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Sample records for anti cd-20 c2b8

  1. CD20-induced B cell death can bypass mitochondria and caspase activation

    NARCIS (Netherlands)

    van der Kolk, L. E.; Evers, L. M.; Omene, C.; Lens, S. M. A.; Lederman, S.; van Lier, R. A. W.; van Oers, M. H. J.; Eldering, E.

    2002-01-01

    The apoptotic pathway activated by chimeric anti-CD20 monoclonal antibodies (rituximab, IDEC.C2B8) was analyzed using the Burkitt lymphoma cell line Ramos. Crosslinking of CD20 (CD20XL) induced apoptosis in Ramos cells, which involved loss of mitochondrial membrane potential (Deltapsi(m)), the

  2. 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)

    Torres G, E.

    2007-01-01

    The purpose of this investigation was to prepare 131 I-anti-CD20 and 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 131 I-anti-CD20 and 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. 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 188 Re-anti-CD20, 125 I-anti-CD20 (positive control) and 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. 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 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 188 Re-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

  3. 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

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

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    Kuramoto, Graciela Barrio

    2016-10-01

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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Joel Reis

    2016-01-01

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

  7. Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration.

    Science.gov (United States)

    Hunt, Christine M; Beste, Lauren A; Lowy, Elliott; Suzuki, Ayako; Moylan, Cynthia A; Tillmann, Hans L; Ioannou, George N; Lim, Joseph K; Kelley, Michael J; Provenzale, Dawn

    2016-05-21

    To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ(2) test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Development of a lyophilized formulation for preparing the radiopharmaceutical 177Lu-DOTA-Anti-CD20

    International Nuclear Information System (INIS)

    Serrano E, L. A.

    2015-01-01

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

  10. Compartmental and dosimetric studies of anti-CD20 labelled with 188Re

    International Nuclear Information System (INIS)

    Kuramoto, Graciela Barrio

    2016-01-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β - emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β - emitters as 131 I, 90 Y, 188 Re 177 Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). 188 Re (E β = 2.12 MeV; E γ = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, 188 Re can be obtained from a radionuclide generator of 188 W/ 188 Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical 188 Re-Anti-CD20, where the radionuclide can be obtained from a generator system 188 W/ 188 Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with 188 Re with the marking of the antibody with 90 Y, 131 I, 177 Lu and 99m Tc (for their similar chemical characteristics) and 211 At, 213 Bi, 223 Ra and 225 Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for 188 Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of 188 Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β -131 I-labeled anti CD20, 177 Luanti- CD20, the γ emitter 99m Tc-Anti-CD20 and α emitter 211 At-Anti-CD20 presented a elimination constant of approximately 0.05 hours

  11. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma

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    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China); Hsu, Yu-Shen, E-mail: yshsu@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Chang, Mingi, E-mail: mingi.chang@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Hsu, Chuan-Lung, E-mail: fabio@dcb.org.tw [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China)

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

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

    International Nuclear Information System (INIS)

    Pantoja H, I.E.

    2004-01-01

    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 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

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

    Directory of Open Access Journals (Sweden)

    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

  14. Subcutaneous veltuzumab, a humanized anti-CD20 antibody, in the treatment of refractory pemphigus vulgaris.

    Science.gov (United States)

    Ellebrecht, Christoph T; Choi, Eun J; Allman, David M; Tsai, Donald E; Wegener, William A; Goldenberg, David M; Payne, Aimee S

    2014-12-01

    IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse, and intravenous rituximab infusions are expensive. Therefore, cost-effective anti-CD20 therapies are desirable.OBSERVATIONS A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second-generation humanized anti-CD20 antibody, to a patient with refractory PV. Veltuzumab was administered as two 320-mg (188mg/m2) subcutaneous doses 2 weeks apart, resulting in complete remission of disease off therapy. The disease relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab, using the same dosage regimen, again induced complete remission off therapy, which remained at9 months. No serious adverse events occurred during 35 months of follow-up. Serum veltuzumab levels were 22 and 29 μg/mL 2 weeks after the first dose of each cycle, and the drug remained detectable in the serum for longer than 3 months. Relapse and response to veltuzumab generally correlated with desmoglein 3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that occurred after a long-term remission, the patient demonstrated an elevated naive (CD19+CD27−) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional (CD19+CD24+CD38+) B-cell frequency of 12.5%.CONCLUSIONS AND RELEVANCE Subcutaneous veltuzumab may be a safe, effective, and more economical alternative to intravenous rituximab for PV therapy. Clinical trials of subcutaneous veltuzumab for PV are warranted.

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

    International Nuclear Information System (INIS)

    Perera Pintado, Alejandro; Leyva Montaña, René; Prats Capote, Anaís; Góngora Bravo, Magdiel; Alberti Ramírez, Alejandro; León, Mariela; Hernández González, Ignacio; Dorvignit, Denise

    2016-01-01

    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 90 Sr- 90 Y 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

  16. 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.

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

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

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined. Copyright © 2014 by the American Academy of Pediatrics.

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

    International Nuclear Information System (INIS)

    Dias, Carla Roberta de Barros Rodrigues

    2010-01-01

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

  19. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD)

    NARCIS (Netherlands)

    Oertel, SHK; Verschuuren, E; Reinke, P; Zeidler, K; Papp-Vary, M; Babel, N; Trappe, RU; Jonas, S; Hummel, M; Anagnostopoulos, [No Value; Dorken, B; Riess, HB

    2005-01-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April

  20. Radiolabeling and Preclinical Evaluation of 131I-anti-CD20 for Non-Hodgkin's Lymphomas Therapy

    International Nuclear Information System (INIS)

    Kullaprawittaya, Usa; Khongpetch, Pranom; Ngamprayad, Tippanan; Nuanchuen, Suphatphong

    2007-08-01

    Full text: In this study, a monoclonal anti-CD20 was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma by reacting anti-CD20 with iodine-131 using iodogen procedure. It was found that radiochemical yield was > 95 % independently of incubation time and the antibody could be conjugated with iodine-131 up to 10 mCi/mg. The radiolabeled antibody exhibited excellent retention of immunoreactivity with radio incorporations >95% for 6 hr at 4 o C. In vitro stability tests showed minimal loss of iodine-131 from the conjugate in the presence of cysteine and in human serum at 37 o C. Biodistribution study in normal ICR mice showed higher uptake by the liver, kidney and intestines but lower thyroid uptake compared to 131 I -MIBG. Biodistribution studies confirmed the in vitro stability of 131 I -anti-CD20. In particular, excellent in vivo retention of iodine-131 was demonstrated by lower thyroid accumulation over 48 hr. A favorable biological distribution of 131 I -anti-CD20 suggests this radiopharmaceutical may be effectively used in the therapy of non-Hodgkin's lymphoma

  1. Optimization of 90 Y-antiCD20 preparation for radioimmunotherapy

    Directory of Open Access Journals (Sweden)

    Nazila Gholipour

    2013-01-01

    Full Text Available Context: The advent of monoclonal antibodies such as Rituximab, in recent years, has brought about decisive progress in the treatment of aggressive and indolent non-Hodgkin′s lymphoma. Aims: A further tried and tested improvement to the unmodified antibody has been its coupling to the beta-emitters Y-90. The optimization of 90 Y-antiCD20 radioimmunoconjugate production and quality control methods for future clinical studies in the country was targeted in this work. Materials and Methods: The antibody was labeled with 90 Y-yttrium chloride (185 MBq after conjugation with freshly prepared ccDTPA. Y-90 chloride was obtained by thermal neutron flux (4 × 10 13 n/cm 2 /s of a natural Y 2 O 3 sample, dissolved in acidic media. Radiolabeling was completed in 24 h by the addition of DTPA-Rituximab conjugate at room temperature. Statistical Analysis Used: All values were expressed as mean ± standard deviation (mean ± SD, and the data were compared using Student′s t-test. Statistical significance was defined as P < 0.05. Results: Radiochemical purity of 96% was obtained by using ITLC method for the final radioimmunoconjugate (specific activity = 440-480 MBq/mg. The final isotonic 90 Y-Rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 72 h. Conclusion: The results showed that 90 Y-DTPA-Rituximab could be considered for further evaluation in animals and possibly in humans as a radiopharmaceutical for use in radioimmunotherapy against non-Hodgkin′s lymphomas. Because of the importance of developing anti-lymphoma B agents in nuclear medicine for country use, an optimized radiolabeling method has been introduced.

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

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

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

  3. 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

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

    International Nuclear Information System (INIS)

    Hassan Yousefnia; Amir Reza Jalilian; Ali Bahrami-Samani; Simindokht Shirvani-Arani; Mohammad Ghannadi-Maragheh; Azim Arbabi; Edalat Radfar

    2011-01-01

    Rituximab was successively labeled with 177 Lu-lutetium chloride. 177 Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm -2 s -1 ) of natural Lu 2 O 3 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 CH 2 Cl 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 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 177 Lu-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)

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

    International Nuclear Information System (INIS)

    Dias, C.R.; Osso Junior, J.A.

    2008-01-01

    Radioimmunotherapy (RIT) uses target-specific monoclonal antibodies or fragments labeled with a radioactive isotope to combine humoral and radiolytic functions and has the advantage of targeting not only the cell to which the antibody is bound but also the surrounding tumor cells and microenvironment. The most successful clinical studies of RIT in patients with Non-Hodgkin's Lymphoma (NHL) have targeted CD20+ Bcell tumors. 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 ( 188 Re) is currently produced from the father nuclide 188 W through a transportable generator system. Because of its easy availability and suitable nuclear properties (E βMAX = 2.1 MeV, t1/2 = 16.9 h, E γ = 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 objective of this work is the optimization of direct radiolabeling method of anti-CD20 with 188 Re using a liquid formulation. Anti-CD20 was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulphydryl groups was assayed with Ellman's reagent. Optimization of radiolabeling was achieved by varying parameters: antibody mass, reducing agent mass, tartrate mass, stability and reaction time, 188 Re volume and activity. Radiochemical purity of 188 Re-anti-CD20 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 but further studies will be carried out in order to improve the labeling yields and consequently the specific activity of the product. (author)

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

    International Nuclear Information System (INIS)

    Miranda O, R. M.

    2014-01-01

    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

  7. 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

  8. Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Jungersen, Mette B; Pedersen, Charlotte D

    2011-01-01

    complex from the B-cell surface. Here, we confirm, that in vitro co-culture of human monocytes and RTX-labelled syngeneic B cells results in reduced expression of CD20/RTX complex on the B cell surface. This shaving mechanism was the result of active protease activity because EDTA and PMSF were able...

  9. Evaluation of cell cycle changes activated by the administration of {sup 177}Lu-DOTA-antiCD20; Evaluacion de cambios en el ciclo celular activados por la administracion de {sup 177}Lu-DOTA-antiCD20

    Energy Technology Data Exchange (ETDEWEB)

    Ramos B, J. C.

    2016-07-01

    In the present project, cytometric evaluation of cell cycle changes induced by the {sup 177}Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

  10. Evaluation of cell cycle changes activated by the administration of 177Lu-DOTA-antiCD20

    International Nuclear Information System (INIS)

    Ramos B, J. C.

    2016-01-01

    In the present project, cytometric evaluation of cell cycle changes induced by the 177 Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

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

    Science.gov (United States)

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

    2016-10-04

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

  12. Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human beta-glucuronidase for antibody-directed enzyme prodrug therapy

    NARCIS (Netherlands)

    Haisma, HJ; Sernee, MF; Hooijberg, E; Brakenhoff, RH; van den Meulen-Mulleman, IH; Pinedo, HM; Boven, E

    1998-01-01

    The CD20 antigen is an attractive target for specific treatment of B-cell lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a tumor-specific antibody such as anti-CD20. We constructed a fusion

  13. 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

  14. In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    International Nuclear Information System (INIS)

    Forrer, Flavio; Mueller-Brand, Jan; Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R.; Lohri, Andreas; Moldenhauer, Gerhard

    2009-01-01

    131 I- and 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 ( 177 Lu or 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 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 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 177 Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 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.)

