option for non-Hodgkin lymphoma (NHL) producing higher overall response and complete remission rates compared with unlabelled antibodies. However, the majority of patients treated with conventional or myeloablative doses of radiolabelled antibodies relapse. The development of RIT with alpha-emitters is attractive for a variety of cancers because of the high linear energy transfer (LET) and short path length of alpha-radiation in human tissue, ...

  7. 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.

  8. High-Dose 131I-Tositumomab (Anti-CD20) Radioimmunotherapy for Non-Hodgkin's Lymphoma: Adjusting Radiation Absorbed Dose to Actual Organ Volumes

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) using 131I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed close to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. Methods: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of 131I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar -camera images and whole-body Nal probe counts were obtained to estimate 131I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. Results: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs= 1.67; liver= 1.03; kidneys= 1.08; spleen= 2.67; and whole body= 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs= 1.30; liver= 0.92; kidneys= 0.76; spleen= 1.40; and whole body= 0.22. We determined the following correlation coefficients between the 2 methods for the various organs; lungs, 0.49; (P= 0.0001); liver, 0.64 (P= 0.004); kidneys, 0.45 (P= 0.0001), for the residence times. For therapy, patients received mean 131I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes--a statistically significant difference (P= 0.0001). Conclusion: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation doses by adjusting for the actual organ mass and shows the value of this approach in treatment planning for RIT

  9. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma

    DEFF Research Database (Denmark)

    Hagenbeek, Anton; Gadeberg, Ole Vestergaard; Johnson, Peter;

    2008-01-01

    lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment...

  10. 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.

  11. Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes. We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system. We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infitrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment. Our results suggest that alterations in lymphocyte

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann;

    2010-01-01

    The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The...

  18. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian;

    2013-01-01

    The treatment of chronic lymphocytic leukaemia (CLL) has been improved by introduction of monoclonal antibodies (mAbs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti-CD5 Abs that engage ...

  19. 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.

  20. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    Science.gov (United States)

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  1. Therapeutic Effect Evaluation of the Combination Regimen of Rituximab and CHOP for CD20 Positive Diffuse Large B-cell Lymphoma%R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤的临床疗效评价

    Institute of Scientific and Technical Information of China (English)

    刘爱学; 张容榕; 李明淑; 周泽强; 冯天举

    2012-01-01

    目的:观察利妥昔单抗联合CHOP方案(R-CHOP方案)初治弥漫大B细胞淋巴瘤的疗效及不良反应.方法:对20例初治弥漫大B细胞淋巴瘤患者,给予6周期~8周期R-CHOP方案治疗.利妥昔单抗375mg/m2,静滴,d1;环磷酰胺750mg/m2,iv,d1;阿霉素50mg/m2,iv,d1;长春新碱1.4mg/m2,iv,d1;强的松100mg/d,口服,d1-5;21天为一周期.结果:20例患者中,完全缓解13例,部分缓解3例,稳定1例,进展3例,客观缓解率80%.主要毒副反应为血液学毒性,轻度胃肠道反应,无利妥昔单抗不良反应.结论:R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤缓解率高,毒副反应可以耐受.%Objective: To observe the effect and toxicity of combination treatment of rituximab and CHOP-regimen for diffuse large B cell lymphoma( DLBCL ). Methods: 20 patients initially diagnosed as DLBCL received R-CHOP regimen of 6 - 8 cycles: rituximab 375mg/m intravenously infused on dayl, cyclophosphamide 750mg/m on clayl, adriamycin 50mg/m2 on clayl and vincristine 1. 4mg/m on day 1, prednisone lOOmg/d taken orally on day 1 ~5; 21days as one cycle. Results: In all 20 patients, 13 got complete response and 3 partial response, 1 SD, 3 PD. The overall response rate was 80. 0%. Main toxicity included myelosuppression, slightly gastrointestinal reaction. No rituximab related toxicity was observed in all the patients. Conclusion: R-CHOP regimen has high efficacy with mild toxicity in the treatment of initially diagnosed diffuse large B cell lymphoma.

  2. 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.

  3. 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.)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin

    Directory of Open Access Journals (Sweden)

    Massimo Bortolotti

    2016-06-01

    Full Text Available The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20+ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric and LMW-IT (monomeric maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates.

  9. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin.

    Science.gov (United States)

    Bortolotti, Massimo; Bolognesi, Andrea; Battelli, Maria Giulia; Polito, Letizia

    2016-01-01

    The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20⁺ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric) and LMW-IT (monomeric) maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates. PMID:27338475

  10. 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.

  11. After anti-racism?

    OpenAIRE

    Lentin, Alana

    2008-01-01

    Abstract Anti-racism as a political discourse and a form of collective social action has long been ignored as a serious field of research. In contrast, I envision the study of anti-racism as a vital lens on both 'race' and racism. First, the heterogeneity of anti-racism is demonstrated, spanning both pro- and anti-state-based analyses of the origins of racism. Second, a parallel discourse of 'anti-anti-racism' within the radical Left reveals the reluctance of many on the Left to id...

  12. 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

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

    OpenAIRE

    Basundari Sri Utami; Sekar Tuti; Anggita Bunga Anggraini; Mukhlissul Faatih; Siswanto Siswanto; Trihono Trihono

    2014-01-01

    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 mas...

  14. Anti-addiction vaccines

    OpenAIRE

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    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 ...

  15. Anti-nutritional Factors.

    Science.gov (United States)

    2016-01-01

    Anti-nutritional factors such as trypsin inhibitor, phytic acid and cyanogen are as important as nutritional content of any edible plant part. The anti-nutritional factors can be defined as those substances generated in natural food substances by the normal metabolism of species and by different mechanisms (e.g. inactivation of some nutrients, diminution of the digestive process or metabolic utilization of feed) which exert effects contrary to optimum nutrition. Hence, trypsin inhibitor, phytic acid and cyanogens present in edibles with the methods in the chapter would be helpful. PMID:26939264

  16. The Anti-Landscape

    DEFF Research Database (Denmark)

    humanities. The Anti-Landscape provides an interdisciplinary approach that moves beyond the false duality of nature vs. culture, and beyond diagnosis and complaint to the recuperation of damaged sites into our complex heritage. Collection of essays based on a conference held at SDU in 2011....

  17. Anti- CC-Groups and Anti-PC-Groups

    Directory of Open Access Journals (Sweden)

    Francesco Russo

    2007-01-01

    subgroup H of G. An anti-PC group G is a group in which each nonfinitely generated subgroup K has the quotient group G/coreG(NG(K which is a polycyclic-by-finite group. Anti-CC groups and anti-PC groups are the subject of the present article.

  18. 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

  19. Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Yusuf, Isharat; Akhgar, Ahmad; Wu, Yuling; Roskos, Lorin K; Herbst, Ronald; Wang, Yue

    2016-07-01

    B cell depletion therapy is beneficial for patients with B cell malignancies and autoimmune diseases. CD19, a transmembrane protein, is expressed on a vast majority of normal and neoplastic B cells, making it a suitable target for monoclonal antibody (MAb) mediated immunotherapy. We have developed MEDI-551, an affinity optimized and afucosylated IgG1 MAb targeting human CD19 for B cell depletion. MEDI-551 is currently under investigation in multiple clinical trials. Because MEDI-551 does not cross react with rodent and non-human primate CD19, the pharmacological characteristics of the MAb were evaluated in human CD19 transgenic mice (hCD19 Tg). Here we show that MEDI-551 potently depletes tissue and circulating B cells in hCD19 Tg mice and is more efficacious than the anti-CD19 MAb with intact fucose. The length of B cell depletion depends on MEDI-551 dose; and, B cell recovery in the circulation follows stepwise phenotypic maturation. Furthermore, intravenous (IV) and subcutaneous (SC) administration of MEDI-551 results in comparable efficacy. Lastly, the combination of MEDI-551 with the anti-CD20 MAb, rituximab, further prolongs the duration of B cell depletion. In summary, the pharmacological profile of MEDI-551 presented in hCD19 Tg mice supports further testing of MEDI-551 in clinical trials involving B cell malignancies and autoimmune diseases. PMID:27163209

  20. Anti-Microtubule Drugs.

    Science.gov (United States)

    Florian, Stefan; Mitchison, Timothy J

    2016-01-01

    Small molecule drugs that target microtubules (MTs), many of them natural products, have long been important tools in the MT field. Indeed, tubulin (Tb) was discovered, in part, as the protein binding partner of colchicine. Several anti-MT drug classes also have important medical uses, notably colchicine, which is used to treat gout, familial Mediterranean fever (FMF), and pericarditis, and the vinca alkaloids and taxanes, which are used to treat cancer. Anti-MT drugs have in common that they bind specifically to Tb in the dimer, MT or some other form. However, their effects on polymerization dynamics and on the human body differ markedly. Here we briefly review the most-studied molecules, and comment on their uses in basic research and medicine. Our focus is on practical applications of different anti-MT drugs in the laboratory, and key points that users should be aware of when designing experiments. We also touch on interesting unsolved problems, particularly in the area of medical applications. In our opinion, the mechanism by which any MT drug cures or treats any disease is still unsolved, despite decades of research. Solving this problem for particular drug-disease combinations might open new uses for old drugs, or provide insights into novel routes for treatment. PMID:27193863

  1. Prescription Nonsteroidal Anti-Inflammatory Medicines

    Science.gov (United States)

    MENU Return to Web version Prescription Nonsteroidal Anti-Inflammatory Medicines Prescription Nonsteroidal Anti-Inflammatory Medicines How do prescription nonsteroidal anti-inflammatory drugs work? Nonsteroidal anti-inflammatory drugs (also called NSAIDs) stop cyclooxygenase ...

  2. Anti-inflammatory Activity.

    Science.gov (United States)

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  3. Anti-Sharing

    OpenAIRE

    Kirstein, Roland; Cooter, Robert

    2005-01-01

    The paper proposes a mechanism that may implement first-best effort in simultaneous teams. Within the framework of this mechanism, each team members is obliged to make a fixed, non-contingent payment, and chooses his individual effort. After the output is produced, each team member receives a gross payment that equals the actual team output. We demonstrate that a Nash equilibrium exists in which each team member chooses first-best effort. We call this mechanism ?Anti-Sharing? since it solves ...

  4. 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.

  5. Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

    Science.gov (United States)

    Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

    2015-02-01

    Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

  6. Anti-androgen treatments.

    Science.gov (United States)

    Bachelot, Anne; Chabbert-Buffet, Nathalie; Salenave, Sylvie; Kerlan, Véronique; Galand-Portier, Marie-Béatrice

    2010-02-01

    1. Estrogen plus progestin contraceptives (EPP) are the first-line treatment of moderate hirsutism and acne in women of child bearing age (grade C). 2. CPA, 50mg/day, 20 days out of 28, associated with estrogen is the first-line treatment of "moderate to severe hirsutism" in women of childbearing age (grade C). 3. Spironolactone, given as a contraceptive, can be proposed as a second-line treatment in case of side effects or counter-indications to CPA in moderate to severe hirsutism (grade C) in women of childbearing age. No market authorization in this indication. 4. Flutamide or Finasteride are "only" to be used under the guise of contraception as a "thirdline therapy" in cases of severe hirsutism, the presence of side effects or counter-indications to EPP, CPA 50mg/day or spironolactone (grade C). No market authorization in this indication 5. There is no indication for GnRH analogs as an anti-androgen treatment in women of childbearing age given the current therapeutic alternatives (grade C) 6. Only long-term hair removal treatments can be proposed (grade C): electrolysis or laser hair removal. PMID:20096826

  7. Anti-parallel triplexes

    DEFF Research Database (Denmark)

    Kosbar, Tamer R.; Sofan, Mamdouh A.; Waly, Mohamed A.;

    2015-01-01

    -parallel TFO strand was modified with Y with one or two insertions at the end of the TFO strand, the thermal stability was increased 1.2 °C and 3 °C at pH 7.2, respectively, whereas one insertion in the middle of the TFO strand decreased the thermal stability 1.4 °C compared to the wild type oligonucleotide......-1-yl chain, especially at the end of the TFO strand. On the other hand, the thermal stability of the anti-parallel triplex was dramatically decreased when the TFO strand was modified with the LNA monomer analog Z in the middle of the TFO strand (ΔTm = -9.1 °C). Also the thermal stability...... decreased about 6.1 °C when the TFO strand was modified with Z and the Watson-Crick strand with adenine-LNA (AL). The molecular modeling results showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72 Å, respectively) was formed between the protonated 3-aminopropyn-1-yl chain...

  8. 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.

  9. The anti pp yields anti λ λ reaction near threshold

    International Nuclear Information System (INIS)

    Measurements of differential and integrated cross sections as well as final state polarizations for the anti p p → anti Λ Λ reaction are presented. The reaction was studied at two incident antiproton momenta (1476.5 MeV/c and 1507.5 MeV/c) corresponding to total center of mass energies of 15.5 MeV and 26.4 MeV above the reaction threshold. The trajectories of charged decay products of the anti Λ and Λ were observed in a multiwire proportional chamber and in two sets of drift chambers. The data were analyzed with a computer program which reconstructed anti p p → anti Λ Λ → anti p π+pπ- events and performed kinematic fitting. The results are compared to several recent meson exchange calculations, and a one-gluon exchange calculation. The experiment was performed at the Low Energy Antiproton Ring (LEAR) at CERN. The data presented represent the first results of the PS185 collaboration's study of the threshold production of hyperon-antihyperon states

  10. Study of anti-deuterons, anti-tritons and anti-{sup 3}He at Belle

    Energy Technology Data Exchange (ETDEWEB)

    Kuenze, Stephanie; Galuska, Martin; Gessler, Thomas; Kuehn, Wolfgang; Lange, Jens Soeren; Muenchow, David; Semmler, Diego; Spruck, Bjoern; Ullrich, Matthias; Werner, Marcel [2. Physikalisches Institut, Universitaet Giessen (Germany)

    2010-07-01

    Events of the type e{sup +}e{sup -}{yields} anti d+X, anti t+X, anti-{sup 3}He+X, are rare events in e{sup +}e{sup -} collisions as they require the production of several anti-quarks together with their corresponding quarks (6+6 in the deuteron case, 9+9 for triton and {sup 3}He). In addition, in order to form a bound state, the anti-quarks must be close in phasespace, so that coalescence (i.e. overlap of the wave functions) can be applied. Preliminary results from Belle at {radical}(s){approx_equal}10.6 GeV with a data set of 589fb{sup -1}, using dE/dx in the Belle drift chamber for particle identification, are presented. The momentum distribution of the anti-nuclei can be compared to a fireball model. Preliminary results of the search for anti-{sup 4}He are also presented.

  11. Neue Anti-Spam-Techniken

    OpenAIRE

    Richter, Frank

    2004-01-01

    Workshop "Netz- und Service-Infrastrukturen" Dieser Beitrag zum Workshop "Netz- und Service-Infrastrukturen" 2004 analysiert den Stand der Anti-Spam-Maßnahmen an der TU Chemnitz und zeigt neue Techniken auf.

  12. Online Anti-Brand Herds

    DEFF Research Database (Denmark)

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

    The online environment offers a fertile breeding ground for anti-brand herds of disgruntled consumers. Firms are often caught off guard by the unpredictability of such herds and, as a consequence, are forced into a reactive, defensive stance. We conduct a social media analysis that aims to shed...... 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...... 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...

  13. Anti-reflux surgery - children

    Science.gov (United States)

    ... stomach). Problems with these muscles can lead to gastroesophageal reflux disease (GERD). This surgery can also be done during a ... Anti-reflux surgery is usually done to treat GERD in children only after medicines have not worked ...

  14. Anti Rh Hemolytic Disease due to Anti C Antibody: Is Testing for Anti D Antibodies Enough?

    OpenAIRE

    Negi, Gita; Singh, Gaur Dushyant

    2011-01-01

    Rh blood group system is a complex blood group system. Rh antibodies are produced in Rh negative individuals following exposure to foreign RBCs after transfusion or pregnancy. Anti C is a rare cause of hemolytic disease of newborn and is very scarcely reported in the literature. The aim of the present case report of Hemolytic disease caused by Anti C antibody is to bring out the fact that antibodies other than anti D should be considered in cases that give a suggestive history but no evidence...

  15. Solidarity, authenticity and anti racism

    OpenAIRE

    Dinesh Wadiwel

    2009-01-01

    Anti Racist struggles often aim to construct alliances between groups under the banner of "solidarity" in order to achieve change. Using Foucault's Society Must be Defended lectures as a basis, this paper interrogates the difficulties associated with creating solidarity in anti racist movements, when conflict and war might be treated as the basis for racial stratifications. Following from this, it is argued that friendships in spite of differences are possible under the guise of "truce": that...

  16. Anti-inflammatory and anti-cancer activity of mulberry (Morus alba L.) root bark

    OpenAIRE

    Eo, Hyun Ji; Park, Jae Ho; Park, Gwang Hun; Lee, Man Hyo; Lee, Jeong Rak; Koo, Jin Suk; Jeong, Jin Boo

    2014-01-01

    Background Root bark of mulberry (Morus alba L.) has been used in herbal medicine as anti-phlogistic, liver protective, kidney protective, hypotensive, diuretic, anti-cough and analgesic agent. However, the anti-cancer activity and the potential anti-cancer mechanisms of mulberry root bark have not been elucidated. We performed in vitro study to investigate whether mulberry root bark extract (MRBE) shows anti-inflammatory and anti-cancer activity. Methods In anti-inflammatory activity, NO was...

  17. 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.

  18. Anti-abortion movement.

    Science.gov (United States)

    Wilson, K

    1985-01-01

    At the same time that American women celebrate the freedoms won thus far for so many Americans, American women must realize they face some of the greatest threats to liberty in recent memory. To understand this movement against American women, it is necessary to first understand the roots of the historic movement for women's rights. Reproductive freedom for many years topped the agenda of the modern women's movement. At a time and in a land where rights were being enriched and liberty prized, choice took a prominent role, specifically, the right to abortion but also generally to repdocuctive freedom and the many underlying issues involved. This is why the various efforts to criminalize abortion effect every citizen, because they pose a serious threat to the constitutional rights of each individual. This is the intellectual view, or the "head" argument. The Constitution states that: "Congress shall make no laws respecting an establishment of religion, or prohibiting the free exercise thereof; the enumeration in the Constitution, of certain rights, shall not be construed to deny or disparage others retained by the people; and no state shall make or enforce any laws which shall abridge the privileges or immunities of citizens of the US." Each of these clauses expresses the philosophy on which the Constitution was founded -- individual liberty. While there has been some legitimate disagreement over what constitutes an inalienable right, the concept is clear: the government should not become involved in personal philosophical or religious matters, except to permit the freedom of personal philosophical or religious expression. The anti-abortion contignent makes its case by claiming that a fertilized egg is a cona fide person and should, therefore, be guaranteed the Constitution's full roster of protections. In its landmark Roe v. Wade opinion, the Supreme Court held what pro-choice activities have been claiming for years. Since there is no empirical test by which measure

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

    OpenAIRE

    Blagosklonny, Mikhail V.

    2013-01-01

    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 inv...

  20. On Mathematical Anti-Evolutionism

    Science.gov (United States)

    Rosenhouse, Jason

    2016-03-01

    The teaching of evolution in American high schools has long been a source of controversy. The past decade has seen an important shift in the rhetoric of anti-evolutionists, toward arguments of a strongly mathematical character. These mathematical arguments, while different in their specifics, follow the same general program and rely on the same underlying model of evolution. We shall discuss the nature and history of this program and model and describe general reasons for skepticism with regard to any anti-evolutionary arguments based upon them. We shall then survey the major arguments used by anti-evolutionists, to show how our general considerations make it possible to quickly identify their weakest points.

  1. 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...

  2. 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. PMID:26972261

  3. 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.

  4. 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....

  5. Solidarity, authenticity and anti racism

    Directory of Open Access Journals (Sweden)

    Dinesh Wadiwel

    2009-08-01

    Full Text Available Anti Racist struggles often aim to construct alliances between groups under the banner of "solidarity" in order to achieve change. Using Foucault's Society Must be Defended lectures as a basis, this paper interrogates the difficulties associated with creating solidarity in anti racist movements, when conflict and war might be treated as the basis for racial stratifications. Following from this, it is argued that friendships in spite of differences are possible under the guise of "truce": that is through allegiances that begin by acknowledging the fact of war.

  6. Skin anti-aging strategies

    OpenAIRE

    Ganceviciene, Ruta; Liakou, Aikaterini I.; Theodoridis, Athanasios; Makrantonaki, Evgenia; Zouboulis, Christos C.

    2012-01-01

    Skin aging is a complex biological process influenced by a combination of endogenous or intrinsic and exogenous or extrinsic factors. Because of the fact that skin health and beauty is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have been developed during the last years. It is the intention of this article to review the most important anti-aging strategies that dermatologists have nowadays in...

  7. 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.

  8. Acute hemolytic transfusion reactions due to multiple alloantibodies including anti-E, anti-c and anti-Jkb.

    Science.gov (United States)

    Park, Tae Sung; Kim, Ki Uk; Jeong, Woo Jin; Kim, Hyung Hoi; Chang, Chulhun L; Chung, Joo Seop; Cho, Goon Jae; Lee, Eun Yup; Son, Han Chul

    2003-12-01

    We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients. PMID:14676451

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

    OpenAIRE

    Airò, P; R. Gorla; M. Vianelli; M. Frassi; Danieli, E; F. Franceschini; I. Cavazzana; Cattaneo, R

    2011-01-01

    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 w...

  10. 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

  11. The Scientist as Anti-Hero

    Science.gov (United States)

    Goran, Morris

    1976-01-01

    Suggests a new strategy for the proponents of science to rebut the cultural anti-science wave. This strategy involves publicizing the anti-hero scientist and presents a number of candidates from the past as examples. (GS)

  12. Laparoscopic Anti-Reflux (GERD) Surgery

    Science.gov (United States)

    ... Exhibit Opportunities Sponsorship Opportunities Login Laparoscopic Anti-Reflux (GERD) Surgery Patient Information from SAGES Print PDF Find ... to have laparoscopic anti-reflux surgery What is Gastroesophageal Reflux Disease (GERD)? Although “heartburn” is often used to ...

  13. Immunotherapy of non-Hodgkin's lymphoma with hLL2 (epratuzumab, an anti-CD22 monoclonal antibody) and Hu1D10 (apolizumab).

    Science.gov (United States)

    Leonard, John P; Link, Brian K

    2002-02-01

    Clinical activity of anti-CD20 monoclonal antibodies both in the unlabeled (rituximab [Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA]) and radiolabeled forms, as well as radioimmunoconjugates targeting other antigens, has resulted in the exploration of alternative targets for immunotherapeutic strategies in lymphoma. We report on the rationale for and initial efforts in the development of two unlabeled, humanized monoclonal antibodies directed against molecules commonly expressed in B-cell malignancies. hLL2 (epratuzumab; Immunomedics, Inc, Morris Plains, NJ) binds to the CD22 antigen, while Hu1D10 (apolizumab; Protein Design Labs, Inc, Fremont, CA) reacts with a polymorphism on the HLA-DR beta chain. Preclinical studies and early clinical evaluations suggest that these agents have a potential role as novel therapeutic targets for lymphoma with acceptable toxicity profiles. Further efforts will explore optimal clinical settings for their use, as well as define treatment regimens either as single agents or in combination with chemotherapy or other biologics. PMID:11842393

  14. 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.

  15. Clinical Scenarios for Discordant Anti-Xa

    OpenAIRE

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

    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 co...

  16. 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...

  17. Anti-spoofing: Fingerprint Databases

    OpenAIRE

    GALBALLY HERRERO JAVIER

    2013-01-01

    Anti-spoofing may be defined as the pattern recognition problem of automatically differentiating between real and fake biometric samples produced with a synthetically manufactured artefact (e.g., latex or silicone finger). As in any other machine learning problem the availability of data is a critical factor to be able to successfully address this challenging task. Furthermore, these data should be public, so that the performance of different protection methods may be compared in a fully fair...

  18. 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...

  19. 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.

  20. The anti-Einstein equations

    OpenAIRE

    Chaliasos, Evangelos

    2006-01-01

    As we know, from the Einstein equations the vanishing of the four-divergence of the energy-momentum tensor follows. This is the case because the four-divergence of the Einstein tensor vanishes identically. Inversely, we find that from the vanishing of the four-divergence of the energy-momentum tensor not only the Einstein equations follow. Besides, the so-named anti-Einstein equations follow. These equations must be considered as complementary to the Einstein equations. And while from the Ein...

  1. The anti-zombie argument

    OpenAIRE

    Frankish, Keith

    2007-01-01

    The zombie argument has come to occupy a central role in the case for a non-physicalist view of consciousness. This paper seeks to turn the tables on defenders of the argument ('zombists') by showing that a parallel argument can be run for physicalism. The argument invokes what I call anti-zombies – purely physical creatures that are nonetheless conscious. I show that, using the same resources as those employed by zombists, it is possible to construct an argument from the conceivability of an...

  2. Various Anti IP Spoofing Techniques

    OpenAIRE

    Patel, Sonal; Jha, Vikas

    2015-01-01

    Anti IP Spoofing techniques prevent your system or your Network from the IP Spoofing. IP Spoofing is attack that takes place in Network. It is used to gain unauthorized access to computer by spoofing the IP Address from the IP (Internet Protocol) Packet Header. The main Purpose of IP Spoofing attack is to hide the true identity of the attacker. IP Spoofing is used by the popular attacks like Dos (Denial o Service), DDos (Distributed Denial of Service), and Man in Middle. This Paper Describe v...

  3. Hemolytic disease of the fetus and newborn caused by anti-D and anti-S alloantibodies: a case report

    OpenAIRE

    Yousuf Rabeya; Abdul Aziz Suria; Yusof Nurasyikin; Leong Chooi-Fun

    2012-01-01

    Abstract Introduction Hemolytic disease of the fetus and newborn is most commonly caused by anti-D alloantibody. It is usually seen in Rhesus D (RhD)-negative mothers that have been previously sensitized. We report here a case of hemolytic disease of the fetus and newborn in a newborn baby caused by anti-D and anti-S alloantibodies, born to a mother who was RhD negative, but with no previous serological evidence of RhD alloimmunization. Case presentation A one-day-old Chinese baby boy was bor...

  4. 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.

  5. Search for new physics in anti b → anti s e+e- decays

    International Nuclear Information System (INIS)

    In summer 2014 the LHCb collaboration published their results on the measurement of the observable RK = B(anti B → anti Kμ+μ-)/B(anti B → anti Ke+e-), which revealed a deviation of 2.6σ from the Standard Model prediction. I check whether the deviation can be explained by scalar and pseudo-scalar dimension-six operators and investigate constraints from other measurements in a model-independent way. Furthermore, I analyse the contributions of the new operators to the angular distribution of anti B → anti Ke+e- decays.

  6. [Anti-inflammatory and anti-allergic oral vaccines?].