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

    International Nuclear Information System (INIS)

    Barrio, Graciela; Osso Junior, Joao A.

    2011-01-01

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

  16. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies.

    Science.gov (United States)

    Tipton, Thomas R W; Roghanian, Ali; Oldham, Robert J; Carter, Matthew J; Cox, Kerry L; Mockridge, C Ian; French, Ruth R; Dahal, Lekh N; Duriez, Patrick J; Hargreaves, Philip G; Cragg, Mark S; Beers, Stephen A

    2015-03-19

    Following the success of rituximab, 2 other anti-CD20 monoclonal antibodies (mAbs), ofatumumab and obinutuzumab, have entered clinical use. Ofatumumab has enhanced capacity for complement-dependent cytotoxicity, whereas obinutuzumab, a type II mAb, lacks the ability to redistribute into lipid rafts and is glycoengineered for augmented antibody-dependent cellular cytotoxicity (ADCC). We previously showed that type I mAbs such as rituximab have a propensity to undergo enhanced antigenic modulation compared with type II. Here we assessed the key effector mechanisms affected, comparing type I and II antibodies of various isotypes in ADCC and antibody-dependent cellular-phagocytosis (ADCP) assays. Rituximab and ofatumumab depleted both normal and leukemic human CD20-expressing B cells in the mouse less effectively than glycoengineered and wild-type forms of obinutuzumab, particularly when human immunoglobulin G1 (hIgG1) mAbs were compared. In contrast to mouse IgG2a, hIgG1 mAbs were ineffective in ADCC assays with murine natural killer cells as effectors, whereas ADCP was equivalent for mouse IgG2a and hIgG1. However, rituximab's ability to elicit both ADCC and ADCP was reduced by antigenic modulation, whereas type II antibodies remained unaffected. These data demonstrate that ADCP and ADCC are impaired by antigenic modulation and that ADCP is the main effector function employed in vivo. © 2015 by The American Society of Hematology.

  17. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Floyd Hassenrück

    2018-01-01

    Full Text Available The antibody-dependent cell-mediated cytotoxicity (ADCC of the anti-CD20 monoclonal antibodies (mAbs rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability. The cytotoxicity owing to alloreactivity was less susceptible to interference by KI than the ADCC of anti-CD20 mAbs, which was markedly diminished by ibrutinib, but not by idelalisib. Compared to rituximab, the ADCC of obinutuzumab against primary CLL cells showed approximately 30% higher efficacy and less interference with KI. Irreversible BTK inhibitors at a clinically relevant concentration of 1 μM only weakly impaired the ADCC of anti-CD20 mAbs, with less influence in combinations with obinutuzumab than with rituximab and by acalabrutinib than by ibrutinib or tirabrutinib. In summary, NK cell line-based assays permitted the sensitive detection of ADCC of therapeutic anti-CD20 mAbs against CLL cells and of the interference of KI with this important killing mechanism.

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

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

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

  19. Evaluation of the cell death mechanisms activated by the radiopharmaceutical 177Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy

    International Nuclear Information System (INIS)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G.

    2016-10-01

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

  20. Romidepsin alone or in combination with anti-CD20 chimeric antigen receptor expanded natural killer cells targeting Burkitt lymphomain vitroand in immunodeficient mice.

    Science.gov (United States)

    Chu, Yaya; Yahr, Ashlin; Huang, Brian; Ayello, Janet; Barth, Matthew; S Cairo, Mitchell

    2017-01-01

    Facilitating the development of alternative targeted therapeutic strategies is urgently required to improve outcome or circumvent chemotherapy resistance in children, adolescents, and adults with recurrent/refractory de novo mature B-cell (CD20) non-Hodgkin lymphoma, including Burkitt lymphoma (BL). Romidepsin, a histone deacetylase inhibitor (HDACi), has been used to treat cutaneous T-cell lymphoma. We have demonstrated the significant anti-tumor effect of anti-CD20 chimeric antigen receptor (CAR) modified expanded peripheral blood natural killer (exPBNK) against rituximab-sensitive and -resistant BL. This study examined the anti-tumor activity of romidepsin alone and in combination with anti-CD20 CAR exPBNKs against rituximab-sensitive and -resistant BL in vitro and in vivo . We found that romidepsin significantly inhibited both rituximab-sensitive and -resistant BL cell proliferation in vitro (P cell death in rituximab-sensitive Raji (P cell cycle arrest in rituximab-resistant Raji-2R and Raji-4RH (P NSG mice. We also demonstrated that romidpesin significantly induced the expression of Natural Killer Group 2, Member D (NKG2D) ligands MICA/B in both rituximab-sensitive and -resistant BL cells (P cell death in BL cells in vitro , reduced tumor burden and enhanced survival in humanized BL xenografted NSG mice (p < 0.05). Our data suggests that romidepsin is an active HDAC inhibitor that also potentiates expanded NK and anti-CD20 CAR exPBNK activity against rituximab-sensitive and -resistant BL.

  1. Estudo comparativo da marcação do anticorpo anti-CD20 com 188Re

    OpenAIRE

    Carla Roberta de Barros Rodrigues Dias

    2010-01-01

    A Medicina Nuclear é uma modalidade de particular importância em oncologia e a investigação de novos radiofármacos direcionados a tumores, seja para diagnóstico e/ou terapia, é uma área de interesse para os pesquisadores. Rituximab (RTX) é um anticorpo monoclonal (AcM) quimérico (IgG 1) que se liga especificamente ao antígeno CD20 com alta afinidade e tem sido usado com sucesso para tratar Linfoma Não-Hodgkin (LNH) de células-B. O antígeno CD20 é expresso sobre mais de 90% dos LNH de células-...

  2. 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.

  3. Unusual Closure of the Ten-Vertex Nido Cage via Alkylation: Regiospecific Synthesis of 3-Alkyl Derivatives of closo-1,2-C2B8H10

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Tok, Oleg L.; Holub, Josef

    2018-01-01

    Roč. 57, č. 3 (2018), s. 1368-1372 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : electrophilic halogenation * nido-5,6-c2b8h12 * carboranes * decaborane * boranes * 5,6-dicarba-nido-decaborane(12) Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 4.857, year: 2016

  4. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin's lymphoma.

    Science.gov (United States)

    Negrea, George O; Elstrom, Rebecca; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Farber, Charles M; Teoh, Nick; Horne, Heather; Wegener, William A; Goldenberg, David M

    2011-04-01

    Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).

  5. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

    Science.gov (United States)

    Negrea, George O.; Elstrom, Rebecca; Allen, Steven L.; Rai, Kanti R.; Abbasi, Rashid M.; Farber, Charles M.; Teoh, Nick; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2011-01-01

    Background Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. Design and Methods A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2nd generation anti-CD20 antibody veltuzumab in patients with CD20+ indolent non-Hodgkin’s lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Conclusions Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin’s lymphoma. (Clinicaltrials.gov identifier: NCT00546793) PMID:21173095

  6. 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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Martinez V, B. E.

    2016-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-15

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

  9. Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma.

    Science.gov (United States)

    Thakral, Parul; Singla, Suhas; Vashist, Atul; Yadav, Madhav P; Gupta, Santosh K; Tyagi, Jaya S; Sharma, Atul; Bal, Chandra S; Snehlata, EmptyYN Y; Malhotra, Arun

    2016-01-01

    The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL). Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy. No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively. 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.

  10. Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.

    Science.gov (United States)

    Parrino, Janie; McNeil, Shelly A; Lawrence, Steven J; Kimby, Eva; Pagnoni, Marco F; Stek, Jon E; Zhao, Yanli; Chan, Ivan S F; Kaplan, Susan S

    2017-03-27

    Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZV IN ) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZV IN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZV IN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZV IN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ZV IN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-valuevaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZV IN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. In adults with HM receiving anti-CD20 monoclonal antibodies, ZV IN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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)

    Akanji, Akinkunmi Ganiyu

    2006-01-01

    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

  12. 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)

    Akanji, Akinkunmi Ganiyu

    2006-01-01

    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 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

  13. Efficacy and safety of anti-CD20 antibody rituximab for patients with refractory systemic lupus erythematosus.

    Science.gov (United States)

    Iwata, S; Saito, K; Hirata, S; Ohkubo, N; Nakayamada, S; Nakano, K; Hanami, K; Kubo, S; Miyagawa, I; Yoshikawa, M; Miyazaki, Y; Yoshinari, H; Tanaka, Y

    2018-04-01

    Objective We examined the efficacy and safety of rituximab in patients with refractory systemic lupus erythematosus (SLE). Methods The study enrolled 63 SLE patients who were treated with rituximab between 2002 and 2015. The participants underwent a battery of tests before treatment and at one year. Treatment ranged from two to four times at 500 or 1000 mg. Results Baseline characteristics were males:females = 6:57, age 33.9 years, and disease duration 87.2 months. The primary endpoint: The rate of major clinical response (MCR) was 60% while the partial clinical response (PCR) was 25%. Thirty of 36 (83%) patients with lupus nephritis (WHO II: 2, III: 5, IV: 22, V: 4, IV+V: 2, not assessed: 1) and 22 of 24 patients (92%) with neuropsychiatric SLE, who could be followed at one year, showed changes from BILAG A or B score to C or D score at one year. Multivariate analysis identified high anti-dsDNA antibody and shorter disease duration as significant determinants of MCR at one year. Repeat examination was conducted at five years. Primary failure was recorded in 8.8% and secondary failure in 32.4% (time to relapse: 24.4 months). Rituximab was well tolerated although 65 adverse events, mostly infections, were recorded within one year. Conclusion Rituximab is potentially efficacious for the treatment of patients with refractory SLE.

  14. 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)

    Liu, S Y.; Eary, Janet F.; Petersdorf, S H.; Martin, P J.; Maloney, D G.; Applebaum, F. R.; Matthews, D. C.; Bush, S A.; Durack, L. D.; Fisher, Darrell R.; Gooley, T A.; Bernstein, I. D.; Press, O. W.

    1997-01-01

    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

  15. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  16. Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves' orbitopathy: A five-year follow-up study.

    Science.gov (United States)

    Erdei, Annamaria; Paragh, Gyorgy; Kovacs, Peter; Karanyi, Zsolt; Berenyi, Ervin; Galuska, Laszlo; Lenkey, Agota; Szabados, Lajos; Gyory, Ferenc; Ujhelyi, Bernadett; Berta, Andras; Boda, Judit; Berta, Eszter; Bodor, Miklos; Gazdag, Annamaria; Nagy, Endre V

    2014-12-01

    Abstract The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves' orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), (99m)Tc-labeled diethylene triamine pentaacetic acid ((99m)Tc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375 mg/m(2) body surface area for four weeks. The mean follow-up period was 67 (range 58-81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5 ± 1.7 and decreased to 3.4 ± 1.6 by one month (p < 0.05) and remained unchanged (3.2 ± 1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52 ± 4.51 MBq/cm(3) and decreased to 11.97 ± 2.36 MBq/cm(3) at one year (p < 0.002). The mean of T2 relaxation times before and one year after therapy were 96.91 ± 17.61 ms and 84.29 ± 9.41 ms, respectively (p < 0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4 ± 3.4 U/L, 5.6 ± 4.5 U/L and 1.7 ± 1.5 U/L, respectively (p < 0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.

  17. 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

    NARCIS (Netherlands)

    Coiffier, Bertrand; Lepretre, Stéphane; Pedersen, Lars Møller; Gadeberg, Ole; Fredriksen, Henrik; van Oers, Marinus H. J.; Wooldridge, James; Kloczko, Janusz; Holowiecki, Jerzy; Hellmann, Andrzej; Walewski, Jan; Flensburg, Mimi; Petersen, Jørgen; Robak, Tadeusz

    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, infusions

  18. 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

  19. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical 177Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy

    International Nuclear Information System (INIS)

    Martinez V, B. E.

    2016-01-01

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

  20. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

  1. Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen.

    Science.gov (United States)

    Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

    2017-03-01

    Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  2. 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, infusions...... rate of cohort C was 50% (13/26), one patient having a nodular partial remission and 12 patients partial remission. In conclusion, ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia (CLL) in doses up to 2000 mg. Preliminary data on safety and objective response...

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

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William

    2010-01-01

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

  4. Effectiveness and side effects of anti-CD20 therapy for autoantibody-mediated blistering skin diseases: A comprehensive survey of 71 consecutive patients from the Initial use to 2007

    Directory of Open Access Journals (Sweden)

    Jennifer D Peterson

    2008-11-01

    Full Text Available Jennifer D Peterson1, Lawrence S Chan2,3,41Department of Dermatology, Texas Tech University Health Sciences Center at Lubbock, Lubbock, TX, USA; 2Department of Dermatology; 3Department of Microbiology/Immunology, University of Illinois at Chicago, Chicago, IL, USA; 4Medicine Service, Jesse Brown VA Medical Center, Chicago, IL, USAAbstract: In order to examine the efficacy and side effects of the monoclonal antibody anti-CD20 (rituximab on autoimmune blistering skin diseases, we performed a comprehensive survey of 71 consecutive patients from initial use up to 2007, using the PubMed database. A heterogeneous group of patients, including 51 patients with pemphigus vulgaris, one with pemphigus vegetans, nine with pemphigus foliaceus, five with paraneoplastic pemphigus, four with epidermolysis bullosa acquisita, and one with both bullous pemphigoid and graft vs host disease was included in this survey. Overall the monoclonal antibody seems to be effective in that 69% of patients showed complete response, 25% of patients showed partial response, whereas 6% of patients showed progressive disease. Six deaths occurred in association with the treatment, with four of these deaths in patients with paraneoplastic pemphigus, a disease characteristically resistant to conventional medication and with a high mortality rate. Of note, 11 patients who received combined rituximab and intravenous immune globulin treatments had the best outcome: complete response without any serious side effects. Therefore further investigation on rituximab with controlled clinical trial is a worthy pursuit.Keywords: blistering diseases, skin, anti-CD20, pemphigus, epidermolysis bullosa acquisita

  5. Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome

    Science.gov (United States)

    Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

    2016-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B

  6. 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.

  7. Loss of Intra-Islet CD20 Expression May Complicate Efficacy of B-Cell–Directed Type 1 Diabetes Therapies

    Science.gov (United States)

    Serreze, David V.; Chapman, Harold D.; Niens, Marijke; Dunn, Robert; Kehry, Marilyn R.; Driver, John P.; Haller, Michael; Wasserfall, Clive; Atkinson, Mark A.

    2011-01-01

    OBJECTIVE Consistent with studies in NOD mice, early clinical trials addressing whether depletion of B cells by the Rituximab CD20-specific antibody provides an effective means for type 1 diabetes reversal have produced promising results. However, to improve therapeutic efficacy, additional B-cell–depleting agents, as well as attempts seeking diabetes prevention, are being considered. RESEARCH DESIGN AND METHODS Autoantibodies, including those against insulin (IAAs), are used to identify at-risk subjects for inclusion in diabetes prevention trials. Therefore, we tested the ability of anti-CD20 to prevent diabetes in NOD mice when administered either before or after IAA onset. RESULTS The murine CD20-specific 18B12 antibody that like Rituximab, depletes the follicular (FO) but not marginal zone subset of B cells, efficiently inhibited diabetes development in NOD mice in a likely regulatory T-cell–dependent manner only when treatment was initiated before IAA detection. One implication of these results is that the FO subset of B cells preferentially contributes to early diabetes initiation events. However, most important, the inefficient ability of anti-CD20 treatment to exert late-stage diabetes prevention was found to be attributable to downregulation of CD20 expression upon B cell entry into pancreatic islets. CONCLUSIONS These findings provide important guidance for designing strategies targeting B cells as a potential means of diabetes intervention. PMID:21926271

  8. Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

    NARCIS (Netherlands)

    de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

    2018-01-01

    Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

  9. Automated Manufacturing of Potent CD20-Directed Chimeric Antigen Receptor T Cells for Clinical Use.

    Science.gov (United States)

    Lock, Dominik; Mockel-Tenbrinck, Nadine; Drechsel, Katharina; Barth, Carola; Mauer, Daniela; Schaser, Thomas; Kolbe, Carolin; Al Rawashdeh, Wael; Brauner, Janina; Hardt, Olaf; Pflug, Natali; Holtick, Udo; Borchmann, Peter; Assenmacher, Mario; Kaiser, Andrew

    2017-10-01

    The clinical success of gene-engineered T cells expressing a chimeric antigen receptor (CAR), as manifested in several clinical trials for the treatment of B cell malignancies, warrants the development of a simple and robust manufacturing procedure capable of reducing to a minimum the challenges associated with its complexity. Conventional protocols comprise many open handling steps, are labor intensive, and are difficult to upscale for large numbers of patients. Furthermore, extensive training of personnel is required to avoid operator variations. An automated current Good Manufacturing Practice-compliant process has therefore been developed for the generation of gene-engineered T cells. Upon installation of the closed, single-use tubing set on the CliniMACS Prodigy™, sterile welding of the starting cell product, and sterile connection of the required reagents, T cells are magnetically enriched, stimulated, transduced using lentiviral vectors, expanded, and formulated. Starting from healthy donor (HD) or lymphoma or melanoma patient material (PM), the robustness and reproducibility of the manufacturing of anti-CD20 specific CAR T cells were verified. Independent of the starting material, operator, or device, the process consistently yielded a therapeutic dose of highly viable CAR T cells. Interestingly, the formulated product obtained with PM was comparable to that of HD with respect to cell composition, phenotype, and function, even though the starting material differed significantly. Potent antitumor reactivity of the produced anti-CD20 CAR T cells was shown in vitro as well as in vivo. In summary, the automated T cell transduction process meets the requirements for clinical manufacturing that the authors intend to use in two separate clinical trials for the treatment of melanoma and B cell lymphoma.

  10. Activatory and Inhibitory Fcγ Receptors Augment Rituximab-mediated Internalization of CD20 Independent of Signaling via the Cytoplasmic Domain*

    Science.gov (United States)

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

    2015-01-01

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. PMID:25568316

  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. [Refractory CD20-positive peripheral T-cell lymphoma showing loss of CD20 expression after rituximab therapy and gain of CD20 expression after administration of vorinostat and gemcitabine].

    Science.gov (United States)

    Teshima, Kazuaki; Ohyagi, Hideaki; Kume, Masaaki; Takahashi, Satsuki; Saito, Masahiro; Takahashi, Naoto

    A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse. The patient received the GDP regimen as salvage therapy with the addition of vorinostat for skin involvement; however, he failed to respond, and the disease systemically progressed. Furthermore, he also exhibited progression in the skin after stopping vorinostat due to hematologic toxicity. A lymph node biopsy at progression revealed CD20 re-expression by immunohistochemistry. At progression, the patient received mogamulizumab but failed to respond, and he died owing to disease progression 8 months after relapse. In this case, we demonstrated CD20-negative conversion following rituximab and CD20-positive reversion after using vorinostat and gemcitabine.

  13. Simple Synthesis, Halogenation, and Rearrangement of closo-1,6-C2B8H10

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Padělková, Z.; Růžička, A.

    2015-01-01

    Roč. 34, č. 2 (2015), s. 450-454 ISSN 0276-7333 R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : MAGNETIC-RESONANCE-SPECTROSCOPY * ORGANOELEMENTAL DERIVATIVES * CLOSO-BORANES * CARBORANES * 5,6-DICARBA-NIDO-DECABORANE(12) Subject RIV: CA - Inorganic Chemistry Impact factor: 4.186, year: 2015

  14. Electrophilic Halogenation of closo-1,2-C2B8H10.

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Růžička, A.; Růžičková, Z.; Holub, Josef; Tok, Oleg L.; Štíbr, Bohumil

    2017-01-01

    Roč. 56, č. 10 (2017), s. 5971-5975 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : molecular-structure * ortho-carboranes * spectroscopy Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 4.857, year: 2016

  15. Ten-vertex dicarbaboranes from nido-5,6-C2B8H12

    Czech Academy of Sciences Publication Activity Database

    Štíbr, Bohumil

    2015-01-01

    Roč. 798, DEC (2015), s. 30-35 ISSN 0022-328X R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : Boron * Carboranes * Dicarbaboranes * Mechanisms Subject RIV: CA - Inorganic Chemistry Impact factor: 2.336, year: 2015

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

    Directory of Open Access Journals (Sweden)

    Horvat Mateja

    2011-04-01

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

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

    Science.gov (United States)

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

    2015-02-27

    Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory FcγR, FcγRIIb on the surface of B cells, resulting in immunoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the CD20·mAb·FcγRIIb complex follows, the rate of which correlates with FcγRIIb expression. In contrast, although type II anti-CD20 mAb such as tositumomab and obinutuzumab also interact with and activate FcγRIIb, this interaction fails to augment the rate of CD20·mAb internalization, raising the question of whether ITIM phosphorylation plays any role in this process. We have assessed the molecular requirements for the internalization process and demonstrate that in contrast to internalization of IgG immune complexes, FcγRIIb-augmented internalization of rituximab-ligated CD20 occurs independently of the FcγRIIb ITIM, indicating that signaling downstream of FcγRIIb is not required. In transfected cells, activatory FcγRI, FcγRIIa, and FcγRIIIa augmented internalization of rituximab-ligated CD20 in a similar manner. However, FcγRIIa mediated a slower rate of internalization than cells expressing equivalent levels of the highly homologous FcγRIIb. The difference was maintained in cells expressing FcγRIIa and FcγRIIb lacking cytoplasmic domains and in which the transmembrane domains had been exchanged. This difference may be due to increased degradation of FcγRIIa, which traffics to lysosomes independently of rituximab. We conclude that the cytoplasmic domain of FcγR is not required for promoting internalization of rituximab-ligated CD20. Instead, we propose that FcγR provides a structural role in augmenting endocytosis that differs from that employed during the endocytosis of immune complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells

    NARCIS (Netherlands)

    Engelberts, Patrick J.; Voorhorst, Marleen; Schuurman, Janine; van Meerten, Tom; Bakker, Joost M.; Vink, Tom; Mackus, Wendy J. M.; Breij, Esther C. W.; Derer, Stefanie; Valerius, Thomas; van de Winkel, Jan G. J.; Parren, Paul W. H. I.; Beurskens, Frank J.

    2016-01-01

    Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20(+) B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab ')2 fragments, as well as C1q-binding-deficient IgG mutants,

  19. 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...

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  1. 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

    , 25 patients had been treated with high-dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated...

  2. High CD20+ background cells predict a favorable outcome in classical Hodgkin lymphoma and antagonize CD68+ macrophages.

    Science.gov (United States)

    Panico, Luigi; Tenneriello, Valentina; Ronconi, Fioravante; Lepore, Marianna; Cantore, Nicola; Dell'Angelo, Antonietta Carmela; Ferbo, Ludovica; Ferrara, Felicetto

    2015-06-01

    We studied by immunohistochemistry the background CD20 + cells in 131 cases of classical Hodgkin lymphoma (cHL). High CD20 + dispersed cells (CD20BG) showed a significant correlation with longer overall survival (OS) and a trend toward improved progression-free survival (PFS). At multivariate analysis high CD20BG was also an independent prognostic factor of improved PFS and OS. The prognostic role of CD20BG seems to be opposite with respect to tumor associated macrophages (TAMs) we studied previously in most cases of the series. We scored patients on the basis of the respective CD20BG and TAM count and found that the combination of low CD20BG and high TAMs was related to a significantly reduced PFS and OS at univariate and multivariate analysis. Microenvironment CD20 + cells seem to play a favorable prognostic role in cHL. Depletion of CD20 + cells together with an increase of TAMs identifies a group of patients with high-risk disease.