    Science.gov (United States)

    Lomholt, H B; Kilian, M

    1996-09-16

    Recent data suggest clinical efficacy of specific antigens delivered at mucosal sites in the treatment of certain organ specific autoimmune diseases. This approach appears non-toxic and has no side effects. Phase I/II human trials on multiple sclerosis and rheumatoid arthritis show positive outcomes. Furthermore, animal studies point to beneficial effects on uveitis, diabetes mellitus, transplantation reactions and allergic diseases. The immunological mechanism is oral tolerance, a well known principle for induction of a systemic hyporesponse to specific antigens. The tolerance is most pronounced on delayed type hypersensibility and IgE-mediated reactions. At least three different mechanisms mediate the tolerance. Low doses of antigen induce active suppression, intermediate doses induce clonal T-cell anergy, and high doses induce clonal T-cell deletion. The recent improvements in the understanding of the mechanisms of oral tolerance have fueled an interest in manipulating this principle to develop anti-inflammatory vaccines. PMID:8966773

  7. Atypical anti-glomerular basement membrane disease

    OpenAIRE

    Troxell, Megan L.; Donald C Houghton

    2015-01-01

    Background Anti-glomerular basement membrane (anti-GBM) disease classically presents with aggressive necrotizing and crescentic glomerulonephritis, often with pulmonary hemorrhage. The pathologic hallmark is linear staining of GBMs for deposited immunoglobulin G (IgG), usually accompanied by serum autoantibodies to the collagen IV alpha-3 constituents of GBMs. Methods Renal pathology files were searched for cases with linear anti-GBM to identify cases with atypical or indolent course. Histopa...

  8. Anti cytokine therapy in chronic inflammatory arthritis.

    Science.gov (United States)

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  9. 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. PMID:24485071

  10. Aromatase inhibitors and anti-synthetase syndrome.

    Science.gov (United States)

    Mascella, Fabio; Gianni, Lorenzo; Affatato, Alessandra; Fantini, Manuela

    2016-09-01

    Adjuvant therapy in postmenopausal women with endocrine-responsive breast cancer (BC) is actually centered on the use of anti-aromatase inhibitors (AI). Several reports, however, are emerging in literature associating the use of this drugs to rheumatic disorders. This case report describes the first case of anti-synthetase syndrome diagnosis after treatment with anti-estrogen agents in a patient with pre-existing rheumatoid arthritis. PMID:27225465

  11. 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.

  12. On Anti-Elite Prime Numbers

    Science.gov (United States)

    M"Uller, Tom

    2007-09-01

    An odd prime number p is called anti-elite if only finitely many Fermat numbers are quadratic non-residues to p. This concept is the exact opposite to that of elite prime numbers. We study some fundamental properties of anti-elites and show that there are infinitely many of them. A computational search among all the numbers up to 100 billion yielded 84 anti-elite primes.

  13. Evidence for Clinical Use of Honey in Wound Healing as an Anti-bacterial, Anti-inflammatory Anti-oxidant and Anti-viral Agent: A Review

    OpenAIRE

    Yaghoobi, Reza; Kazerouni, Afshin; kazerouni, Ory

    2013-01-01

    Context To provide an updated review of published literature on the anti-oxidant, anti-bacterial and anti-inflammatory properties of honey. Evidence Acquisition CINAHL, BioMed Central, Cochrane Library, Medline and Embase data bases and reference lists were used to find randomized controlled trials and review articles. Randomized controlled trials using honey with a comparator were reviewed, along with published review articles to determine the relative benefits of tropical honey. These metho...

  14. 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.

  15. In vitro screening for anti-acetylcholiesterase, anti-oxidant, anti-glucosidase, anti-inflammatory and anti-bacterial effect of three traditional medicinal plants

    OpenAIRE

    Ghareeb, Doaa A; ElAhwany, Amani M.D.; El-mallawany, Sherif M.; Saif, Ashraf A.

    2014-01-01

    In this study we investigated the phytoconstituents Calluna vulgaris, Ferula hermonis and Tribulus terrestris, and then assessed their possible biological activities by using standard methods. A preliminary phytochemical investigation of the three extracts revealed the presence of alkaloids, flavonoids, proteins, lipids, phenolic compounds, saponins, sterols and amino acids. Three extracts showed anti-oxidant effect as they inhibited the 1,1-diphenyl-2-picryl hydrazyl (DPPH) oxidation and pro...

  16. 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

  17. 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...

  18. 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...

  19. Developing Anti-tick Vaccines.

    Science.gov (United States)

    Rodríguez-Mallon, Alina

    2016-01-01

    Ticks are responsible for the transmission of viral, bacterial, and protozoal diseases of man and animals and also produce significant economic losses to cattle industry. The use of acaricides constitutes a major component of integrated tick control strategies. However, this is accompanied by the selection of acaricide-resistant ticks and contamination of environment and milk and meat products with drug residues. These issues highlight the need for alternative approaches to control tick infestations and have triggered the search for tick protective antigens for vaccine development. Vaccination as a tick control method has been practiced since the introduction of TickGARD and Gavac that were developed using the midgut glycoprotein Bm86 as antigen. Gavac within integrated tick management systems has proven to reduce the number of acaricidal applications per year that are required to control some strains of R. microplus ticks in different geographical regions. Nevertheless, it has limited or no efficacy against other tick species. These issues have stimulated research for additional tick protective antigens with critical functions in the tick. This chapter presents methodologies for the design and test of molecules as antigens against ticks. Considerations about different methods for the tick control compared to the immunological methods, the desirable characteristics for an anti-tick vaccine and the obstacles encountered for developing this kind of vaccines are discussed. Detailed methodologies for the establishment of a biological model to test new molecules as immunogens against ticks and to perform challenge trials with this model are presented. General considerations in the efficacy calculation for any anti-tick vaccine are also discussed. PMID:27076303

  20. Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

    OpenAIRE

    Reyin Lien; Yao-Lung Chang; Szu Ying Ho; Angel Chao; An-Shine Chao

    2010-01-01

    We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebra...

  1. 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

    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...

  2. 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.

  3. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M. (Santa Fe, NM)

    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.

  4. 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.

  5. Using Anti-VEGF in Diabetic Retinopathy

    Science.gov (United States)

    Marashi, Ameen

    2016-01-01

    Vascular endothelium growth factor is the main pathological factor in diabetic retinopathy and diabetic macular edema (DME), Anti-VEGF agents are safe and effective in DME treatment, there are multiple Anti-VEGF agents, choosing between them is essential to individualize treatment for each patient to achieve the optimum results. PMID:27419238

  6. 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.

  7. Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

    Science.gov (United States)

    Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

    2016-10-01

    Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. PMID:27208884

  8. 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.

  9. Anti-screening ferromagnetic superconductivity

    CERN Document Server

    Olesen, P

    2013-01-01

    We consider the Ginzburg-Landau mean field theory of ferromagnetic superconductors with complex order parameter $\\psi_i, i=1,2,3$. Below the critical temperature superconductivity is generated by means of a tachyonic term in the free energy $-\\alpha |\\psi_i|^2$ $(\\alpha>0)$, stabilized by a $\\psi^4$-term. However, we show that when $\\alpha$ becomes negative superconductivity can also be generated spontaneously by the magnetic field through the Zeeman like coupling between the field and the spin of the order parameter, in analogy with what happens in W-meson condensation. We also show that this mechanism leads to a vortex lattice which has anti-screening currents, enhancing the magnetic field instead of counteracting it. The lattice of vortices is a collective phenomenon where the individual elements do not exist in isolated form. If the parameter $\\alpha$ vanishes it is possible to obtain an explicit form of the vortex lattice in terms of Weierstrass' p-function.

  10. 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.

  11. 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.

  12. Anti-infective Natural Products from Cyanobacteria.

    Science.gov (United States)

    Niedermeyer, Timo Horst Johannes

    2015-10-01

    Cyanobacteria are a promising yet underexplored source for novel natural products with potent biological activities. While predominantly cytotoxic compounds have been isolated from cyanobacteria in the past, there are also a significant number of compounds known that possess anti-infective activities. As the need for novel anti-infective lead compounds is high, this manuscript aims at giving a concise overview on the current knowledge about anti-infective secondary metabolites isolated from cyanobacteria. Antibacterial, antifungal, antiviral, antiprotozoal, and molluscicidal activities are discussed. Covering up to February 2015.

  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.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.

  14. Human rights against anti-terrorist laws

    OpenAIRE

    Georg Friðgeir Ísaksson

    2009-01-01

    In this essay I will try to answer the question: Are human rights in the UK in jeopardy because of the nation’s increasing anti-terrorist laws? I will focus on the UK, how anti-terrorist laws have been implemented and how they have been used in the UK after the events of the terrorist attacks on 9/11. I chose the UK because of its long tradition of anti-terrorist laws since their dealings with the IRA in the last few decades of the last century. I wanted to take a look at different count...

  15. 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%.

  16. 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

  17. 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....

  18. 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.

  19. Anti-C1q autoantibodies.

    Science.gov (United States)

    Kallenberg, Cees G M

    2008-09-01

    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 condition. They occur, however, more frequently in (proliferative) lupus nephritis, particularly during active disease. Furthermore, levels of anti-C1q rise, in many cases, prior to a relapse of lupus nephritis, suggesting a pathogenic role for the autoantibodies. Indeed, experimental studies strongly support a pathogenic role for anti-C1q in immune complex-mediated renal disease. In addition, anti-C1q may interfere with the clearance of apoptotic cells, so influencing induction and expression of autoimmunity. PMID:18606253

  20. U.S. Anti-Doping Agency

    Science.gov (United States)

    ... does USADA do? What elements make USADA the gold standard in anti-doping and a leader in the fight for the integrity of competition and clean sport? Find Out Education Drug Reference TUEs Testing / Sample Collection ...

  1. 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...

  2. ASACUSA Anti-protonic Helium_Final

    CERN Multimedia

    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

  3. 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

  4. 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.

  5. 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.)

  6. 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.

  7. Entanglement in joint Λ anti Λ decay

    International Nuclear Information System (INIS)

    We investigate the joint Λ anti Λ decay in the reaction e+e- → γΛ(→ pπ-) anti Λ(→ anti pπ+). 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.)

  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. 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.

  10. Preeclampsia and the Anti-Angiogenic State

    OpenAIRE

    Agarwal, Isha; Karumanchi, S. Ananth

    2011-01-01

    Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide, however, its etiology remains unclear. Abnormal placental angiogenesis during pregnancy resulting from high levels of anti-angiogenic factors, soluble Flt1 (sFlt1) and soluble endoglin (sEng), has been implicated in preeclampsia pathogenesis. Accumulating evidence also points to a role for these anti-angiogenic proteins as serum biomarkers for the clinical diagnosis and prediction of preeclampsia. Uncoverin...

  11. 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).

  12. Aspherical Photon and Anti-Photon Surfaces

    CERN Document Server

    Gibbons, G W

    2016-01-01

    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.

  13. 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.

  14. 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.

  15. Anti-aircraft Missiles and Gun Control

    OpenAIRE

    BLOCK, Walter

    2016-01-01

    Abstract. Gun control is a highly debatable topic both in the popular and scholarly media. But what about anti-aircraft missiles? Should they be banned? On the one hand, there are fewer of them around, so their challenge is more tractable. On the other hand, they can do far more damage than handguns. The present paper is an attempt to wrestle with this challenge.Keywords. Gun control, Second amendment, Libertarianism, Anti-aircraft missiles.JEL. K15.

  16. New Anti-Merger Theories: A Critique

    OpenAIRE

    Edward J. López

    2005-01-01

    The purpose of this paper is to evaluate two new anti-merger instruments, innovation markets and unilateral effects, on the basis of economic theory and evidence. I first discuss how the economics of antitrust has developed over the years, with the intention of characterizing the intellectual inheritance of 1990s’ antitrust regulators. Within this context, I then discuss each anti-merger instrument, how it has been applied in specific cases, and how it accords with underlying economic science...

  17. Investigation of the reaction anti pp→anti YY close to threshold at LEAR

    International Nuclear Information System (INIS)

    For the reaction anti pp → anti ΛΛ from threshold up to 1.7 GeV/c total and different cross section data, polarisations and spin correlations have been obtained. The data indicate a remarkably strong p-wave contribution even close to the reaction threshold. The anti Λ-Λ spin correlations are compatible with a pure triplet state. (orig.)

  18. Heparin Alters Viral Serpin, Serp-1, Anti-Thrombolytic Activity to Anti-Thrombotic Activity

    OpenAIRE

    Li, Xing; Schneider, Heather; Peters, Andrew; Macaulay, Colin; King, Elaine; Sun, Yunming; Liu, Liying; Dai, Erbin; Davids, Jennifer A; McFadden, Grant; Lucas, Alexandra

    2008-01-01

    Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and...

  19. Sterols from Mytilidae Show Anti-Aging and Neuroprotective Effects via Anti-Oxidative Activity

    OpenAIRE

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

    2014-01-01

    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 experim...

  20. Anti-foam System design description

    International Nuclear Information System (INIS)

    The Anti-foam System is a sub-system of the 242-A Evaporator facility. The Anti-foam is used within the C-A-1 Vapor-Liquid Separator, to reduce the effect of foaming and reduce fluid bumping while the vapor and liquid are separated within the C-A-1 Vapor-Liquid Separator. Excessive foaming within the vessel may possibly cause the liquid slurry mixture in the evaporator vessel to foul the de-entrainment pads and cause plant shutdown. The Anti-foam System consists of the following primary elements: the Anti-foam Tank and the Metering Pump. The upgrades to Anti-foam System include the following: installation of a new pump, instruments, and valves; and connection of the instruments, pump and agitator associated with the Anti-foam System to the Monitoring and Control System (MCS). The 242-A Evaporator is a waste treatment facility designed to reduce liquid waste volumes currently stored in the Hanford Area double shell Waste Storage Tanks. The evaporator uses evaporative concentration to achieve this volume reduction, returning the concentrated slurry to the double-shell tanks for storage and, at the same time, releasing the process effluent to a retention facilities for eventual treatment and release to the environment

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

    OpenAIRE

    Adiyyatu Sa′idu Usman; Rapiaah Mustaffa; Noraida Ramli; Diggi, Sirajo A.

    2013-01-01

    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 wit...

  2. 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.

  3. 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.

  4. 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.

  5. 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…

  6. 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

  7. 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.

  8. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas

    International Nuclear Information System (INIS)

    New drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. We used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays. Curcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth. Curcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas

  9. 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.

  10. 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

  11. Gauge theories in anti-selfdual variables

    CERN Document Server

    Bochicchio, M

    2013-01-01

    Some years ago the Nicolai map, viewed as a change of variables from the gauge connection in a fixed gauge to the anti-selfdual part of the curvature, has been extended by the first named author to pure YM from its original definition in N=1 SUSY YM. We study here the perturbative 1PI effective action in the anti-selfdual variables of any gauge theory, in particular pure YM, QCD and N=1 SUSY YM. We prove that the one-loop 1PI effective action of a gauge theory mapped to the anti-selfdual variables in any gauge is identical to the one of the original theory. This is due to the conspiracy between the Jacobian of the change to the anti-selfdual variables and an extra functional determinant that arises from the non-linearity of the coupling of the anti-selfdual curvature to an external source in the Legendre transform that defines the 1PI effective action. Hence we establish the one-loop perturbative equivalence of the mapped and original theories on the basis of the identity of the one-loop 1PI effective actions...

  12. Anti-icing performance of superhydrophobic surfaces

    International Nuclear Information System (INIS)

    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 ∼80 μm) 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.

  13. 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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Arun kumar M

    2014-09-01

    Full Text Available 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: Ethanolic extract of Zingiber and Decalepis showed: (a Maximum zone of inhibition of 20 mm and 24 mm respectively, (b MIC of 5% and 2.5%respectively, (C Protein denaturation assay value (IC50 of 115 and 80 respectively. Conclusion: Ethanolic extract of Zingiber and Decalepis was found to possess both anti bacterial and anti-inflammatory potential against E. faecalis.

  16. 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.

  17. 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.

  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. 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...... and Results: The anti-adhesive activity was assayed against Escherchia coli K-12, and bacterial adhesion was quantified by crystal violet staining and sonication methods. Proteolytic digestion, elution and fractionation experiments revealed that the anti-adhesive activity of the extract was linked...... 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...

  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. Anti p-p collider group

    International Nuclear Information System (INIS)

    While this small group was largely occupied in interacting with other groups, there are some conclusions of general interest. The anti p-p lattice and beam avoidance scheme for a single ring collider, as presented by T. Collins, was accepted as a proof-by-example that a collider could be built with a substantial luminosity. There were no suggestions for improvement, in fact the limitations of this design are not likely to be improved. A production rate of 109 anti p's/sec provides for a total luminosity of 3 x 1033 or 5 x 1032 in each of six interaction regions

  3. 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.

  4. Effects of Egg Shell Membrane Hydrolysates on Anti-Inflammatory, Anti-Wrinkle, Anti-Microbial Activity and Moisture-Protection

    OpenAIRE

    Yoo, JinHee; Park, Kimoon; Yoo, Youngji; Kim, Jongkeun; Yang, Heejin; Shin, Youngjae

    2014-01-01

    This study was conducted to examine the effects of eggshell membrane hydrolysates (ESMH) on the anti-inflammatory, anti-wrinkle, anti-microbial activity, and moisture-protection for cosmetic use. Whole ESMH (before fractionation), and fraction I (>10 kDa), fraction II (3-10 kDa), and fraction III (

  5. 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.

  6. 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.

  7. 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.

  8. Anti-Mullerian hormone and ovarian dysfunction

    NARCIS (Netherlands)

    Broekmans, Frank J.; Visser, Jenny A.; Laven, Joop S. E.; Broer, Simone L.; Themmen, Axel P. N.; Fauser, Bart C.

    2008-01-01

    Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are el

  9. Structural Liberalism and Anti-Bullying Legislation

    Science.gov (United States)

    Vaught, Sabina E.

    2014-01-01

    This article investigates the legal, semantic, and material implications of Massachusetts' anti-bullying law through an analytic framework of structural liberalism. Specifically, this article asks how the law produces categories of fit and unfit subjects of the state through raced and gendered practices of individualism, paternalism,…

  10. 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…

  11. Nanotag luminescent fingerprint anti-counterfeiting technology

    DEFF Research Database (Denmark)

    Radziwon, Michal Jędrzej; Rubahn, Horst-Günter; Johansen, Stefan;

    2012-01-01

    We describe a method to fabricate, transfer and validate via image processing nanofibre- based, unique security marks (“nanotags”) for anti-counterfeiting purposes. Epitaxial surface growth of oligophenylenes on a heated muscovite mica crystal results in a thin film of mutually aligned nanofibres...

  12. Λ(anti Λ) beams at FNAL

    International Nuclear Information System (INIS)

    The discussion of the lambda anti lambda beams involves how to make polarized protons from lambda decay so that experiments on polarization at very high energies may be possible. The aspect studied is the amount of polarization and how to get it

  13. Anti-D: mechanisms of action.

    Science.gov (United States)

    Ware, R E; Zimmerman, S A

    1998-01-01

    Immunoglobulin that recognizes and binds specifically to the erythrocyte D antigen (anti-D globulin, WinRho SDF; Nabi, Boca Raton, FL) has recently been shown to be an effective therapy for many patients with idiopathic thrombocytopenic purpura (ITP). Its mechanisms of action are not completely understood. Intravenous (IV) infusion of anti-D into a D-positive recipient leads to antibody coating of circulating erythrocytes that are cleared primarily by the spleen. This immune-mediated clearance of sensitized erythrocytes occupies the reticuloendothelial system and allows survival of antibody-coated platelets. Based on clinical observations, experimental data, and theoretical calculations, the efficacy of anti-D therapy in ITP depends on several factors that influence the amount of erythrocyte sensitization and the rate of immune-mediated erythrocyte clearance by the spleen. Antibody characteristics, including the antibody concentration, binding affinity, and dissociation constants, may be important, as well as the number of D-antigen binding sites on the erythrocytes. Although the primary mechanism of action of anti-D is believed to be immunologic blockade of Fc receptors (FcR) within the reticuloendothelial system (RES), other immunomodulatory effects are also possible. PMID:9523745

  14. 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…

  15. 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

  16. Renormalized quark-anti-quark free energy

    OpenAIRE

    Zantow, F.; Kaczmarek, O.; Karsch, F.; Petreczky, P.

    2003-01-01

    We present results on the renormalized quark-anti-quark free energy in SU(3) gauge theory at finite temperatures. We discuss results for the singlet, octet and colour averaged free energies and comment on thermal relations which allow to extract separately the potential energy and entropy from the free energy.

  17. SCREENING OF PLANTS FOR ANTI DERMATOPHYTE ACTIVITY

    Directory of Open Access Journals (Sweden)

    V.S. Chauhan, A. Suthar, V. Naik and K. Salkar*

    2012-05-01

    Full Text Available Mycotic infections of skin are caused by dermatophytes. Screening of plants for anti dermatophyte activity was carried out based on the literature search done. Native plants of Maharashtra (India were screened for anti dermatophyte activity. Various plant parts from different regions were collected and then extracted with three different solvents viz. alcohol, hydro-alcohol and aqueous. The obtained extracts were subjected for anti dermatophyte activity using agar-well diffusion technique. Three different concentrations of extract were checked for activity. Two species of dermatophytes, viz. - Trichophyton and Microsporum were used in the screening assay. Out of the twenty-eight plants screened by agar diffusion method, seven were found to be active with different activity profile. Methanol extract was the most active extract. Pterospermum suberifolium, Trachyspermum ammi, Peltaphorum pterocarpum, Ixora coccinia, Persicaria glabra, Terminallia elliptica and Cicca acida showed activity at different concentrations against the two species of dermatophytes. The data obtained can be used for further studying the anti dermatophyte potential of active plants.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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...

  4. Anti-inflammatory Agents: Present and Future.

    NARCIS (Netherlands)

    Dinarello, C.A.

    2010-01-01

    Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory a

  5. Anti-idiotypes against anti-H-2 monoclonal antibodies: structural analysis of the molecules induced by in vivo anti-idiotype treatment.

    OpenAIRE

    Bluestone, J A; Krutzsch, H C; Auchincloss, H.; Cazenave, P A; Kindt, T. J.; Sachs, D. H.

    1982-01-01

    Previous studies have shown that treatment of mice in vivo with xenogeneic anti-idiotype produced against a monoclonal anti-H-2Kk antibody, 11-4.1, leads to the induction of molecules (Id') that inhibit the binding of anti-idiotype to idiotype. To investigate the nature of these Id' molecules, spleens from such anti-idiotype-treated mice were fused with the SP2/0 myeloma to produce monoclonal Id' antibodies. All four monoclonal Id' antibodies were found to react with goat and rabbit anti-11-4...

  6. Anti-Sharing as a Theory of Partnerships and Firms

    OpenAIRE

    Kirstein, Roland; Cooter, Robert D.

    2006-01-01

    Anti-Sharing may improve the efficiency of teams. The Anti-Sharer collects a fixed payment from all team members; he receives the actual output and pays out its value to them. However, if a team members assumes the role of an "internal" Anti-Sharer, he will be unproductive in equilibrium. Hence, internal Anti-Sharing fails to yield the first-best outcome. External Anti-sharing may induce the team members to choose efficient effort. The paper presents possible applications of Anti-Sharing: whi...

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

    Directory of Open Access Journals (Sweden)

    Pham Thi Be Tu

    2015-09-01

    Full Text Available 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; 2,2ʹ-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.

  8. 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.

  9. 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.

  10. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Rajasekaran S

    2012-09-01

    Full Text Available Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1, influenza, picorna, human cytomegalovirus (HCMV and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for various biological activity. Hence a series of benzimidazole derivatives fused with oxadiazole ring system have been synthesized, characterized by UV, IR and 1H NMR spectral data and evaluated for their in vitro and in vivo anti-inflammatory and antioxidant activity.

  11. Kan vericilerde HBsAg, anti-HCV, anti-HIV ve Sifilis seroprevalansı

    OpenAIRE

    Altındiş, Mustafa; Aslan, Savaş; Kalaycı, Raike

    2011-01-01

    Bu çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Kan Merkezi'ne başvuran donörlerde HBsAg, anti-HCV, anti-HIV 1/2 ve RPR seroprevalansının tespiti ve oranların yıllara ve cinsiyete göre dağılımının belirlenmesi amaçlanmıştır. Ocak'2001 ve Aralık'2010 tarihleri arasında Kan Merkezi'ne başvuran 37343 kan donörünün HBsAg, anti-HCV, anti-HIV ½ tarama testleri mikropartikül ELISA (Vitros, Ortho-Clinical Diagnostics) yöntemi ile Ortho-Clinical Diagnostics (HBsAg, HCV 3.jenerasyon, HIV 1/2) ki...

  12. Anti-E Alloimmunization: A Rare Cause of Severe Fetal Hemolytic Disease Resulting in Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    An-Shine Chao

    2009-01-01

    Full Text Available We report a case of severe intrauterine hemolysis caused by sole anti-E alloimmunization. A 36-year-old multipara woman presented with hydrops fetalis at 27 weeks of gestation. She had a history of previous neonatal death. In this pregnancy, she was found to have very high titer of anti-E antibody. Ultrasonography detected marked skin edema, cardiomegaly, hepatosplenomegaly, pleural effusion, ascites, placentomegaly, and polyhydramnios. The Doppler peak systolic velocity in the middle cerebral artery was 0.8 m/s, indicating severe fetal anemia. Multiple intrauterine transfusions for the anemic fetus were administered. However, persistent severe fetal anemia and placentomegaly caused poor neonatal death and mirror syndrome in the mother. Uncommon red blood cell alloimmunization has to be watched for early in any population, especially in a woman with a history of unexplained perinatal loss.

  13. 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.

  14. 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.

  15. 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.

  16. Astemizole: an old anti-histamine as a new promising anti-cancer drug.

    Science.gov (United States)

    García-Quiroz, Janice; Camacho, Javier

    2011-03-01

    Mortality-to-incidence ratio in cancer patients is extremely high, positioning cancer as a major cause of death worldwide. Despite hundreds of clinical trials for anti-cancer drugs that are currently in progress, most clinical trials for novel drug treatments fail to pass Phase I. However, previously developed drugs with novel anti-tumor properties offer a viable and cost-effective alternative to fight cancer. Histamine favors the proliferation of normal and malignant cells. Several anti-histamine drugs, including astemizole, can inhibit tumor cell proliferation. Astemizole has gained enormous interest since it also targets important proteins involved in cancer progression, namely, ether à-go-go 1 (Eag1) and Eag-related gene (Erg) potassium channels. Furthermore, Eag1 is thought to be an important marker and a therapeutic target for several different cancers. Astemizole inhibits Eag1 and Erg channel activity, and in cells expressing the Eag1 channel it decreases tumor cell proliferation in vitro and in vivo. It should be noted that some cardiovascular side effects have been reported for astemizole in a few rare cases. Nevertheless, astemizole stands as a very promising anti-cancer tool because it displays several anti-proliferative mechanisms, may serve as the basis to synthesize new anti-cancer agents, and has been previously administered clinically. In this review we will summarize the main findings relating to histamine and anti-histamines in cancer cell proliferation focusing on astemizole targets (Eag1 and Erg channels), and its anti-cancer effects in vitro and in vivo. We will also describe the side effects of astemizole and discuss proposals to overcome such effects in cancer patients. Finally, we will remark on the relevance of developing novel astemizole-related compounds. PMID:21443504

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

    OpenAIRE

    Gupta Jeetendra Kumar; Sharma Sandeep Kumar; Misra Vimlesh; Patel Kanika

    2011-01-01

    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 ...

  18. 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.)

  19. 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.

  20. 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.

  1. 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.

  2. Sterols from Mytilidae Show Anti-Aging and Neuroprotective Effects via Anti-Oxidative Activity

    Directory of Open Access Journals (Sweden)

    Yujuan Sun

    2014-11-01

    Full Text Available 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.