  3. Click Dehydrogenation of Carbon-Substituted nido-5,6-C2B8H12 Carboranes: A General Route to closo-1,2-C2B8H10 Derivatives

    Czech Academy of Sciences Publication Activity Database

    Tok, Oleg L.; Bakardjiev, Mario; Štíbr, Bohumil; Hnyk, Drahomír; Holub, Josef; Padělková, Z.; Růžička, A.

    2016-01-01

    Roč. 55, č. 17 (2016), s. 8839-8843 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : magnetic-resonance-spectroscopy * structural-characterization * monocarbaborane chemistry Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  4. Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

    DEFF Research Database (Denmark)

    Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

    2016-01-01

    . We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

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

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Tok, Oleg L.; Švec, Petr; Růžičková, Z.; Růžička, A.

    2016-01-01

    Roč. 55, č. 14 (2016), s. 7068-7074 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : boranes * derivatives * magnetic-resonance-spectroscopy Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  6. Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells

    Directory of Open Access Journals (Sweden)

    Xiaomei Wang

    2017-06-01

    Full Text Available Gene-modified B cells expressing immunoglobulin G (IgG fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20. Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV-lentiviral vector (LV and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody formation against hFIX in a mouse model of hemophilia B (HB. In conclusion, transduction of receptor-specific retargeted LV into resting B cells is a promising method to develop B cell therapies for antigen-specific tolerance induction in human disease.

  7. 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)

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

    International Nuclear Information System (INIS)

    Akanji, Akinkunmi Ganiyu

    2012-01-01

    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®). 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)

  9. Selection and Characterization of Single-Stranded DNA Aptamers Binding Human B-Cell Surface Protein CD20 by Cell-SELEX

    Directory of Open Access Journals (Sweden)

    Mansoureh Haghighi

    2018-03-01

    Full Text Available The B-lymphocyte antigen (CD20 is a suitable target for single-stranded (ss nucleic acid oligomer (aptamers. The aim of study was selection and characterization of a ssDNA aptamer against CD20 using Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX. The cDNA clone of CD20 (pcDNA-CD20 was transfected to human embryonic kidney (HEK293T cells. Ten rounds of Cell-SELEX was performed on recombinant HEK-CD20 cells. The final eluted ssDNA pool was amplified and ligated in T/A vector for cloning. The plasmids of positive clones were extracted, sequenced and the secondary structures of the aptamers predicted using DNAMAN® software. The sequencing results revealed 10 different types; three of them had the highest thermodynamic stability, named AP-1, AP-2 and AP-3. The AP-1 aptamer was the most thermodynamically stable one (ΔGAP-1 = −10.87 kcal/mol with the highest binding affinity to CD20 (96.91 ± 4.5 nM. Since, the CD20 is a suitable target for recognition of B-Cell. The selected aptamers could be comparable to antibodies with many advantages. The AP-1, AP-2 and AP-3 could be candidate instead of antibodies for diagnostic and therapeutic applications in immune deficiency, autoimmune diseases, leukemia and lymphoma.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    TM, n¿=¿6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs. RESULTS: PETRIT was obtained with a specific activity of 545....... The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n¿=¿3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n¿=¿6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20...

  11. Anti-lymphoma efficacy comparison of anti-Cd20 monoclonal antibody-targeted and non-targeted star-shaped polymer-prodrug conjugates

    Czech Academy of Sciences Publication Activity Database

    Lidický, Ondřej; Janoušková, Olga; Strohalm, Jiří; Alam, M.; Klener, P.; Etrych, Tomáš

    2015-01-01

    Roč. 20, č. 11 (2015), s. 19849-19864 ISSN 1420-3049 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GA15-02986S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * drug delivery systems * doxorubicin Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.465, year: 2015

  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. Carbon Insertion into arachno-6,9-C2B8H14 via Acyl Chlorides. Skeletal Alkylcarbonation (SAC) Reactions: A New Route for Tricarbollides

    Czech Academy of Sciences Publication Activity Database

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Padělková, Z.; Růžička, A.

    2013-01-01

    Roč. 52, č. 15 (2013), s. 9087-9093 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : MAGNETIC-RESONANCE-SPECTROSCOPY * STRUCTURAL CHARACTERIZATIONS * 12-VERTEX FERRATRICARBOLLIDES Subject RIV: CA - Inorganic Chemistry Impact factor: 4.794, year: 2013

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

    Science.gov (United States)

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

    2013-10-01

    We report the first preclinical in vitro and in vivo comparison of GA101 (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The three antibodies were compared in assays measuring direct cell death (AnnexinV/PI staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and internalization. The models used for the comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was found to be superior to rituximab and ofatumumab in the induction of direct cell death (independent of mechanical manipulation required for cell aggregate disruption formed by antibody treatment), whereas it was 10 to 1,000 times less potent in mediating CDC. GA101 showed superior activity to rituximab and ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable with these two in ADCP. GA101 also showed slower internalization rate upon binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab. When rituximab-pretreated animals were used, second-line treatment with GA101 was still able to control tumor progression, whereas tumors escaped rituximab treatment. Taken together, the preclinical data show that the glyoengineered type II CD20 antibody GA101 is differentiated from the two approved type I CD20 antibodies rituximab and ofatumumab by its overall preclinical activity, further supporting its clinical investigation. ©2013 AACR.

  16. CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

    Science.gov (United States)

    Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

    2017-11-01

    The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  17. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+CD27+CD43+CD70−

    Science.gov (United States)

    Griffin, Daniel O.; Holodick, Nichol E.

    2011-01-01

    B1 cells differ in many ways from conventional B cells, most prominently in the production of natural immunoglobulin, which is vitally important for protection against pathogens. B1 cells have also been implicated in the pathogenesis of autoimmune dyscrasias and malignant diseases. It has been impossible to accurately study B1 cells during health and illness because the nature of human B1 cells has not been successfully defined. This has produced controversy regarding the existence of human B1 cells. Here, we determined the phenotype of human B1 cells by testing sort-purified B cell fractions for three fundamental B1 cell functions based on mouse studies: spontaneous IgM secretion, efficient T cell stimulation, and tonic intracellular signaling. We found that a small population of CD20+CD27+CD43+ cells present in both umbilical cord and adult peripheral blood fulfilled these criteria and expressed a skewed B cell receptor repertoire. These B cells express little or no surface CD69 and CD70, both of which are markedly up-regulated after activation of CD20+CD27−CD43− (naive) and CD20+CD27+CD43− (memory) B cells. This work identifies human B1 cells as CD20+CD27+CD43+CD70−. We determined that the proportion of B1 cells declines with age, which may contribute to disease susceptibility. Identification of human B1 cells provides a foundation for future studies on the nature and role of these cells in human disease. PMID:21220451

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

    Directory of Open Access Journals (Sweden)

    Katy Milne

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

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

    International Nuclear Information System (INIS)

    Kwon, J. H.; Kim, H. G.; Choi, T. H.

    2005-01-01

    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∼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

  20. 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.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  2. Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 zeta Chimeric Antigen Receptor-Modified Effector CD8(+) T Cells

    NARCIS (Netherlands)

    Watanabe, Keisuke; Terakura, Seitaro; Martens, Anton C.; van Meerten, Tom; Uchiyama, Susumu; Imai, Misa; Sakemura, Reona; Goto, Tatsunori; Hanajiri, Ryo; Imahashi, Nobuhiko; Shimada, Kazuyuki; Tomita, Akihiro; Kiyoi, Hitoshi; Nishida, Tetsuya; Naoe, Tomoki; Murata, Makoto

    2015-01-01

    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second-and later-generation CARs simultaneously transmit costimulatory signals with CD3 zeta signals upon ligation, but may lead to severe adverse effects

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

    Directory of Open Access Journals (Sweden)

    Hui Xu

    2010-11-01

    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.

  4. 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)

    Pretscher, Dominik; Distel, Luitpold V; Grabenbauer, Gerhard G; Wittlinger, Michael; Buettner, Maike; Niedobitek, Gerald

    2009-01-01

    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

  5. Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study.

    Science.gov (United States)

    Weide, Rudolf; Pandorf, Annette; Heymanns, Jochen; Köppler, Hubert

    2004-12-01

    We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m2 (80 mg/m2 in CLL) day 1 + 2, (M): 10 mg/m2 day 1 and (R): 375 mg/m2 day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 x BMR followed by 5 x BM. We have treated 54 patients with BMR. Median age was 68 years (36-82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1-7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3-60+). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.

  6. 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

  7. TLR9 ligand (CpG oligodeoxynucleotide induces CLL B-cells to differentiate into CD20+ antibody-secreting cells

    Directory of Open Access Journals (Sweden)

    Hussein eGhamlouch

    2014-06-01

    Full Text Available B-cell chronic lymphocytic leukemia (CLL is the most frequent adult leukemia in the Western world. It is a heterogeneous disease characterized by clonal proliferation and the accumulation of CD5+ mature B lymphocytes. However, the normal counterpart from which the latter cells arise has not yet been identified. CD27 expression and gene expression profiling data suggest that CLL cells are related to memory B-cells. In vitro, memory B-cells differentiate into plasma cells when stimulated with CpG oligodeoxynucleotide (CpG. The objective of the present study was therefore to investigate the ability of CpG, in the context of CD40 ligation, to induce the differentiation of CLL B-cells into antibody-secreting cells (ASCs. CD20+CD38− CLL B-cells were stimulated with a combination of CpG, CD40 ligand and cytokines (CpG/CD40L/c in a two-step, seven-day culture system. We found that the CpG/CD40L/c culture system prompted CLL B-cells to differentiate into CD19+CD20+CD27+CD38- ASCs. These cells secreted large amounts of IgM and had the same shape as plasma cells. However, only IgMs secreted by ASCs that had differentiated from unmutated CLL B-cells were poly/autoreactive. Class-switch recombination to IgG and IgA was detected in cells expressing the activation-induced cytidine deaminase gene (AICDA. Although these ASCs expressed high levels of the transcription factors PRDM1 (BLIMP1, IRF4 and XBP1s, they did not downregulate expression of PAX5. Our results suggest that CLL B-cells can differentiate into ASCs, undergo class-switch recombination and produce poly/autoreactive antibodies. Furthermore, our findings may be relevant for (i identifying the normal counterpart of CLL B-cells and (ii developing novel treatment strategies in CLL.

  8. Prototropic mu-H-8,H-9 and mu-H-9,H-10 Tautomers Derived from the [nido-5,6-C2B8H11](-) Anion

    Czech Academy of Sciences Publication Activity Database

    Tok, Oleg L.; Růžičková, Z.; Růžička, A.; Hnyk, Drahomír; Štíbr, Bohumil

    2016-01-01

    Roč. 55, č. 20 (2016), s. 10122-10124 ISSN 0020-1669 R&D Projects: GA ČR(CZ) GA16-01618S Institutional support: RVO:61388980 Keywords : tautomers Subject RIV: CA - Inorganic Chemistry Impact factor: 4.857, year: 2016

  9. Molecular structures of arachno-decaborane derivatives 6,9-X2B8H10 (X = CH2, NH, Se) including a gas-phase electron-diffraction study of 6,9-C2B8H14

    Czech Academy of Sciences Publication Activity Database

    Hnyk, Drahomír; Bühl, M.; Holub, Josef; Hayes, S. A.; Wann, D. A.; Mackie, I.D.; Borisenko, K.B.; Robertson, H. E.; Rankin, D. W. H.

    2006-01-01

    Roč. 45, č. 15 (2006), s. 6014-6019 ISSN 0020-1669 R&D Projects: GA MŠk LC523 Grant - others:EPSRC(GB) GR/R17768; EPSRC(GB) EP/C513649 Institutional research plan: CEZ:AV0Z40320502 Keywords : nuclear-magnetic-resonance * chemical-shift calculation * density-functional theory Subject RIV: CA - Inorganic Chemistry Impact factor: 3.911, year: 2006

  10. 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...

  11. 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.

    2014-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analogue 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 (PAR) designed to decrease the risk of treatment associated infections and limit 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 analogue 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 9.1 months, and overall survival 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 NK cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that PAR 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

  12. 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. © 2014 Wiley Periodicals, Inc.

  13. Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report.

    Science.gov (United States)

    Ajmi, Houda; Mabrouk, Sameh; Hassayoun, Saida; Regaieg, Haifa; Tfifha, Minyar; Jalel, Chemli; Skouri, Hadef; Zouari, Noura; Abroug, Saoussan

    2017-11-14

    Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.

  14. B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis

    Czech Academy of Sciences Publication Activity Database

    Bruhl, H.; Cihak, J.; Talke, Y.; Rodriguez-Gomez, M.; Hermann, F.; Goebel, N.; Renner, K.; Plachý, Jiří; Stangassinger, M.; Archemann, S.; Nimmerjahn, F.; Mack, M.

    2015-01-01

    Roč. 45, č. 3 (2015), s. 705-715 ISSN 0014-2980 Institutional support: RVO:68378050 Keywords : Arthritis * B cells * B-cell depletion * B-cell inhibition * CD79b * Humoral immune response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.179, year: 2015

  15. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    Science.gov (United States)

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center.

    Science.gov (United States)

    Zhu, Fenlu; Shah, Nirav; Xu, Huiqing; Schneider, Dina; Orentas, Rimas; Dropulic, Boro; Hari, Parameswaran; Keever-Taylor, Carolyn A

    2018-03-01

    Multiple steps are required to produce chimeric antigen receptor (CAR)-T cells, involving subset enrichment or depletion, activation, gene transduction and expansion. Open processing steps that increase risk of contamination and production failure are required. This complex process requires skilled personnel and costly clean-room facilities and infrastructure. Simplified, reproducible CAR-T-cell manufacturing with reduced labor intensity within a closed-system is highly desirable for increased availability for patients. The CliniMACS Prodigy with TCT process software and the TS520 tubing set that allows closed-system processing for cell enrichment, transduction, washing and expansion was used. We used MACS-CD4 and CD8-MicroBeads for enrichment, TransAct CD3/CD28 reagent for activation, lentiviral CD8 TM-41BB-CD3 ζ-cfrag vectors expressing scFv for CD19 or CD20/CD19 antigens for transduction, TexMACS medium-3%-HS-IL2 for culture and phosphate-buffered saline/ethylenediaminetetraacetic acid buffer for washing. Processing time was 13 days. Enrichment (N = 7) resulted in CD4/CD8 purity of 98 ± 4.0%, 55 ± 6% recovery and CD3 + T-cell purity of 89 ± 10%. Vectors at multiplicity of infection 5-10 resulted in transduction averaging 37%. An average 30-fold expansion of 10 8 CD4/CD8-enriched cells resulted in sufficient transduced T cells for clinical use. CAR-T cells were 82-100% CD3 + with a mix of CD4 + and CD8 + cells that primarily expressed an effector-memory or central-memory phenotype. Functional testing demonstrated recognition of B-cells and for the CAR-20/19 T cells, CD19 and CD20 single transfectants were recognized in cytotoxic T lymphocyte and interferon-γ production assays. The CliniMACS Prodigy device, tubing set TS520 and TCT software allow CAR-T cells to be manufactured in a closed system at the treatment site without need for clean-room facilities and related infrastructure. Copyright © 2017 International Society for Cellular Therapy

  17. Przeciwciało monoklonalne przeciw CD20 w terapii postaci rzutowej i pierwotnie postępującej stwardnienia rozsianego – wyniki badań klinicznych III fazy

    Directory of Open Access Journals (Sweden)

    Maciej Maciejowski

    2015-11-01

    Full Text Available Stwardnienie rozsiane to zapalno-demielinizacyjna choroba ośrodkowego układu nerwowego, w której patogenezie istotną rolę odgrywają zaburzenia odpowiedzi immunologicznej komórkowej i humoralnej. Rola limfocytów B jest istotna w prezentacji własnych antygenów komórkom T, produkcji prozapalnych cytokin i autoprzeciwciał. W postaci pierwotnie postępującej stwardnienia rozsianego dominuje odczyn zwyrodnieniowy z aksonopatią i uszkodzeniem neuronalnym. Przeciwciało monoklonalne przeciw limfocytom B CD20 zostało zastosowane w badaniach klinicznych dotyczących postaci rzutowej (OPERA I, II i pierwotnie postępującej (ORATORIO. W postaci rzutowej wykazano istotną statystycznie redukcję rocznego wskaźnika rzutów, klinicznie potwierdzonej progresji, zmian wzmacniających się po podaniu kontrastu i zmian w sekwencji T2 w obrazowaniu metodą rezonansu magnetycznego w grupie chorych leczonych okrelizumabem w porównaniu z grupą pacjentów otrzymujących interferon beta-1a. W postaci pierwotnie postępującej stwierdzono istotną statystycznie redukcję klinicznie potwierdzonej progresji, zmian w sekwencji T2 i objętości mózgu w badaniu rezonansu magnetycznego w  grupie leczonych okrelizumabem w  stosunku do placebo. Profil bezpieczeństwa okrelizumabu był zadowalający i nie różnił się znacząco od profilu w grupach kontrolnych. Wydaje się, że wpływ leku na limfocyty B CD20 przynosi korzyść kliniczną oraz że wyniki badań III fazy mogą być podstawą do rejestracji i szerokiego stosowania okrelizumabu w praktyce klinicznej.

  18. Efficacy of D- red blood cell transfusion and rituximab therapy in autoimmune hemolytic anemia with anti-D and panreactive autoantibodies arising after hematopoietic stem cell transplant.

    Science.gov (United States)

    Minakawa, Keiji; Ohto, Hitoshi; Yasuda, Hiroyasu; Saito, Shunichi; Kawabata, Kinuyo; Ogawa, Kazuei; Nollet, Kenneth E; Ikeda, Kazuhiko

    2018-04-17

    Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies to red blood cells (RBCs), which can be panreactive and/or specific to Rh/other blood group antigens. We report a severe case of AIHA after bone marrow transplantation (BMT) due to autoanti-D triggered by reactivation of Epstein-Barr virus (EBV) infection. A combined strategy of D- RBC transfusion and administration of anti-CD20 monoclonal antibody (MoAb) resolved the hemolysis. A 33-year-old male underwent allogeneic BMT from an ABO-identical and HLA-matched unrelated male donor. Five months later, while having mild chronic graft-versus-host disease, he manifested AIHA, with a hemoglobin (Hb) level of 5.1 g/dL on AIHA Day 2 (Posttransplant Day 156) and was refractory to D+ RBCs, with a Hb level of 2.4 g/dL on AIHA Day 6. Anti-D-like autoantibodies (titer 1280, subclass immunoglobulin G 1 , monocyte monolayer assay 28.7%) and panreactive (titer 40) were identified. Changing the RBC transfusion strategy to D- increased his Hb level to 6.7 g/dL on Day 10. Administration of anti-CD20 MoAb mitigated EBV-related B-cell proliferation and reduced anti-D autoantibody titer to 320 by Day 16 with normalized Hb concentration after 6 months. In severe AIHA, when standard treatment and regular RBC transfusions are ineffective, transfusion of RBCs lacking the target antigen(s) of autoantibodies and administration of anti-CD20 MoAb should be considered. © 2018 AABB.

  19. After anti-racism?

    OpenAIRE

    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...

  20. Photon anti bunching versus phantom anti bunching?

    International Nuclear Information System (INIS)

    Miranowicz, A.; Ekert, A.; Ekert, A.; Bajer, J.; Leonski, W.

    1997-01-01

    Photon anti bunching defined by two-time correlation functions has hitherto, to our best knowledge, been considered to constitute a unique, well defined effect. We show explicitly that this is by no means the case. We analyze two of the most famous definitions showing that both anti bunching and bunching effects according to one definition can be accompanied by arbitrary photon correlation effects according to another. As an example we discuss a model of parametric frequency conversion. (authors)

  1. Anti-Vaccination Movement

    OpenAIRE

    Chapman, Jonathan

    2010-01-01

    The current anti-vaccination movements that have established themselves in the United States as well as other regions in the world are like a hydra of discourse. Right when one effective measure is created to convince people to vaccinate two more anti-vaccination movements sprout up in its place. These anti-vaccination movements are driven by cultural beliefs, ideologies, medical exemption laws, non-medical exemption laws, distrust of the government, distrust of large pharmaceutical companies...

  2. Anti-matter factory

    CERN Document Server

    Michaut, C

    2003-01-01

    In 1928 Paul Dirac predicted the existence of anti-matter as a consequence of his theory. The first experimental fact that supported this idea was the discovery of the positron in 1932. Anti-protons were produced in 1955 at the Bevatron facility in Berkeley and anti-neutrons the following year. Since 1964 scientists know that matter and anti-matter differ not only from their electrical charge but also from their behaviour concerning weak interaction. In 2002 the CERN announced the production of more than 50.000 atoms of anti-hydrogen which was a breakthrough because the last attempt in 1995 ended with the creation of only 9 atoms of anti-hydrogen whose speed neared the velocity of light while the speed of the last ones created is 100.000 times smaller. The next step is to carry out experiments in order to measure the spectra of anti-hydrogen in a very accurate manner and to test the effect of gravity on anti-matter. (A.C.)

  3. Anti-convulsants and anti-depressants.

    Science.gov (United States)

    Dickenson, A H; Ghandehari, J

    2007-01-01

    Damage to a nerve should only lead to sensory loss. While this is common, the incidence of spontaneous pain, allodynia and hyperalgesia indicate marked changes in the nervous system that are possible compensations for the loss of normal function that arises from the sensory loss. Neuropathic pain arises from changes in the damaged nerve which then alter function in the spinal cord and the brain and lead to plasticity in areas adjacent to those directly influenced by the neuropathy. The peripheral changes drive central compensations so that the mechanisms involved are multiple and located at a number of sites. Nerve damage increases the excitability of both the damaged and undamaged nerve fibres, neuromas and the cell bodies in the dorsal root ganglion. These peripheral changes are substrates for the ongoing pain and the efficacy of excitability blockers such as carbamazepine, lamotrigine and mexiletine, all anti-convulsants. A better understanding of ion channels at the sites of injury has shown important roles of particular sodium, potassium and calcium channels in the genesis of neuropathic pain. Within the spinal cord, increases in the activity of calcium channels and the receptors for glutamate, especially the N-methyl-D-aspartate (NMDA) receptor, trigger wind-up and central hyperexcitability. Increases in transmitter release, neuronal excitability and receptive field size result from the damage to the peripheral nerves. Ketamine and gabapentin/pregabalin, again with anti-convulsant activity, may interact with these mechanisms. Ketamine acts on central spinal mechanisms of excitability whereas gabapentin acts on a subunit of calcium channels that is responsible for the release of pain transmitters into the spinal cord. In addition to these spinal mechanisms of hyperexcitability, spinal cells participate in a spinal-supraspinal loop that involves parts of the brain involved in affective responses to pain but also engages descending excitatory and inhibitory

  4. Anti pp interactions in anti p atoms

    International Nuclear Information System (INIS)

    Poth, H.