  3. How to Create an Anti-Aging Skin Care Plan

    Science.gov (United States)

    ... library Find a dermatologist How to create an anti-aging skin care plan Skin care in your 40s ... Years of research supports each of these recommendations. Anti-aging skin care tips Protect your skin from the ...

  4. 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.

  5. Combinatorial Chemotherapeutic Efficacy in non-Hodgkins Lymphoma can be Predicted by a Signaling Model of CD20 Pharmacodynamics

    OpenAIRE

    Harrold, John M.; Straubinger, Robert M.; Mager, Donald E.

    2012-01-01

    Combination chemotherapy represents the standard-of-care for non-Hodgkins lymphoma. However, the development of new therapeutic regimens is empirical and this approach cannot be used prospectively to identify novel or optimal drug combinations. Quantitative system pharmacodynamic models could promote the discovery and development of combination regimens based upon first principles. In this study, we developed a mathematical model that integrates temporal patterns of drug exposure, receptor oc...

  6. 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.)

  7. Redirection of CMV-specific CTL towards B-CLL via CD20-targeted HLA/CMV complexes

    NARCIS (Netherlands)

    R. Mous; P. Savage; E.B.M. Remmerswaal; R.A.W. van Lier; E. Eldering; M.H.J. van Oers

    2006-01-01

    B-cell chronic lymphocytic leukaemia (B-CLL) is a slowly progressing malignancy of CD5(+) B cells, for which at present no curative treatment is available. In our current study, we apply a novel bridging reagent to redirect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) to target B-CLL

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Current anti-doping policy: a critical appraisal

    OpenAIRE

    Mauron Alexandre; Kayser Bengt; Miah Andy

    2007-01-01

    Abstract Background Current anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athlete's health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public. Discussion We review this recent development ...

  13. Democratization System about Anti-corruption and Uphold Integrity

    OpenAIRE

    Peiyong Hou

    2009-01-01

    This article outlines the inevitability of democratization system of anti-corruption and uphold integrity, and analyzes the current situation and causes concerned, thereby introducing the idea of democratization system of anti-corruption and uphold integrity. It Points on relevant solutions of anti-corruption and uphold integrity, intensifying public democracy education and improvement democratization system in anti-corruption and uphold integrity, at the same time, it more try to find out th...

  14. ANTI-PHOSPHATIDYLSERINE ANTIBODIES IN ACUTE MYOCARDIAL INFARCTION

    OpenAIRE

    Abdolreza Sotoodeh Jahromi; Mohammad Shojaei; Mohammad Reza Farjam; Abdolhossien Madani

    2013-01-01

    Acute Myocardial Infarction (AMI) is the combined result of environmental factors and personal predispositions. Many factors play a role in AMI including anti-Phospholipid (aPL) antibodies, that may act in the induction of immunological response leading to the development of AMI. Anti-Phosphatidylserine (PS) antibody is detected in various diseases like rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. The study of anti-PS antibody in AMI might shed l...

  15. 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.

  16. 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.

  17. 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....

  18. 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.

  19. 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

  20. 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...

  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. 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...

  3. 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...

  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-scaling agents in kraft pulping

    Directory of Open Access Journals (Sweden)

    Felissia, F. E.

    2007-05-01

    Full Text Available Scale formation in the digester during kraft pulping represents a great problem in pulp mills. Scaling reduces pulping control and efficiency, increasing energy costs and leading to cleaning breakdowns, with subsequent losses in productivity. The kraft process promotes CaCO3 scaling due to high calcium ion and carbonate concentrations, as well as high alkalinity and temperature levels, which increase the speed with which liquors reach a state of supersaturation. This work examines the action of diethylene triamine penta(methylene phosphonic acid (DTPMPA, either alone or combined with commercial anti-scaling agents, as an inhibitor of calcium carbonate precipitation in the kraft pulping of Pinus taeda. The theoretical amount of calcium deposited in the digester was obtained by mass balance. Soluble calcium was stable throughout cooking when using the phosphonates alone or combined with anti-scaling agents. When adding only DTPMPA, calcium stays in the pulp, rather than forming deposits.

  6. 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.

  7. 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.

  8. Blackfolds in (Anti)-de Sitter Backgrounds

    CERN Document Server

    Armas, Jay

    2010-01-01

    We construct different neutral blackfold solutions in Anti-de Sitter and de Sitter background spacetimes in the limit where the cosmological scale is taken to be much larger than the transverse horizon size. This includes a class of blackfolds with horizons that are products of odd-spheres times a transverse sphere, for which the thermodynamic stability is also studied. Moreover, we exhibit a specific case in which the same blackfold solution can describe different limiting black hole spacetimes therefore illustrating the geometric character of the blackfold approach. Furthermore, we show that the higher-dimensional Kerr-(Anti)-de Sitter black hole allows for ultra-spinning regimes in the relevant limit of large cosmological scale, and demonstrate that this is correctly described by a pancaked blackfold geometry. We also give evidence for the possibility of saturating the rigidity theorem in these backgrounds.

  9. Reengineered tricyclic anti-cancer agents.

    Science.gov (United States)

    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  10. [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.

  11. 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 ...... in distributive justice that it commits us to an implausible anti-statist view of human rights?......, 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...... is anti-statist. On standard liberal interpretations, human rights are such that, logically, they can be violated only by states, not private individuals. An individual who tortures someone commits a moral wrong but does not violate the victim's human rights. For this reason, the crime is less problematic...

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Prospects for Anti-Biofilm Pharmaceuticals

    OpenAIRE

    Stewart, Philip S.

    2015-01-01

    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 dru...

  18. 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.

  19. Dual anti-HIV mechanism of clofarabine

    OpenAIRE

    Daly, Michele B.; Roth, Megan E.; Bonnac, Laurent; Maldonado, José O.; Xie, Jiashu; Clouser, Christine L; Patterson, Steven E.; Kim, Baek; Louis M. Mansky

    2016-01-01

    Background HIV-1 replication kinetics inherently depends on the availability of cellular dNTPs for viral DNA synthesis. In activated CD4+ T cells and other rapidly dividing cells, the concentrations of dNTPs are high and HIV-1 reverse transcription occurs in an efficient manner. In contrast, nondividing cells such as macrophages have lower dNTP pools, which restricts efficient reverse transcription. Clofarabine is an FDA approved ribonucleotide reductase inhibitor, which has shown potent anti...

  20. Artemisinins: pharmacological actions beyond anti-malarial.

    Science.gov (United States)

    Ho, Wanxing Eugene; Peh, Hong Yong; Chan, Tze Khee; Wong, W S Fred

    2014-04-01

    Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from Artemisia annua L. The anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the Plasmodium species. With its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. Artemisinins have been reported to possess robust inhibitory effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis. Artemisinins have been evaluated in animal models of autoimmune diseases, allergic disorders and septic inflammation. The anti-inflammatory effects of artemisinins have been attributed to the inhibition of Toll-like receptors, Syk tyrosine kinase, phospholipase Cγ, PI3K/Akt, MAPK, STAT-1/3/5, NF-κB, Sp1 and Nrf2/ARE signaling pathways. This review provides a comprehensive update on non-malarial use of artemisinins, modes of action of artemisinins in different disease conditions, and drug development of artemisinins beyond anti-malarial. With the concerted efforts in the novel synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is likely that artemisinin drugs will become a major armamentarium combating a variety of human diseases beyond malaria. PMID:24316259

  1. 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.

  2. Anti-thromboembolic strategies in atrial fibrillation.

    Science.gov (United States)

    Cocco, Giuseppe; Amiet, Philpp; Jerie, Paul

    2016-01-01

    Oral anticoagulation (OAC) is highly effective for stroke prevention in high-risk-patients with atrial fibrillation (AF). AF is also a risk for dementia, and effective OAC reduces the risk of dementia. Up to 30% of patients with AF have a coronary artery disease and antiplatelets are used to avoid thrombotic complications. Patients with AF often have an acute coronary syndrome (ACS) and undergo a percutaneous intervention with stent-implantation. These patients require a triple therapy, i.e. the combination of OAC with dual-antiplatelet therapy. It is obvious that OAC may induce bleeding with potentially deleterious effects on mortality. Even the occurrence of minor bleeding is problematic. The review describes available data on used anti-thromboembolic regimens in patients treated with OAC (vitamin K antagonists and non-vitamin K antagonists) who need a triple therapy (i.e. anticoagulation and antiplatelets). Most data are from patients who were treated for an ACS and cannot be directly extrapolated for patients with AF. The impact of used stents and novel P2Y12 antagonist-antiplatelets and duration of triple therapy is discussed. Often some high-risk patients with AF would need anticoagulation but cannot be given this therapy be-cause of excessive bleeding risks or contraindicating comorbidities: in these patients left atrial appendage closure with an occluding device can be used as an alternative to anti-thromboem-bolic therapy. The unavoidable anti-thromboembolic triple therapy carries a strong potential for bleeding events, which increase mortality. We have many data and several recommendations are offered. Nonetheless, we lack solid data on the best anti-thromboembolic regimen in patients with AF who need anticoagulation and antiplatelets. PMID:26779967

  3. MANAJEMEN KURIKULUM DALAM PERSPEKTIF ANTI-RADIKALISME

    Directory of Open Access Journals (Sweden)

    Kisbiyanto Kisbiyanto

    2016-02-01

    Full Text Available The curriculum management in the college of Islamic religious affairs (PTKIN has a strategic role in achieving the vision of the implementation of the higher education especially in Indonesia that has the majority muslim population. PTKIN is responsible in the development of religious harmony and transform the Islamic values that peace and anti-radicalism. The purpose of this research is: (1 designing the Islamic education policy in anti-radicalism perspective at STAIN Kudus; (2 the contents of the curriculum for Islamic education anti-radicalism perspective in STAIN Kudus. This research is used qualitative approach. The data collected by the documentation technique and the triangulation validity. Data analysis by interactive. The results of this research is: (1 Curriculum planning policy Islamic Education department STAIN Kudus is arrangement periodically start from the curriculum 1997, 2003, and 2008. The three periods of curriculum is re-arrange and evaluated by involve the lecturers and experts. This curriculum pattern is called curriculum corelated approach; it is classified from one family courses. This means that the curriculum 2008 is not the curriculum with subject pattern matte curriculum aproach, it emphasizes on courses in a separate settlements. The elective courses is clasified into five groups, namely personality development courses (MPK, scholarly and skills (MKK, courses work (MKB, behavior courses work (MPB, social life courses (MBB. (2 The Islamic education curriculum substance is spread in almost all courses and content on the tendency of the anti-radicalism curriculum and learning, it is a Islamic movements and discourse that give education and peacefull dakwah as a prior, tolerance, humanity, and respect differences as a mercy for the universe.

  4. 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......, I examine whether other virtue-theoretic accounts are able to explain what I call the direction of fit problem...

  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. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Diversity of wheat anti-microbial peptides.

    Science.gov (United States)

    Egorov, Tsezi A; Odintsova, Tatyana I; Pukhalsky, Vitaliy A; Grishin, Eugene V

    2005-11-01

    From seeds of Triticum kiharae Dorof. et Migusch., 24 novel anti-microbial peptides were isolated and characterized by a combination of three-step HPLC (affinity, size-exclusion and reversed-phase) with matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and Edman degradation. Based on sequence similarity and cysteine motifs, partially sequenced peptides were assigned to 7 families: defensins, thionins, lipid-transfer proteins, hevein-like peptides, knottin-like peptides, glycine-rich peptides, and MBP-1 homologs. A novel subfamily of defensins consisting of 6 peptides and a new family of glycine-rich (8 peptides with different repeat motifs) were identified. Three 6-cysteine knottin-like peptides represented by N- and C-terminally truncated variants revealed no sequence homology to any known plant anti-microbial peptides. A new 8-cysteine hevein-like peptide and three 4-cysteine peptides homologous to MBP-1 from maize were isolated. This is the first communication on the occurrence of nearly all families of plant anti-microbial peptides in a single species. PMID:16269343

  12. 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.

  13. Anti-D3's - Singular to the Bitter End

    OpenAIRE

    Iosif Bena; Mariana Grana; Stanislav Kuperstein(Institut de Physique Théorique, CEA Saclay, CNRS URA 2306, F-91191 Gif-sur-Yvette, France); Stefano Massai

    2012-01-01

    We study the full backreaction of anti-D3 branes smeared over the tip of the deformed conifold. Requiring the 5-form flux and warp factor at the tip to be that of anti-D3 branes, we find a simple power counting argument showing that if the three-form fluxes have no IR singularity, they will be necessarily imaginary-anti-self-dual. Hence the only solution with anti-D3 branes at the tip of the conifold that is regular in the IR and the UV is the anti-Klebanov-Strassler solution, and there is no...

  14. Different conceptions of anti-discrimination: an analytical framework

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

    2011-01-01

    In social science and legal studies there is a lack of clarity in the categorisation of different national anti-discrimination policies. To remedy this situation, the article develops an analytical framework for categorising anti-discrimination policies. It suggests that it is useful to distinguish...... between assimilationist, liberal and multiculturalist anti-discrimination policies and demonstrates the usefulness of the analytical framework by analysing the Danish anti-discrimination policy. The categorisation of anti-discrimination policies as assimilationist, liberal or multiculturalist depends...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

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

    OpenAIRE

    Pham Thi Be Tu; Shinkichi Tawata

    2015-01-01

    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); 2,2ʹ-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...

  1. 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.

  2. Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

    OpenAIRE

    Hirose, Mai; Ando, Taishi; Shofiqur, Rahman; Umeda, Kouji; Kodama, Yoshikatsu; Van Nguyen, Sa; Goto, Tsuyoshi; Shimada, Masaya; Nagaoka, Satoshi

    2013-01-01

    Background There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. Methods We determined the inhibitory action of Anti-lipase IgY on lipas...

  3. 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

  4. 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.