    1975-01-01

    The x-rays of anti p atoms were recorded to trace out a strong interaction shift and width to the electromagnetic energy and the radiation width of the low-lying levels. The energy of the levels and consequently the energy of the transitions was calculated by solving numerically the Dirac equation with an electromagnetic potential, taking into account the finite size of the nucleus and the vacuum polarization. Due to the lack of sufficient data, the antiproton-nucleon interaction was not well understood at low energies. In order to separate antiproton-proton from antiproton-neutron interactions, the studies of isotope effects were proposed. (L.M.K.)

  5. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    Science.gov (United States)

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  6. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    International Nuclear Information System (INIS)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L.

    2004-01-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ( 9 0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ( 1 31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades

  7. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    Energy Technology Data Exchange (ETDEWEB)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L. [Calfornia Univ., Sacramento (United States). Davis Medical Center

    2004-12-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ({sup 9}0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ({sup 1}31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  8. The Anti-Landscape

    DEFF Research Database (Denmark)

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

  9. Investigation of the anti-inflammatory and anti- nociceptive activities ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-06-15

    Jun 15, 2009 ... (1998) Antinociceptive and anti-inflammatory effects of Sambucus ebulus rhizome extract in rats. J. Ethnopharmacol. 61: 229-235. Barros IMC, Lopes LDG, Borges MOR, Borges ACR, Ribeiro MNS,. Freire SMF (2006). Anti-inflammatory and anti-nociceptive activities of Pluchea quitic (D.C) ethanolic extract.

  10. Pure anti-oestrogens.

    Science.gov (United States)

    Hermenegildo, C; Cano, A

    2000-01-01

    Pure anti-oestrogens are a group of at least five new compounds which are able to antagonize the effects of oestrogen in all tissues and species studied. The mechanism by which the pure anti-oestrogens produce their effects remains in question, but all of them are competitive antagonists of the oestrogen receptors and, moreover, have been proposed to block the shuttling of oestrogen receptors into the cell nucleus. When studied in vitro, these compounds are able to block the oestrogen-stimulated growth of breast cancer cells. In animals, their ability to block the effects of oestrogen on breast, uterus, bone, cardiovascular system and other reproductive-associated tissues has been demonstrated. ICI 182780 has been used in preliminary clinical trials in women with advanced, tamoxifen-resistant breast cancer with promising results. Clinical trials with EM-800 are under way to assess the safety and tolerance and to obtain information on its efficacy in patients who have already been treated with tamoxifen. It seems reasonable to assume that pure anti-oestrogens will be a good alternative to tamoxifen in the treatment of breast cancer and also in some non-malignant gynaecological diseases.

  11. Insane anti-Membranes?

    International Nuclear Information System (INIS)

    Giecold, Gregory; Orsi, Francesco; Puhm, Andrea

    2014-01-01

    The backreactions of anti-branes on a variety of supergravity backgrounds have been shown in a recent series of papers to be riled by some unexplained flux singularities. All of the situations studied so far involve backgrounds with (close to) AdS-asymptotics. It is the purpose of this work to study the backreaction of anti-M2 branes on a background exhibiting a different UV behavior: the so-called A 8 regular solution of eleven-dimensional supergravity that we consider has “Taub-NUT type' asymptotics. As it turns out, some subleading infrared singularities are inevitable; they cannot be naturally ascribed to the anti-branes backreacting on this background. Moreover, our configuration does not involve smeared branes. This lends further credence to the work of Bena et al. http://dx.doi.org/10.1007/JHEP09(2013)142 suggesting that the singularities encountered are in no way remnants of smearing that would wash away once brane polarization is taken into account

  12. 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......The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel triplexes modified with these two monomers is determined. When, the anti...... 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...

  13. Anti-semitism and Xenophobia.

    Science.gov (United States)

    Kogan, Ilany

    2017-12-01

    This paper explores the link between anti-Semitism and xenophobia from a psychoanalytic prism. The author claims that anti-Semitism is a particular form of xenophobia directed against Jews, with some unique characteristics. She first introduces some basic notions about xenophobia, and then discusses the origins of anti-Semitism as they are viewed in early psychoanalytic thinking and in contemporary psychoanalysis. The article explores the nature of anti-Semitism in society today, and presents some reflections on the interplay between anti-Semitism and other kinds of xenophobia.

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Triply heavy tetraquark states with the QQ anti Q anti q configuration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics of CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui; Wu, Jing [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center of High Energy Physics, Beijing (China)

    2017-01-15

    In the framework of the color-magnetic interaction, we systematically investigate the mass splittings of the QQ anti Q anti q tetraquark states and estimate their rough masses in this work. These systems include the explicitly exotic states cc anti b anti q and bb anti c anti q and the hidden exotic states cc anti c anti q, cb anti b anti q, bc anti c anti q, and bb anti b anti q. If a state around the estimated mass region can be observed, its nature as a genuine tetraquark is favored. The strong decay patterns shown here will be helpful to the experimental search for these exotic states. (orig.)

  16. Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella asiatica extracts.

    Science.gov (United States)

    George, Mathew; Joseph, Lincy; Ramaswamy

    2009-07-03

    This study investigated antipruritic and anti-inflammatory effect of Centella asiatica extract in rats and anti-allergic in vitro using sheep (Capra hircus) serum method and compound 48/80 induced mast cell degranulation method, compared with standard drug ketotifen fumarate. In rats, extract of Centella asiatica administered orally was examined for anti-pruritic study and chlorpheniramine maleate was used as standard drug while carageenan paw induced inflammatory method was used for the antiinfammatory study. The results show that the extracts of Centella asiatica exhibited antiallergic, anti-pruritic and anti-inflammatory activities.

  17. The Anti-Landscape

    DEFF Research Database (Denmark)

    There have always been some uninhabitable places, but in the last century human beings have produced many more of them. These anti-landscapes have proliferated to include the sandy wastes of what was once the Aral Sea, severely polluted irrigated lands, open pit mines, blighted nuclear zones...... that no longer sustain life. This history includes T. S. Eliot’s Wasteland and Cormac McCarthy’s The Road as well as air pollution, recycled railway lines, photography and landfills. It links theories of aesthetics, politics, tourism, history, geography, and literature into the new synthesis of the environmental...

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

    Directory of Open Access Journals (Sweden)

    Anastasia Meshcheryakova

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

  19. High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma.

    Science.gov (United States)

    Morschhauser, Franck; Kraeber-Bodéré, Françoise; Wegener, William A; Harousseau, Jean-Luc; Petillon, Marie-Odile; Huglo, Damien; Trümper, Lorenz H; Meller, Johannes; Pfreundschuh, Michael; Kirsch, Carl-Martin; Naumann, Ralph; Kropp, Joachim; Horne, Heather; Teoh, Nick; Le Gouill, Steven; Bodet-Milin, Caroline; Chatal, Jean-Francois; Goldenberg, David M

    2010-08-10

    Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

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

    Directory of Open Access Journals (Sweden)

    Jakub Bogusz

    2013-03-01

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

  1. [Anti-N-methyl-D aspartate receptor encephalitis - guideline to the challenges of diagnosis and therapy].

    Science.gov (United States)

    Hau, Lídia; Csábi, Györgyi; Tényi, Tamás

    2015-01-01

    Anti-N-methyl-D-Aspartate encephalitis is a recently diagnosed autoimmune disorder with increasing significance. During this disease antibodies are produced against the subunit of the NMDA receptor, which cause different symptoms, both psychiatric and neurological. The aim of this publication is to introduce this disease, to facilitate the diagnosis and to recommend therapeutical guideline. In this review we summarized the relevant literature published between 2007 and 2015 giving emphasis on etiopathogenesis, diagnosis, differential diagnosis, treatment and prognosis. In the etiology an underlying tumor or a viral agent should be considered. During the disease we can discern 3 periods: first prodromal viral infections-like symptoms can be seen, 1-2 weeks later psychiatric symptoms, such as aggression, sleep and behavior disturbances appear. After that neurological symptoms (tonic-clonic convulsions, aphasia, catatonia, orofacial dyskinesia, autonom lability, altered mental state) are typical, and the patient's condition deteriorates. For the correct diagnosis it is necessary to detect antibodies against the NMDA receptor from the serum and the liquor. Steroids, immunoglobulins and plasmaheresis are the first-line therapies. If the disease is unresponsive, then as a second-line therapy anti-CD 20 (Rituximab) and cyclophosphamid can be useful. Most of the patients are improving without any neurological sequale with prompt detection and appropriate therapy. It is important to be familiar with the symptoms, diagnosis and therapy of this disease as a practicing clinician, especially as a psychiatrist or neurologist. 75 percentage of the patients are admitted to psychiatric departments first because of the leading symptoms. Autoimmune NMDA encephalitis is a reversible disease after early diagnosis and treatment.

  2. Anti-vibration gloves?

    Science.gov (United States)

    Hewitt, Sue; Dong, Ren G; Welcome, Daniel E; McDowell, Thomas W

    2015-03-01

    For exposure to hand-transmitted vibration (HTV), personal protective equipment is sold in the form of anti-vibration (AV) gloves, but it remains unclear how much these gloves actually reduce vibration exposure or prevent the development of hand-arm vibration syndrome in the workplace. This commentary describes some of the issues that surround the classification of AV gloves, the assessment of their effectiveness and their applicability in the workplace. The available information shows that AV gloves are unreliable as devices for controlling HTV exposures. Other means of vibration control, such as using alternative production techniques, low-vibration machinery, routine preventative maintenance regimes, and controlling exposure durations are far more likely to deliver effective vibration reductions and should be implemented. Furthermore, AV gloves may introduce some adverse effects such as increasing grip force and reducing manual dexterity. Therefore, one should balance the benefits of AV gloves and their potential adverse effects if their use is considered. © Crown copyright 2014.

  3. Anti-sulfotyrosine antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R [Berkeley, CA; Kehoe, John [Saint Davids, PA; Bradbury, Andrew M [Santa Fe, NM

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  4. anti p and anti Λ production in Si+Au collisions at the AGS

    International Nuclear Information System (INIS)

    Wu, Yuedong

    1996-01-01

    Anti p and anti Λ production in central Si + Au collisions has been measured by E589 at the BNL-AGS. Preliminary m perpendicular spectra are presented for anti p's and anti Λ's. The dn/dy distribution for anti p's is also presented. Based on the anti p and anti Λ measurements, anti Λ/anti p ratios are calculated in the rapidity range of 1.1-1.5

  5. Calculations of anti pp → anti yy near threshold

    International Nuclear Information System (INIS)

    Eisenstein, R.A.

    1982-01-01

    The reactions anti pp → anti yy will soon be studied near threshold at LEAR. Comparison of theoretical calculations with the measured differential cross sections, polarizations and spin correlations may help to determine the role of various meson exchange terms and the extent to which quark degrees of freedom are important. Calculations along these lines are in progress and are described briefly

  6. Reviews Evaluating the Anti-Plasmodium, Anti-Pyretic and ...

    African Journals Online (AJOL)

    Discovery and Innovation ... With the introduction of cheap anti-malaria drugs, there was marked reduction in the use of local herbal medicine. ... Key Words: medicinal plants, local traditional medicine, malaria, anti-malarial properties, antipyretic and analgesic properties, concoctions, efficacy, resistance, generic ...

  7. Anti-Hyperglycemic And Anti-Hyperlipidemic Potential Of A ...

    African Journals Online (AJOL)

    Conclusion: Our study suggests that diabegon could be included as a preventive treatment in metabolic syndrome subjects with type 2 diabetes especially for long term treatment as it efficiently shows anti-hyperglycemic and anti-lipidemic effects with no adverse impacts on the liver and kidney. Key words: Metabolic ...

  8. Television and Anti-Racism.

    Science.gov (United States)

    Ali, Yasmin

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

  9. Charmed meson rescattering in the reaction anti pd→ anti DDN

    International Nuclear Information System (INIS)

    Haidenbauer, J.; Krein, G.; Meissner, U.G.; Sibirtsev, A.

    2008-01-01

    We examine the possibility to extract information about the DN and anti DN interactions from the anti pd→D 0 D - p reaction. We utilize the notion that the open-charm mesons are first produced in the annihilation of the antiproton on one nucleon in the deuteron and subsequently rescatter on the other (the spectator) nucleon. The latter process is then exploited for investigating the DN and anti DN interactions. We study different methods for isolating the contributions from the D 0 p and D - p rescattering terms. (orig.)

  10. Anti-nuclear movements

    International Nuclear Information System (INIS)

    Ruedig, W.

    1990-01-01

    Nuclear power, heralded in the years after World War II as the answer to the world's energy needs, has in more recent times become the focus of intense ecological, political and economic debate. In this study, the current worldwide opposition to nuclear power is examined from its origins in expert dissent to the widespread development of grassroots activity. Chapter headings include: Social Movements: A Theoretical Framework; Creating the Preconditions for Public Protest; Local and Regional Opposition: Mobilizing the Grass Roots; Local Opposition and the Politicization of Nuclear Power; The Use of Local Opposition as a Political Resource; Local Opposition and Social Movement Analysis; The Removal of Political Stimuli: The Unpolitics of Nuclear Siting; Analyzing Host Community Attitudes: The Survey Evidence; Attitudes and Political Action of Nuclear Host Communities: Approaches and Explanations; Novel Siting Approaches and their Political Implications; Siting and Social Movement Analysis; Patterns and Outcomes of Nuclear Energy Conflicts; The Future of the Nuclear Energy Conflict. Throughout the text, analysis and theory are blended with detailed accounts of the growth and activities of individual anti-nuclear organizations in different countries. (author)

  11. Anti-diarrheal, anti-secretory, anti-spasmodic and antiulcer activities of

    African Journals Online (AJOL)

    In isolated tissue (rabbit jejunum), Am.Cr concentration-dependently (0.01 - 3.0 mg/mL) produced relaxation of K+ (80 mM)-induced and spontaneous contractions at ... anti-secretory, antispasmodic and anti-ulcer activities, probably mediated through dual mechanisms, including Ca2+ influx and PDE enzyme(s) inhibition.

  12. Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella ...

    African Journals Online (AJOL)

    This study investigated antipruritic and anti-inflammatory effect of Centella asiatica extract in rats and anti-allergic in vitro using sheep (Capra hircus) serum method and compound 48/80 induced mast cell degranulation method, compared with standard drug ketotifen fumarate. In rats, extract of Centella asiatica administered ...

  13. What is it really? Anti-G or Anti-D plus Anti-C: Clinical Significance in Antenatal Mothers.

    Science.gov (United States)

    Das, Soumya; Shastry, Shamee; Murugesan, M; B, Poornima Baliga; Shastry, Shamee

    2017-06-01

    G antigen of Rh blood group system is present either along with D and/or C positive red cells. Hence, [serologically anti-G presents with the similar picture as that of multiple antibodies (anti-D + anti-C). Differentiating them is important as anti-D + anti-C causes severe hemolytic disease of the fetus and newborn than anti-G. In pregnancies with anti-G alone, alloimmunization due to D antigen could be prevented by prophylactic administration of RhIg. Differentiating between anti-D + C from anti-G in alloimmunized pregnant mothers becomes essential. Sera from antenatal mothers, whose antibody identification by 11-cell panel gave a pattern for anti-D and anti-C were selected. Extended phenotyping for Rh system was performed for these antenatal cases. Differential adsorption and elution testing using R 2 R 2 cells initially and r'r cells subsequently were performed to distinguish anit-G from anti-D + anti-C. Antibody titers of these antibodies were determined and their clinical outcome in the newborn was followed. A pattern suggestive of anti D and anti C on antibody identification were observed in six antenatal cases. On further workup 50 % of them confirmed to have anti G. Antibody titers of anti-G and anti-C were lower than that of Anti-D. All newborns were sensitized in vivo and the antibody specificity in them were confirmed with elution studies. The mothers who had only anti-G were subsequently administered with an appropriate dose of RhIg.Differential adsorption and elution studies help in identifying anti-G and distinguishing it from anti-D plus anti-C, thus helping in better patient management.

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

    International Nuclear Information System (INIS)

    Maher, C.J.

    1986-06-01

    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

  15. 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...

  16. 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.

  17. Anti-C.Diff Pill

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Anand [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-01-30

    The anti- C.diff pill is being developed for patients who are at high risk for Clostridium difficile, a bacterium that causes diarrhea and serious intestinal conditions like colitis. C-diff is deadly, killing over 30,000 people a year in the United States and costing an average of $42,000 per treatment. The most common treatment is a fecal transplant (FT). The anti- C.diff replaces the invasive and messy FT practice with a pill.

  18. Approach to a Pregnant Woman with Anti D + Anti C Reactivity Pattern: A Diagnostic Conundrum.

    Science.gov (United States)

    Rai, Preeti; Sharma, Geetika; Singh, Deeksha; Garg, Jyoti

    2017-09-01

    The Rhesus G antigen is present on all RBCs that are C+ and also on most D+ RBCs. Due to this co-distribution of G with either C or D antigen, it mimics a reactivity pattern of anti C + anti D on Indirect Antiglobulin Test (IAT), though the role of Anti G in causing Hemolytic Disease of Newborn (HDN) is controversial. The differentiation of anti D, anti C, and anti G is essential particularly in pregnant females. We hereby report a rare case of anti G with anti D and anti C in a pregnant woman with emphasis on approach to identify anti D+C+G and its implications.

  19. Anti-human SIRPα antibody is a new tool for cancer immunotherapy.

    Science.gov (United States)

    Murata, Yoji; Tanaka, Daisuke; Hazama, Daisuke; Yanagita, Tadahiko; Saito, Yasuyuki; Kotani, Takenori; Oldenborg, Per-Arne; Matozaki, Takashi

    2018-02-23

    Interaction of signal regulatory protein α (SIRPα) expressed on the surface of macrophages with its ligand CD47 expressed on target cells negatively regulates phagocytosis of the latter cells by the former. We recently showed that blocking Abs to mouse SIRPα enhanced both the Ab-dependent cellular phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in nonobese diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRPα in preclinical cancer models have remained unclear given that such Abs have failed to interact with endogenous SIRPα expressed on macrophages of immunodeficient mice. With the use of Rag2 -/- γ c -/- mice harboring a transgene for human SIRPα under the control of human regulatory elements (hSIRPα-DKO mice), we here show that a blocking Ab to human SIRPα significantly enhanced the ADCP activity of macrophages derived from these mice for human cancer cells. The anti-human SIRPα Ab also markedly enhanced the inhibitory effect of rituximab on the growth of tumors formed by Raji cells in hSIRPα-DKO mice. Our results thus suggest that the combination of Abs to human SIRPα with therapeutic Abs specific for tumor antigens warrants further investigation for potential application to cancer immunotherapy. In addition, humanized mice, such as hSIRPα-DKO mice, should prove useful for validation of the antitumor effects of checkpoint inhibitors before testing in clinical trials. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

    Science.gov (United States)

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

    2017-07-01

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

  1. Approach to a Pregnant Woman with Anti D + Anti C Reactivity Pattern: A Diagnostic Conundrum

    OpenAIRE

    Rai, Preeti; Sharma, Geetika; Singh, Deeksha; Garg, Jyoti

    2017-01-01

    The Rhesus G antigen is present on all RBCs that are C+ and also on most D+ RBCs. Due to this co-distribution of G with either C or D antigen, it mimics a reactivity pattern of anti C + anti D on Indirect Antiglobulin Test (IAT), though the role of Anti G in causing Hemolytic Disease of Newborn (HDN) is controversial. The differentiation of anti D, anti C, and anti G is essential particularly in pregnant females. We hereby report a rare case of anti G with anti D and anti C in a pregnant woma...

  2. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells...

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

    Directory of Open Access Journals (Sweden)

    Rabeya Yousuf

    2017-01-01

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

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

    Science.gov (United States)

    Yousuf, Rabeya; Mustafa, Ahmad Nasirudin; Ho, Siew-Ling; Tang, Yee-Loong; Leong, Chooi-Fun

    2017-01-01

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

  5. Anti-inflammatory, Anti-estrogenic, and Anti-implantation Activity of Bergia suffruticosa (Delile) Fenzl

    Science.gov (United States)

    Bind, Sandeep Kumar; Jivrajani, Mehul; Anandjiwala, Sheetal; Nivsarkar, Manish

    2015-01-01

    Background: Bergia suffruticosa (Delile) Fenzl (Syn. Bergia odorata Edgew) (Elatinaceae family) is used traditionally to repair bones and is applied as a poultice on sores. It is also used for stomach troubles and as an antidote to scorpion stings. So far, very little scientific work has been reported to validate its ethnomedical uses in the alleviation of pain, bone repair, etc., Objective: This study was designed to explore the anti-inflammatory and anti-implantation potential of n-hexane extract of B. suffruticosa whole plant in mice along with identification of its chemical constituents. Materials and Methods: n-Hexane extract of B. suffruticosa whole plant was screened for acute and chronic anti-inflammatory activity followed by an anti-estrogenic activity. Eventually, n-hexane extract was tested for anti-implantation activity by exploiting markers of uterine receptivity, lipid peroxidation, and superoxide enzyme activity. The extract was administered orally at a dose of 100 mg/kg body weight in each study. Results: Thin layer chromatography fingerprint profile of n-hexane extract revealed the presence of lupeol and β-sitosterol. The n-hexane extract reduced the edema by 80% in acute inflammation, whereas it reduced edema to 75% on the 5th day in chronic inflammation. The n-hexane extract reduced elevated malonaldehyde level from 6 to 2.5 nmol/g × 10−5 and increased superoxide dismutase enzyme activity from 0 to 350 units/g in treated animals on the 5th day of pregnancy. Moreover, extract decreased uterine weight from 0.33 to 0.2 g in estradiol treated animals. Conclusion: These results indicate that n-hexane extract of B. suffruticosa is having potent anti-inflammatory, anti-estrogenic, and anti-implantation activity. This is the first report of all the pharmacological activities of B. suffruticosa mentioned above. SUMMARY TLC fingerprint profile of n-hexane extract of Bergia suffruticosa whole plant revealed the presence of lupeol and

  6. Antioxidant, anti-inflammatory and anti-nociceptive properties of ...

    African Journals Online (AJOL)

    The anti-inflammatory potential was investigated in egg-albumin and carrageenan induced paw edema models while the antinociceptive activity was determined using acetic acid induced writhing reflex and tail immersion tests at the doses of 50, 100 and 200 mg/kg. The negative control group (group A) received distilled ...

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

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2013-12-01

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

  8. Evaluation of the anti-inflammatory Evaluation of the Anti ...

    African Journals Online (AJOL)

    The anti-inflammatory activity of the aqueous leaf extract of Pterocarpus santalinoides was evaluated using the carrageenan-induced paw oedema and leucocyte migration in rats, and croton oil-induced ear oedema in mice. The extract (50-100mg/kg) and indomethacin (10mg/kg) produced significant (p<0.05) inhibitions of ...

  9. Synthesis, Anti-inflammatory and Anti-nociceptive Evaluation of ...

    African Journals Online (AJOL)

    The final products were purified on column chromatography, eluting with ... the reference drug. Results: The compounds were obtained in high yield (70 – 90 %) and purity. The anti-inflammatory results showed a poor activity for the compounds except o-palmitoylamino ..... causes an increase in the peritoneal fluid level of.