  5. The (Sea)Quest to map anti-up and anti-down quarks

    Science.gov (United States)

    Diefenthaler, Markus

    2015-10-01

    The SeaQuest experiment at Fermilab continues a series of Drell-Yan measurements to explore the antiquark content of the nucleon and to study the modifications to nucleon structure when the nucleon is embedded into a nuclei. To extend existing measurements to larger values of Bjorken-x, a 120 GeV proton beam extracted from Fermilab's Main Injector is used, resulting in 50 times more luminosity than previous experiments and enabling access to values of x up to 0.9. One of the key physics goals of the SeaQuest collaboration is the exploration of the origin of the intrinsic nucleon sea. The scale dependence observed in high-energy scattering experiments reflects the quantum fluctuations predicted by QCD. A sea of virtual gluons arises in the nucleon; these gluons radiate other gluons or pairs of quarks and antiquarks. Gluon splitting, e.g. into an u anti-u quark pair or a d anti-d quark pair, is a perturbative QCD process and flavor symmetric. However, there is clear experimental evidence that the nucleon sea is not flavor symmetric. The distributions for anti-d quarks and anti-u quarks differ by up to 50% and suggest a substantial role of non-perturbative QCD processes in the creation of the nucleon sea. Measuring the ratio of the anti-d quark and anti-u quark distributions with high accuracy and within a large x-range is the key measurement of the SeaQuest experiment. The SeaQuest results will help to identify effective theories that can describe the intrinsic nucleon sea and help to explore its origin. On behalf of the SeaQuest Collaboration.

  6. 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

  7. 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.

  8. 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.

  9. Book review: anti-porn: the resurgence of anti-pornography feminism

    OpenAIRE

    Spoto, Stephanie

    2013-01-01

    Countering the ongoing ‘pornification’ of Western culture and society, with lads’ mags on the middle shelf and lap-dancing clubs in residential areas, anti-porn movements are re-emerging among a new generation of feminist activists worldwide. This guide to the problems with porn starts with a history of modern pro and anti political stances before examining the ways in which the new arguments and campaigns around pornography are articulated, deployed and received. If you’re looking for a hist...

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

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Hansen, Jørgen Drud

    ’ 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...... 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...

  11. 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

  12. 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.

  13. Wie rassistisch sind Anti-Rassist/-innen? How Racist are Anti-Racists?

    OpenAIRE

    Ilka Borchardt

    2003-01-01

    Anja Weiß beschäftigt sich mit einem all zu oft emotional behandelten Thema: dem Rassismus anti-rassistisch Engagierter. Sie versucht die häufig widersprüchlichen Auseinandersetzungen und Emotionen um Rassismus und Rassismus-Vorwürfe versucht Weiß kreativ im Forschungsprozess zu verwenden.Anja Weiß does a very thorough and committed job of presenting a difficult topic, investigating the racism of those who self-identify as anti-racist activists. This topic may often seem paradoxical, and is u...

  14. New observables in the decay mode anti-B --> anti-K*0 l+ l-

    OpenAIRE

    Egede, U.; Hurth, T.; Matias, J.; Ramon, M.; Reece, W.(CERN, European Organization for Nuclear Research, Geneva, Switzerland)

    2008-01-01

    We discuss the large set of observables available from the angular distributions of the decay anti-B --> anti-K*0 l+ l-. We present a NLO analysis of all observables based on the QCD factorization approach in the low-dilepton mass region and an estimate of \\Lambda/m_b corrections. Moreover, we discuss their sensitivity to new physics. We explore the experimental sensitivities at LHCb (10 fb^-1) and Super-LHCb (100 fb^-1) based on a full-angular fit method and explore the sensitivity to right ...

  15. Delayed Serological Transfusion Reaction After Platelet Transfusion Due to Anti-e.

    Science.gov (United States)

    Sachan, Deepti; Kumar, Aswin; Jothimani, Dinesh; Rela, Mohamed

    2016-06-01

    Delayed serological transfusion reaction (DSTR) is defined as absence of clinical signs of hemolysis and demonstration of new, clinically-significant antibodies against red blood cells after a transfusion, by either positive direct antiglobulin test or positive antibody screen with newly identified RBC alloantibody. Various delayed hemolytic transfusion reaction cases are reported after red cell transfusions. However, the incidence of DSTR after platelet transfusion due to non-Rh(D) antibodies is not much documented. We report here a case of DSTR due to anti-e Rh antibody in a multiply red cell alloimmunized female patient after single donor platelets transfusion. PMID:27408414

  16. 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

  17. 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.].

  18. 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...

  19. A Tale of Two Anti-Americanisms

    OpenAIRE

    Pierre Guerlain

    2007-01-01

    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 Wallerstein What 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 ag...

  20. 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.

  1. Quantum Anti-de Sitter Space

    OpenAIRE

    Chang, Zhe

    1999-01-01

    The quantum Anti-de Sitter (AdS) group and quantum AdS space is discussed. Ways of getting the quantum AdS group from real forms of quantum orthogonal group are presented. Differential calculus on the quantum AdS space are also introduced. In particular, reality of differential calculus are given. We set up explicit relationships between quantum group and quantum algebra, which can be refereed as the quantum counterpart of the classical exponential. By this way, quantum AdS algebra is deduced...

  2. Recent Developments in Anti-Tank Ammunition

    Directory of Open Access Journals (Sweden)

    N. S. Venkatesan

    1985-04-01

    Full Text Available Every advance in anti-tank ammunition has been matched by advances in armour material or vice-versa. This applies both to kinetic energy and chemicai energy type of ammunition. Today the kinetic energy ammunition appears to have an upper hand over armour. In t his paper, a brief survey of the modern FSAPDS ammunition, its design aspects and its material technology is made.The capabilities of HEAT type of ammunition are also discussed and the likely trends in ammunition technology are indicated. Some futuristic developments in the field of propulsion are briefly mentioned.

  3. Anti-noise Protective Agents in Tractors

    OpenAIRE

    Hudec, Miroslav

    2010-01-01

    The aim of my bachelor´s thesis is anti-noise protective agents in tractors. In this work I focused on influence of wanted and unwanted noise to humans and the results of it. In other part I concerned with simple calculation of noise, each sources´ vibration and sound transmission of solids. These calculations are very complicated and complex but for my purpose I simplified them and used only the basic ones. The next procedure is to clear out the noise by constructional alterations, which are...

  4. 反英雄%Anti-hero

    Institute of Scientific and Technical Information of China (English)

    王岚

    2005-01-01

    概说 “反英雄”(anti-hero)是与“英雄”相对立的一个概念,是电影、戏剧或小说中的一种角色类型。作者通过这类人物的命运变化对传统价值观念进行“证伪”,标志着个人主义思想的张扬、传统道德价值体系的衰微和人们对理想信念的质疑。

  5. 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

  6. 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

  7. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2 anti-oxidative stress/anti-inflammatory pathways

    Directory of Open Access Journals (Sweden)

    Wu Qing

    2010-10-01

    Full Text Available Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2-like 2 (Nrf2 or NFE2L2-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE, a critical regulatory element in the promoter region of genes encoding cellular phase II detoxifying and anti-oxidative stress enzymes. The studies on the chemopreventive effects of ginseng or its components/products showed that Nrf2 could also be a target for ginseng's actions. A number of papers also demonstrated the anti-inflammatory effects of ginseng. Targeting Nrf2 pathway is a novel approach to the investigation of ginseng's cancer chemopreventive actions, including some oxidative stress and inflammatory conditions responsible for the initiation, promotion and progression of carcinogenesis.

  8. [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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. EVALUATION OF ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF FLOATING MICROSPHERES OF HERBAL DRUG

    Directory of Open Access Journals (Sweden)

    Kapil Kumar

    2012-01-01

    Full Text Available The aim of the present studies was to prepare and evaluate floating microspheres of curcumin for anti-inflammatory and anti-arthritic effect. Floating microsphere were prepared using hydroxyl propyl methylcellulose (HPMC, ethyl cellulose (EC, polyvinyl pyrrolidone K30 (PVPK30, eudragit RS 100 polymer in different ratio and dichloromethane and heavy liquid paraffin as solvent by emulsion solvent diffusion method. The floating microspheres were evaluated for flow properties based on parameters such as angle of repose and compressibility index, as well as for various other physicochemical properties including particle size, incorporation efficiency, in-vitro floatability, and in-vitro drug release. The shape and surface morphology of the microspheres were characterised by scanning electron microscopy. Scanning electron microscopy showed pores on the surface and interior of the microspheres. Anti-inflammatory, anti-arthritic effect of formulation C4 and E1 were compared with standard market product Indomethacin. The effect of formulation C4 and E1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud’s adjuvant (CFA induced arthritis in rats. Further histopathological and radiographic evaluation was performed. It may be concluded that Curcumin microspheres would be promising drug delivery system for oral administration of Curcumin to sustained the drug release. Incorporation of herbal drugs in novel drug delivery system may lead to an excellent result.

  14. Heparin alters viral serpin, serp-1, anti-thrombolytic activity to anti-thrombotic activity.

    Science.gov (United States)

    Li, Xing; Schneider, Heather; Peters, Andrew; Macaulay, Colin; King, Elaine; Sun, Yunming; Liu, Liying; Dai, Erbin; Davids, Jennifer A; McFadden, Grant; Lucas, Alexandra

    2008-01-01

    Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways. PMID:18949070

  15. 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. PMID:25680890

  16. A possible anti-proliferative and anti-metastatic effect of irradiated riboflavin in solid tumours

    NARCIS (Netherlands)

    de Souza Queiroz, Karla Cristiana; Zambuzzi, Willian Fernando; de Souza, Ana Carolina Santos; da Silva, Rodrigo Augusto; Machado, Daisy; Justo, Giselle Zenker; Carvalho, Hernandes F.; Peppelenbosch, Maikel P.; Ferreira, Carmen Verissima

    2007-01-01

    Riboflavin is a potent photosensitizer as well as part of the vitamin B complex. Recently we demonstrated that the products generated by irradiation of riboflavin have potential as anti-leukaemic therapy. The possible action, however, of the riboflavin photoproducts in solid cancers has not been add

  17. 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.

  18. 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.

  19. 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.

  20. Anti-diarrheal constituents of Alpinia oxyphylla.

    Science.gov (United States)

    Zhang, Junqing; Wang, Sheng; Li, Yonghui; Xu, Peng; Chen, Feng; Tan, Yinfeng; Duan, Jinao

    2013-09-01

    Isolation, screening and in vivo assays have been used for evaluating anti-diarrhea bioactive of Alpinia oxyphylla. Preliminary experimental results showed that 95% ethanol extract and 90% ethanol elution significantly extended the onset time of diarrhea and reduced the wet feces proportion, however 50% ethanol election had no effect on diarrhea. Chemical analysis results displayed that Nootkatone, Tectochrysin and yakuchinone A may be bioactive ingredients for curing diarrhea. Duodenum in vitro experiment showed that Tectochrysin 50, 100 μM reduces carbachol-induced contraction, while yakuchinone A and Nootkatone had no effect. Bioinformatic computational method as molecular docking has been complementary to experimentally work to explore the potential mechanism. The study of pathogenesis of diarrhea in humans and animal models suggested that Na(+)/H(+) exchanger3 (NHE3) and aquaporin4 (AQP4) are causative agents of diarrhea. The analysis was done on the basis of scoring and binding ability and the docking analysis showed that Tectochrysin has maximum potential against NHE3 (PDB ID: 2OCS) and AQP4 (PDB ID: 3GD8). Tectochrysin indicated minimum energy score and the highest number of interactions with active site residues. These results suggested that A. oxyphylla might exhibit its anti-diarrhea effect partially by affecting the proteins of NHE3 and AQP4 with its active ingredient Tectochrysin. PMID:23583435

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. A Study of Anti Beta-2 Glycoprotein I and Anti-Prothrombin Antibodies in Patients with Unexplained Recurrent Pregnancy Losses.

    Science.gov (United States)

    Singh, Angad; Nangia, Anita; Sharma, Sunita; Puri, Manju

    2016-06-01

    To compare the levels of IgG and IgM anti beta-2 glycoprotein I antibodies and IgG and IgM anti prothrombin antibodies among women with unexplained recurrent pregnancy losses and women with at least 2 live issues. To compare the prevalence of newer anti beta-2 glycoprotein I & anti prothrombin antibodies with conventional Lupus anticoagulant & anticardiolipin antibodies. 50 women with recurrent pregnancy losses & 50 matched controls were evaluated for the presence of: Lupus anticoagulant-screened by LA sensitive aPTT& DRVV and confirmatory Staclot Assay. ELISA kits were used for detecting IgG & IgM anticardiolipin, anti beta-2 glycoprotein I & anti prothrombin antibodies. 11/50 (22 %) women in study group and none in control group had circulating antiphospholipid antibodies. 2 cases (4 %) had lupus anticoagulant. 1 case (2 %) had anticardiolipin antibody & 6 cases (12 %) were positive for anti beta-2 Glycoprotein I antibody (p value = 0.027). 3 cases (6 %) had anti prothrombin antibody. All were mutually exclusive except for one. Women with recurrent pregnancy losses should be tested for anti beta-2 Glycoprotein I antibodies & anti prothrombin antibodies in addition to conventional lupus anticoagulant and anticardiolipin antibodies. This approach can decrease the incidence of SNAP (seronegative antiphospholipid syndrome) cases while establishing the true prevalence of antiphospholipid syndrome. PMID:27065583

  7. 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.

  8. Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells

    Science.gov (United States)

    Kilgore, Joshua; Jackson, Amanda L; Clark, Leslie H; Guo, Hui; Zhang, Lu; Jones, Hannah M; Gilliam, Timothy P; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

    2016-01-01

    Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines. Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting. Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines. Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation. PMID:27398153

  9. [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.

  10. 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.

  11. 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.

  12. Test Production of Anti-Corrosive Paint in Laboratory Scale

    International Nuclear Information System (INIS)

    The main purpose of this project is to produce the anti-corrosive paint in laboratory scale. In these experiments, local raw materials, natural resin (shellac), pine oil, turpentine and ethyl alcohol wer applied basically. Laboratory trials were undrtaken to determine the suitablity of raw materials ane their composition for anti-corrosive paint manufacture.The results obtained show that the anti-corrosive paint from experiment No.(30) is suitable for steel plate and this is also considered commercially economics

  13. Topical anti-inflammatory activity of yacon leaf extracts

    OpenAIRE

    Rejane B. Oliveira; Daniela A. Chagas-Paula; Adriana Secatto; Thaís H. Gasparoto; Faccioli, Lúcia H.; Campanelli, Ana P.; Fernando B. Da Costa

    2013-01-01

    Smallanthus sonchifolius (Poepp.) H. Rob. , Asteraceae, known as yacon, is an herb that is traditionally used for the treatment of diabetes in folk medicine. However, recent studies have demonstrated that this plant has other interesting properties such as anti-microbial and anti-inflammatory actions. Thus, the purpose of this study was to evaluate the topical anti-inflammatory property of different extracts prepared from yacon leaves and analyze the role of different chemical classes in this...

  14. Lectins with Anti-HIV Activity: A Review

    OpenAIRE

    Ouafae Akkouh; Tzi Bun Ng; Senjam Sunil Singh; Cuiming Yin; Xiuli Dan; Yau Sang Chan; Wenliang Pan; Randy Chi Fai Cheung

    2015-01-01

    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 al...

  15. 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.

  16. Paroxetine versus other anti-depressive agents for depression

    OpenAIRE

    Cipriani, Andrea; Furukawa, Toshi A.; Veronese, Antonio; Watanabe, Norio; Churchill, Rachel; McGuire, Hugh; Barbui, Corrado

    2007-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of major depressive disorder.To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents.

  17. 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.

  18. PHYTOCHEMICAL SCREENING AND ANTI MICROBIAL STUDIES OF HEMIDESMUS INDICUS

    Directory of Open Access Journals (Sweden)

    Jayasimha Rayalu Daddam

    2015-10-01

    Full Text Available Many forms of alternative medicines were available for those who cannot be helped by conventional medicine. Ayurvedha and Herbal medicine were two important forms of alternative medicine that was widely available in India. This work was mainly concerned with the identification of the therapeutic properties of Hemidesmus indicus. The ethanolic extract of hemidesmus indicus root was used for its anti oxidant and antimicrobial activity. Hemidesmus indicus root extract has very well anti oxidant and anti microbial activity. The ethanolic extract of Hemidesmus indicus was checked for anti microbial activity against pathogenic bacteria such as staphylococcus aures, pseudomonas aeruginosa andfungi Aspergillus niger.

  19. 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.

  20. 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. PMID:25121157

  1. 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.

  2. 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

  3. 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.

  4. Yeast killer toxin-like anti-idiotypic antibodies.

    OpenAIRE

    POLONELLI, L.; Morace, G

    1988-01-01

    Anti-idiotypic antibodies (anti-Ids) were raised in a rabbit against a murine monoclonal antibody (MAb) neutralizing the yeast killer toxin produced by a strain of Pichia (Hansenula) anomala. In an immunodiffusion test, the anti-Ids produced in the rabbit recognized the antigen-binding site of the MAb used as the immunogen (KT4) but not that of another heterologous MAb. The absence of any significant cross-reactivity among the anti-Ids raised in a rabbit for a heterologous MAb suggested that ...

  5. 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.

  6. Anti-Dumping Procedures In The Eurasec Customs Union

    OpenAIRE

    Alexander A. Yalbulganov

    2014-01-01

    The creation of the EurAsEC Customs Union and Russia’s ascension into the WTO has led to a radical change in Russia’s anti-dumping legislation. Anti-dumping regulation ceased to fall under national jurisdiction and was transferred to the Eurasian Economic Commission, a supranational regulator. This article analyzes the new anti-dumping legislation of the EurAsEC Customs Union, anti-dumping procedures, their principles, participants, and main stages, as well as the legal treatment of informati...

  7. Anti-arthritic and immunosuppressive activities of substituted triterpenoidal candidates.

    Science.gov (United States)

    Alanazi, Amer M; Al-Omar, Mohamed A; Abdulla, Mohamed M; Amr, Abd El-Galil E

    2013-07-01

    We herein report the anti-arthritic and immunosuppressive activities of some synthesized substituted terpenoidal structure. Forty-four triterpenoid derivatives 1-21 containing a carboxylic, ester, amide and ketone groups attached to a triterpene moiety were conveniently synthesized and screened for their anti-arthritic and immunosuppressive activities. Synthetic triterpenoidal structures linked to a different function groups seem to be a promising approach in the search for novel leads for potent anti-arthritic and immunosuppressive agents. The detailed synthetic pathways of obtained compounds and anti-arthritic and immunosuppressive activities were reported. PMID:23603083

  8. 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.

  9. 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.

  10. Anti-scorpion venom activity of Andrographis paniculata: A combined and comparative study with anti-scorpion serum in mice

    OpenAIRE

    Ranjana S Kale; Satish E Bahekar; Nagpure, Shailesh R.; Salwe, Kartik J.

    2013-01-01

    Objectives: The objective of this study is to evaluate the anti-scorpion venom (ASV) property of Andrographis paniculata in comparison with anti-redscorpion venom serum and this study aimed to determine its combined effect with anti-redscorpion venom serum. Materials and Methods: Ethanolic extract of the plant AP was obtained using soxhlet apparatus. Swiss albino mice weighing 20-30g were used. Lyophilized venom sample of Mesobuthus tamulus and Lyophilized monovalent enzyme refined immuno...

  11. Anti-biofilm and anti-adherence activity of Glm-U inhibitors

    Directory of Open Access Journals (Sweden)

    Ethel Suman

    2011-01-01

    Full Text Available Background: Intravascular catheters and urinary catheters are an important source of hospital-acquired infections. Many microorganisms colonize indwelling catheters, including central venous catheters (CVCs forming biofilms and cause infections that are difficult to treat. Although various methods have been employed to reduce biofilms, enzymes involved in bacterial cell wall synthesis could provide novel targets for the development of anti-biofilm agents. N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU is an essential enzyme in aminosugars metabolism and catalyzes the formation of uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc, an important precursor in the peptidoglycan and lipopolysaccharide biosynthesis of Gram-positive and Gram-negative bacteria. Previous study has been conducted on the anti-biofilm effect of GlmU inhibitors such as N-ethyl maleimide (NEM and NEM analogs along with a cationic polypeptide protamine sulfate (PS, which enhanced its anti-biofilm activity. AIM: The present study aimed at finding the effect of sub-inhibitory concentrations of N-ethyl maleimide (NEM and protamine sulfate (PS on the biofilms produced by Pseudomonas aeruginosa and Enterococcus spp. isolated from cases of catheter-associated UTI as well as Klebsiella pneumoniae and Staphylococcus aureus isolated from cases of catheter-related bloodstream infections (CRBSI. Materials and Methods: In order to enhance the activity of NEM and to develop a broad-spectrum anti-microbial composition, NEM (50 μg/ml was combined with protamine sulfate (50 μg/ml and tested for anti-biofilm activity using a standard quantitative biofilm assay method. Results and Conclusion: It was observed that NEM had no effect on the biofilm produced by Pseudomonas aeruginosa as well as by Enterococcus spp. NEM also caused a significant decrease in biofilm production by Staphylococcus aureus while it had no effect on the biofilm produced by Klebsiella pneumoniae. There was a

  12. 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.

  13. Ashless Anti- Wear Additives for Motor Oils

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Ashless anti- wear (AW) additives containing phosphorus can be used as partial or complete replacement of zinc dithiodialkylphosphate (ZDDP). In oils with low sulfated ash content (< 1.0%), this approach will allow a significant reduction of ash content and/or provide the formulator with more flexibility to use additional metallic detergents. Over the past 70 years or so, ZDDP has proven to be a very effective engine oil additive by helping to reduct oxidation, wear, and corrosion in service. In this paper, we will compare ZDDP- based lubricants with lubricants base on ashless, P- containing additive systems; we will describe the ashless chemistry investigated and discuss its contribution to wear performance in modem, low- SAPS (sulfated ash, phosphorus & sulfur) engine oils in various bench, rig and engine tests; we will also report on some work done to evaluate AW additive compatibility with modern three- way exhaust gas catalysts (TWC).

  14. Review of Anti-Inflammatory Herbal Medicines.

    Science.gov (United States)

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    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. PMID:27247570

  15. [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).

  16. Advances in anti-epileptic drug testing.

    Science.gov (United States)

    Krasowski, Matthew D; McMillin, Gwendolyn A

    2014-09-25

    In the past twenty-one years, 17 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are clobazam, ezogabine (retigabine), eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. Therapeutic drug monitoring is often used in the clinical dosing of the newer anti-epileptic drugs. The drugs with the best justifications for drug monitoring are lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and zonisamide. Perampanel, stiripentol and tiagabine are strongly bound to serum proteins and are candidates for monitoring of the free drug fractions. Alternative specimens for therapeutic drug monitoring are saliva and dried blood spots. Therapeutic drug monitoring of the new antiepileptic drugs is discussed here for managing patients with epilepsy. PMID:24925169

  17. 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.

  18. 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.

  19. Anti-fungal activity of irradiated chitosan

    International Nuclear Information System (INIS)

    Anti-fungal activity of chitosan induced by irradiation has been investigated. Commercial chitosan samples of 8B (80% deacetylation) and l0B (99% deacetylation) were irradiated by γ-ray in dry condition. Highly deacethylated chitosan (10B) at low dose irradiation (75 kGy) was effective for inhibition of fungal growth. The sensitivities of Exobasidium vexans, Septoria chrysanthemum and Gibberella fujikuroi for the irradiated chitosan were different and the necessary concentrations of chitosan were 550, 350 and 250 μg/ml, respectively. For the plant growth, low deacethylation (chitosan 8B) and high dose (500 kGy) was effective and the growth of chrysanthemum was promoted by spraying the irradiated chitosan. (author)

  20. Artemisinin anti-malarial drugs in China.

    Science.gov (United States)

    Guo, Zongru

    2016-03-01

    Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. PMID:27006895

  1. 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.

  2. Anti-TNFs: Originators and Biosimilars.

    Science.gov (United States)

    Mantzaris, Gerassimos J

    2016-01-01

    In the last 20 years, the advent of anti-tumor necrosis factor alpha (TNFα) biologics has revolutionized the treatment of patients with inflammatory bowel disease (IBD) but the cost of biologic therapy now constitutes a large proportion of all healthcare expenditures. Patent expiration has sparked the healthcare industry's interest in the production of biosimilar (BS) versions of first generation biologics (originators [ORGs]) for market sharing. Having no access to the production line of the ORG, the sponsor of a BS needs to develop his own manufacturing process to produce a highly similar version of the reference product. Similarity in structure, physicochemical properties, biologic activity, efficacy and safety must be demonstrated by a comprehensive comparability exercise that includes the most sensitive in vitro tests, models and clinical condition with pre-defined equivalence margins. Extrapolation of indications, inter-changeability and automatic substitution between BS and ORG depend on a legal framework that varies between different agencies. It is not, therefore, unexpected that marketing authorization by the European Medicines Agency and other regulatory agencies (but not Health Canada) of CT-P13 (Remsima/Inflectra) as infliximab (Remicade) BSs for IBD by indication extrapolation has led to stormy discussions in the IBD community and beyond regarding the scientific adequacy of this decision. However, as we now have to live with BSs, we hope that the impeding automatic substitution in association with post-marketing pharmacovigilance, full traceability, registries and new studies will settle the controversy and will increase the confidence of physicians and patients. A universally adopted legal framework should be implemented because, as expected, the non-anti-TNFα BSs will be soon on the stage. PMID:26983015

  3. 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.

  4. CF102 an A3 Adenosine Receptor Agonist Mediates Anti-Tumor and Anti-Inflammatory Effects in the Liver

    OpenAIRE

    Cohen, S.; Stemmer, S M; ZOZULYA, G.; Ochaion, A.; PATOKA, R.; Barer, F.; BAR-YEHUDA, S.; RATH-WOLFSON, L.; Jacobson, K. A.; Fishman, P

    2011-01-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is a member of the adenosine receptor family. Selective agonists at the A3AR, such as CF101 and CF102 were found to induce anti-inflammatory and anti-cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti-inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti-cancer effect of CF102 was examine...

  5. 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.

  6. Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies.

    Science.gov (United States)

    Cozzani, Emanuele; Christana, Konstantina; Mastrogiacomo, Alessandro; Rampini, Paolo; Drosera, Massimo; Casu, Massimo; Murialdo, Giovanni; Parodi, Aurora

    2007-01-01

    Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating lesions in the folds and mouth and by the presence of autoantibodies against desmoglein 3. We describe two Caucasian patients with pemphigus vegetans, one of them presented antibodies to desmoglein 3 and 1 and the other one to desmoglein 3. Both patients also had circulating antibodies against a 190 kDa protein co-migrating with periplakin. Anti-periplakin reactivity is usually detected in paraneoplastic pemphigus, while it has never been reported in pemphigus vegetans. Our observation enlarges the spectrum of autoantibodies which may be associated with pemphigus vegetans. However, the pathophysiological significance of anti-periplakin reactivity in this pemphigus variant remains to be determined. PMID:17951135

  7. Wie rassistisch sind Anti-Rassist/-innen? How Racist are Anti-Racists?

    Directory of Open Access Journals (Sweden)

    Ilka Borchardt

    2003-03-01

    Full Text Available Anja Weiß beschäftigt sich mit einem all zu oft emotional behandelten Thema: dem Rassismus anti-rassistisch Engagierter. Sie versucht die häufig widersprüchlichen Auseinandersetzungen und Emotionen um Rassismus und Rassismus-Vorwürfe versucht Weiß kreativ im Forschungsprozess zu verwenden.Anja Weiß does a very thorough and committed job of presenting a difficult topic, investigating the racism of those who self-identify as anti-racist activists. This topic may often seem paradoxical, and is usually dealt with in a very emotional way. Weiß attempts to recognise all the contradictions and emotions involved, and to creatively integrate them into her research.

  8. 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

    2000-06-01

    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. PMID:10866389

  9. Anti-Oxidant and Anti-Inflammatory Activities of Inonotus obliquus and Germinated Brown Rice Extracts

    OpenAIRE

    Beong Ou Lim; Jeong Eun Jo; Da Hye Kim; Trishna Debnath; Sa Ra Park

    2013-01-01

    Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed...

  10. Evaluation of Calendula officinalis as an anti-plaque and anti-gingivitis agent

    OpenAIRE

    Mayur Sudhakar Khairnar; Babita Pawar; Pramod Parashram Marawar; Ameet Mani

    2013-01-01

    Background: Calendula officinalis (C. officinalis), commonly known as pot marigold, is a medicinal herb with excellent antimicrobial, wound healing, and anti-inflammatory activity. Aim: To evaluate the efficacy of C. officinalis in reducing dental plaque and gingival inflammation. Materials and Methods: Two hundred and forty patients within the age group of 20-40 years were enrolled in this study with their informed consent. Patients having gingivitis (probing depth (PD) ≤3 mm), with a compla...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

    Science.gov (United States)

    Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

    2005-01-01

    As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects. PMID:15635170

  18. 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.

  19. Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

    Science.gov (United States)

    Fonsêca, Diogo V; Salgado, Paula R R; Aragão Neto, Humberto de C; Golzio, Adriana M F O; Caldas Filho, Marcelo R D; Melo, Cynthia G F; Leite, Fagner C; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Barbosa Filho, José M; Almeida, Reinaldo N

    2016-09-01

    Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.

  20. 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.

  1. Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

    Science.gov (United States)

    Fonsêca, Diogo V; Salgado, Paula R R; Aragão Neto, Humberto de C; Golzio, Adriana M F O; Caldas Filho, Marcelo R D; Melo, Cynthia G F; Leite, Fagner C; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Barbosa Filho, José M; Almeida, Reinaldo N

    2016-09-01

    Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time. PMID:27355133

  2. Role of anti-thrombotic therapy for recurrent pregnancy loss due to anti-phospholipid syndrome

    International Nuclear Information System (INIS)

    Background: Recurrent pregnancy loss is a major health problem effecting 1 to 2% of women of reproductive age. Its causes range from chromosomal abnormalities to endocrinological factors and thrombophilia related factors. Treating thrombophilia s especially anti phospholipid syndrome with low dose aspirin and low molecular weight heparin improves foetal outcome. This study will add local data to already existing knowledge. Method: Sixty selected patients from gynaecology OPD of Aero Hospital with clinical and/or serological findings of anti phospholipid syndrome from February 2009 to January 2011 were given aspirin 75 mg once daily and enoxaparine 40 mg subcutaneously once daily from 6 - 8 weeks to 35 and 37 weeks respectively. Results : Ninety-three percent of patients achieved live birth. Out of these 75% patients delivered at term and 18% had preterm delivered. Four (7%) had early pregnancy loss and only one had early neonatal death due to extreme prematurity. None of patients experienced any major hemorrhagic complications . Conclusion: Use of low dose aspirin and low molecular weight heparin is safe in pregnancy and improve foetal outcome in patients with recurrent pregnancy loss due to anti phospholipids syndrome. (author)

  3. 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.

  4. Antioxidant, Anti-Tyrosinase and Anti-Inflammatory Activities of Oil Production Residues from Camellia tenuifloria

    Directory of Open Access Journals (Sweden)

    Shu-Yuan Chiou

    2015-12-01

    Full Text Available Camellia tenuifloria is an indigenous Camellia species used for the production of camellia oil in Taiwan. This study investigated for the first time the potential antioxidant, anti-tyrosinase and anti-inflammatory activities of oil production byproducts, specifically those of the fruit shell, seed shell, and seed pomace from C. tenuifloria. It was found that the crude ethanol extract of the seed shell had the strongest DPPH scavenging and mushroom tyrosinase inhibitory activities, followed by the fruit shell, while seed pomace was the weakest. The IC50 values of crude extracts and fractions on monophenolase were smaller than diphenolase. The phenolic-rich methanol fraction of seed shell (SM reduced nitric oxide (NO production, and inducible nitric oxide synthase (iNOS expression in lipopolysaccharide (LPS-stimulated RAW 264.7 cells. It also repressed the expression of IL-1β, and secretion of prostaglandin E2 (PGE2 and IL-6 in response to LPS. SM strongly stimulated heme oxygenase 1 (HO-1 expression and addition of zinc protoporphyrin (ZnPP, a HO-1 competitive inhibitor, reversed the inhibition of NO production, indicating the involvement of HO-1 in its anti-inflammatory activity. The effects observed in this study provide evidence for the reuse of residues from C. tenuifloria in the food additive, medicine and cosmetic industries.

  5. Cattle tick-associated bacteria exert anti-biofilm and anti-Tritrichomonas foetus activities.

    Science.gov (United States)

    Zimmer, K R; Seixas, A; Conceição, J M; Zvoboda, D A; Barros, M P; Tasca, T; Macedo, A J; Termignoni, C

    2013-05-31

    Research on microbiota in cattle tick and the evaluation of its activity against other microorganisms can contribute to identify new molecules potentially useful to control infections caused by bacteria and protozoa. Biofilms pose increasing problems worldwide, mainly due to their resistance to antimicrobial therapies and host immune response. In this study we investigate the ability Rhipicephalus (Boophilus) microplus-associated bacteria may exhibit to produce anti-biofilm and trichomonicidal compounds. Gut, ovary, salivary glands, and Gené organ were collected from engorged R. microplus female. Homogenates of each tissue were inoculated onto 15 distinct culture media. Anti-biofilm and trichomonicidal activities were analyzed by culturing each bacterium isolated in a liquid medium. Results showed that R. microplus cattle tick microflora varies for different tissues. Bacteria belonging to different genera (Aeromonas, Bacillus, Brevibacillus, Castelaniella, Comamonas, Kocuria, and Microbacterium) were identified. Interestingly, all bacterial species found displayed pronounced activity against Staphylococcus epidermidis and Pseudomonas aeruginosa biofilms, and also against the cattle pathogen Tritrichomonas foetus, confirming the hypothesis that cattle tick could be a source of bacteria active against pathogens. This is the first study showing that bacteria isolated from a tick exert anti-biofilm and trichomonicidal activities. PMID:23434012

  6. Evaluation of Anti-Nociceptive and Anti-Inflammatory Activities of a Heterofucan from Dictyota menstrualis

    Directory of Open Access Journals (Sweden)

    Helena Bonciani Nader

    2013-08-01

    Full Text Available 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.

  7. Recent Progress in Anti-Obesity and Anti-Diabetes Effect of Berries.

    Science.gov (United States)

    Tsuda, Takanori

    2016-01-01

    Berries are rich in polyphenols such as anthocyanins. Various favorable functions of berries cannot be explained by their anti-oxidant properties, and thus, berries are now receiving great interest as food ingredients with "beyond antioxidant" functions. In this review, we discuss the potential health benefits of anthocyanin-rich berries, with a focus on prevention and treatment of obesity and diabetes. To better understand the physiological functionality of berries, the exact molecular mechanism of their anti-obesity and anti-diabetes effect should be clarified. Additionally, the relationship of metabolites and degradation products with health benefits derived from anthocyanins needs to be elucidated. The preventive effects of berries and anthocyanin-containing foods on the metabolic syndrome are not always supported by findings of interventional studies in humans, and thus further studies are necessary. Use of standardized diets and conditions by all research groups may address this problem. Berries are tasty foods that are easy to consume, and thus, investigating their health benefits is critical for health promotion and disease prevention. PMID:27058561

  8. Evaluation of Anti-Inflammatory, Anti-diabetic activityof Indian Bauhinia vahlii (stembark)

    Institute of Scientific and Technical Information of China (English)

    Das Surya Narayan; Patro Varanashi Jagannath; Dinda Subas Chandra

    2012-01-01

    Objective: To evaluate the anti-inflammatory and antidiabetic property of Bauhinia vahlii (stem bark) with preliminary phytochemical profile of the extracts. Methods: The dried whole plant material (1400 g) was packed in soxhlet apparatus and extracted successively with Pet. Ether (PE) to defat the drug, petroleum ether was removed from the powdered defatted drug which was then extracted with benzene (BE), chloroform(CE) and 95% of Ethanol (EE) as increasing polarity and all extracts screened for anti-inflammatory and antidiabetic activity using carrageenan induced paw edema and streptozotacin induced diabetic respectively. The toxicity and phytochemical screening were done using standard procedure. Result: The preliminary phytochemical tests revealed the presence of alkaloids, flavonoids, phytosterol, phenolic compounds, and glycoside. While carbohydrates, protein, gums and amino acids were absent. The acute toxicity study of various extracts of Bauhinia vahlii was conducted and dose of 353 mg/kg is fixed for anti-inflammatory and antidiabetic perperty. The pet ether, chloroform and ethanolic extract ofBauhinia vahlii significantly decreased the paw edema induced by carrageenin in rats at a dose of 353 mg/kg comparable to standard ibuprofen (100 mg/kg). Similarly in case of antidiabetic property, the ethanolic and chloroform extract of Bauhinia vahlii at a dose level 353 mg/kg, showed significant reduction in blood sugar level from 2 to 24 h in progressive manner comparable to standard glibenclamide (5mg/kg).

  9. Existence of Anti-periodic Solution for Differential Equations

    Institute of Scientific and Technical Information of China (English)

    FU NING

    2010-01-01

    In this paper,we discuss the anti-periodic boundary value problem for a class of first order differential equations.By using homotopy method,we obtain the conditions for the existence of anti-periodic solution for the equation under consideration.This result can be extended to higher order differential equations.

  10. A Synthesis Method for Static Anti-Windup Compensators

    OpenAIRE

    Solyom, Stefan

    2003-01-01

    Synthesis of static anti-windup compensators is considered. LMIconditions are established for stability and performance analysis of the closedloop system. The performance criterion describes the servo problem forthe resulting closed-loop piecewise linear system. The synthesisof the anti-windup compensators will be given by some bilinear matrix inequalities.

  11. Antidepressant and anti-stress effects of curcumin inmice

    Institute of Scientific and Technical Information of China (English)

    YingXU; Bao-shanKU; Hai-yanYAO; Yong-heZHANG; Xue-junLI

    2004-01-01

    Curcumin (diferuloylmethane), a yellow colouring agent contained in the rhizome of Curcuma Longa (turmeric), has a wide array of pharmacological and biological activities, such as antioxidant, anti-inflammatory, immunomodulating and anticarcinogenic effects. In this study, curcumin was examined for the antidepressant and anti-stress effects in forced swimming,

  12. Shoes and Toys: Victims of Anti-Dumpling

    Institute of Scientific and Technical Information of China (English)

    Guo Liqin

    2009-01-01

    @@ The anti-dumping duties imposed on China have long been a subject of intense dispute. According to statistics released by the WTO, China is the country most frequently targeted by other countries for anti-dumping investigation against its exports.

  13. The Implications of Christian Anti-Semitism for Educators.

    Science.gov (United States)

    O'Reilly, Patricia

    1995-01-01

    Maintains that the history of anti-Semitism has historical links to Christian theology. Asserts that Christianity provided ample fuel for the secular anti-Semitism preached by Hitler and the Nazi party. Contends that educators can draw important lessons on the value of education and the pedagogy of teaching history. (CFR)

  14. Proofpoint unveils the industry's most advanced anti-spam laboratory

    CERN Multimedia

    2003-01-01

    "Proofpoint, Inc., the leader in large enterprise anti-spam solutions, today unveiled its Anti-Spam Laboratory, the world's most advanced center for spam research and analysis, and the first to be based on advanced Machine Learning science" (1 page).

  15. Anti-synchronization Between Lorenz and Liu Hyperchaotic Systems

    Institute of Scientific and Technical Information of China (English)

    ZHENG Qiang; ZHANG Xiao-Ping; REN Zhong-Zhou

    2008-01-01

    Anti-synchronization between different hyperchaotic systems is presented using Lorenz and Liu systems.When the parameters of two systems are known,one can use active synchronization.When the parameters are unknown or uncertain,the adaptive synchronization is applied.The simulation results verify the effectiveness of the proposed two schemes for anti-synchronization between different hyperehaotic systems.

  16. Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M;

    2001-01-01

    To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

  17. Anti-Enterovirus 71 Agents of Natural Products.

    Science.gov (United States)

    Wang, Liyan; Wang, Junfeng; Wang, Lishu; Ma, Shurong; Liu, Yonghong

    2015-01-01

    This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded. PMID:26370955

  18. Monitoring and treatment of anti-D in pregnancy

    DEFF Research Database (Denmark)

    Bettelheim, D; Panzer, S; Reesink, H W;

    2010-01-01

    Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the in...

  19. Anti-Money Laundering Efforts - Failures, Fixes and the Future

    NARCIS (Netherlands)

    Deleanu, I.S.

    2015-01-01

    In this PhD thesis I address important topics in the debate on and the organisation of the Anti-Money Laundering efforts, which are related to the legitimacy and the effectiveness of the Anti-Money Laundering policies. First of all, this thesis provides a reflection on the assessments of concern tha

  20. Study of anti-inflammatory effect of simvastatin in rats

    Directory of Open Access Journals (Sweden)

    Ranga Satya Venkatesh

    2016-08-01

    Results: At a dose of 40 mg Simvastatin showed anti-inflammatory effect which is statically highly significant. Conclusions: However, the above preclinical experiments only give us an idea about the anti-inflammatory activity, but large scale clinical trials are necessary for final assessment. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1520-1523