  10. Anti-inflammatory, anti-nociceptive and antipyretic potential of ...

    African Journals Online (AJOL)

    Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity.

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

    Science.gov (United States)

    Lançon, Allan; Frazzi, Raffaele; Latruffe, Norbert

    2016-03-02

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

  12. 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.

  13. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  14. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  15. Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties.

    Science.gov (United States)

    Lee, Jin-Ching; Hou, Ming-Feng; Huang, Hurng-Wern; Chang, Fang-Rong; Yeh, Chi-Chen; Tang, Jen-Yang; Chang, Hsueh-Wei

    2013-06-03

    For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from marine algae protect cells by modulating the effects of oxidative stress. Because oxidative stress plays important roles in inflammatory reactions and in carcinogenesis, marine algal natural products have potential for use in anti-cancer and anti-inflammatory drugs.

  16. Model independent calculation of B(anti B0→D(*)+τ- anti ν)/B(anti B0→D(*)+e- anti ν)

    International Nuclear Information System (INIS)

    Hwang, D.S.

    2000-01-01

    Using the formulas for the dΓ/dq 2 distribution with non-zero lepton mass and experimentally determined form factors, we calculate the dΓ(D (*)+ l - anti ν)/dq 2 spectra and branching fractions for l=e,μ and τ. We obtain the results B(anti B 0 →D + τ - anti ν)/B(anti B 0 →D + e - anti ν)=0.278 +0.049 -0.035 and B(anti B 0 →D *+ τ - anti ν)/B(anti B 0 →D *+ e - anti ν)=0.256 +0.014 -0.013 . Since we used the experimentally measured form factors, these results are independent of theoretical models of the form factors. (orig.)

  17. [Guideline for radioimmunotherapy of CD20+ follicular B-cell non-Hodgkin's lymphoma].

    Science.gov (United States)

    Fischer, M; Grünwald, F; Knapp, W H; Trümper, L; von Schilling, C; Dreyling, M

    2009-01-01

    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, radioimmunotherapy under consideration of the development of the disease.

  18. Equilibrated anti-Monge Matrices

    Czech Academy of Sciences Publication Activity Database

    Fiedler, Miroslav

    2001-01-01

    Roč. 335, - (2001), s. 151-156 ISSN 0024-3795 R&D Projects: GA ČR GA201/98/0222 Institutional research plan: AV0Z1030915 Keywords : Monge matrix * anti-Monge matrix Subject RIV: BA - General Mathematics Impact factor: 0.423, year: 2001

  19. EAMJ Feb. Anti.indd

    African Journals Online (AJOL)

    East African Medical Journal Vol. 86 No. 2 February 2009. ANTI-PHOSPHOLIPID SYNDROME: IN NIGERIA: REPORT OF FIVE CASES. O.O., Adelowo, MBBS (1b), FMCP, FWACP, FACR, Professor of Medicine and Consultant Rheumatologist and S. Oguntona,. MBChB, FWACP, Lecturer and Consultant Physician, ...

  20. On Mathematical Anti-Evolutionism

    Science.gov (United States)

    Rosenhouse, Jason

    2016-01-01

    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…

  1. Pendidikan Anti Korupsi Berbasis Agama

    Directory of Open Access Journals (Sweden)

    Kasinyo Harto

    2016-03-01

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

  2. Production of d, t, 3He, anti d, anti t and anti 3He by 200 GeV protons

    International Nuclear Information System (INIS)

    Bozzoli, W.; Giacomelli, G.; Rimondi, F.; Zylberajch, S.; Lesquoy, E.; Meunier, R.; Moscoso, L.; Muller, A.; Bussiere, A.

    1978-01-01

    Data are presented on the yields of d, t, 3 He, anti d, anti t, and anti 3 He with laboratory momenta between 12 and 37 GeV/c produced by 200 GeV protons on beryllium and aluminium. The production yield of nuclei depends significantly on the target nucleus, while the anti d production is independent of target material. The mass dependence of the production cross section is exponential for both nuclei and antinuclei

  3. Anti- versus Pro-Competitive Mergers

    OpenAIRE

    Fridolfsson, Sven-Olof

    2007-01-01

    In a framework where mergers are mutually excluding, I show that firms pursue anti- rather than (alternative) pro-competitive mergers. Potential outsiders to anti-competitive mergers refrain from pursuing pro-competitive mergers if the positive externalities from anti-competitive mergers are strong enough. Potential outsiders to pro-competitive mergers pursue anti-competitive mergers if the negative externalities from the pro-competitive mergers are strong enough. Potential participants in an...

  4. Biological anti-TNF drugs

    DEFF Research Database (Denmark)

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-01-01

    is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review...... provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune......-biological drugs is helpful when evaluating patients with secondary failure. However, immunological tests for ADA vary considerably regarding their ability to detect different types of ADA. Several assays are not designed to determine ADA-induced drug neutralizing capacity, and they may report clinically non...

  5. Brane - Anti-Brane Democracy

    Energy Technology Data Exchange (ETDEWEB)

    Rajaraman, Arvind

    2003-06-02

    We suggest a duality invariant formula for the entropy and temperature of nonextreme black holes in supersymmetric string theory. The entropy is given in terms of the duality invariant parameter of the deviation from extremality and 56 SU(8) covariant central charges. It interpolates between the entropies of Schwarzschild solution and extremal solutions with various amount of unbroken supersymmetries and therefore serves for classification of black holes in supersymmetric string theories. We introduce the second auxiliary 56 via E(7) symmetric constraint. The symmetric and antisymmetric combinations of these two multiplets are related via moduli to the corresponding two fundamental representations of E(7): brane and anti-brane ''numbers.'' Using the CPT as well as C symmetry of the entropy formula and duality one can explain the mysterious simplicity of the non-extreme black hole area formula in terms of branes and anti-branes.

  6. 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 that the use of theranostics (i.e., monitoring circulating levels of functional anti-TNF-α drugs and antidrug antibodies) would markedly improve treatment because therapies can be tailored to individual patients and provide more effective and economical long-term therapies with minimal risk of side effects....... Large-scale immunopharmacological knowledge of how patients 'handle' TNF-α biopharmaceuticals would also help industry develop more effective and safer TNF-α inhibitors....

  7. 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...

  8. Anti-leukotriene therapy in asthma

    NARCIS (Netherlands)

    Diamant, Z.; Bel, E. H.; Dekhuijzen, P. N.

    1998-01-01

    There is ample evidence that leukotrienes are important inflammatory mediators of asthma. Anti-leukotriene therapy is a novel, specific anti-asthma strategy providing both reliever and controller effects. Currently, two types of anti-leukotriene drugs are being registered in several countries:

  9. Corruption and Anti-Corruption

    OpenAIRE

    Larmour, Peter; Wolanin, Nick

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chao Lien Liu

    2016-06-01

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

  11. Partial wave analysis of anti pp → anti ΛΛ

    International Nuclear Information System (INIS)

    Bugg, D.V.

    2004-01-01

    A partial wave analysis of PS185 data for anti pp → anti ΛΛ is presented. A 3 S 1 cusp is identified in the inverse process anti ΛΛ→ anti p p at threshold, using detailed balance to deduce cross sections from anti pp → anti ΛΛ. Partial wave amplitudes for anti pp 3 P 0 , 3 F 3 , 3 D 3 and 3 G 3 exhibit a behaviour very similar to resonances observed in Crystal Barrel data. With this identification, the anti pp → anti ΛΛ data then provide evidence for a new I=0, J PC =1 - resonance with mass M = 2290 ±20 MeV, Γ= 275 ±35 MeV, coupling to both 3 S 1 and 3 D 1 . (orig.)

  12. Exotic tetraquark states with the qq anti Q anti Q configuration

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Si-Qiang; Chen, Kan; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics, CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Liu, Yan-Rui [Shandong University, School of Physics and Key Laboratory of Particle Physics and Particle Irradiation (MOE), Jinan (China); Zhu, Shi-Lin [Peking University, School of Physics and State Key Laboratory of Nuclear Physics and Technology, Beijing (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Peking University, Center for High Energy Physics, Beijing (China)

    2017-10-15

    In this work, we study systematically the mass splittings of the qq anti Q anti Q (q = u, d, s and Q = c, b) tetraquark states with the color-magnetic interaction by considering color mixing effects and estimate roughly their masses. We find that the color mixing effect is relatively important for the J{sup P} = 0{sup +} states and possible stable tetraquarks exist in the nn anti Q anti Q (n = u, d) and ns anti Q anti Q systems either with J = 0 or with J = 1. Possible decay patterns of the tetraquarks are briefly discussed. (orig.)

  13. Nanostructured surfaces for anti-biofouling/anti-microbial applications

    Science.gov (United States)

    Choi, Chang-Hwan; Kim, Chang-Jin

    2009-05-01

    Recent nanotechnology revolutions have cast increased challenges to biotechnology including bio-adhesion of cells. Surface topography and chemistry tailored by the nanotechnology exert significant effects on such applications so that it is necessary to understand how cells migrate and adhere on three-dimensional micro- and nanostructures. However, the effects of the surface topography and chemistry on cell adhesions have not been studied systematically and interactively yet mostly due to the inability to create well-controlled nanostructures over a relatively large surface area. In this paper, we report on the bio-adhesions of varying cell types on well-ordered (post and grate patterns), dense-array (230 nm in pattern periodicity), and sharp-tip (less than 10 nm in tip radius) nanostructures with varying three-dimensionalities (50- 500 nm in structural height). Significantly lower cell proliferation and smaller cell size were measured on tall nanostructures. On a grate pattern, significant cell elongation and alignment along the grate pattern were observed. On tall nanostructures, it was shown that cells were levitated by sharp tips and easily peeled off, suggesting that cell adherence to the tall and sharp-tip nanostructures was relatively weak. The control of cell growth and adherence by the nanoscale surface topographies can benefit the micro- and nanotechnogies-based materials, devices, and systems, such as for anti-biofouling and anti-microbial surfaces. The obtained knowledge by this investigation will also be useful to deal with engineering problems associated with the contact with biological substances such as biomaterials and biosensors.

  14. Investigation of the decays anti B0 → D*+l-anti ν and anti B → D**l-anti ν

    International Nuclear Information System (INIS)

    Albrecht, H.; Ehrlichmann, H.; Hamacher, T.; Hofmann, R.P.; Kirchhoff, T.; Nau, A.; Nowak, S.; Schroeder, H.; Schulz, H.D.; Walter, M.; Wurth, R.; Appuhn, R.D.; Hast, C.; Kolanoski, H.; Lange, A.; Lindner, A.; Mankel, R.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Toepfer, D.; Walther, A.; Wegener, D.; Britton, D.I.; Charlesworth, C.E.K.; Edwards, K.W.; Hyatt, E.R.F.; Kapitza, H.; Krieger, P.; MacFarlane, D.B.; Patel, P.M.; Prentice, J.D.; Saull, P.R.B.; Tzamariudaki, K.; Van de Water, R.G.; Yoon, T.S.; Ressing, D.; Schmidtler, M.; Schneider, M.; Schubert, K.R.; Strahl, K.; Waldi, R.; Weseler, S.

    1993-01-01

    Exclusive semileptonic B decays with a D *+ meson in the final state have been studied using the ARGUS detector at the DORIS II storage ring. The branching ratio for the decay anti B 0 →D *+ l - anti ν, where l - is either e - or μ - , has been measured to be (5.2±0.5±0.6)%. A significant rate for the decay anti B→D ** l - anti ν has been observed. From an angular analysis of the cascade anti B 0 →D *+ (→D 0 π + )l - anti ν the forward-backward asymmetry A FB and the D *+ polarization parameter α have been determined to be A FB =0.20±0.08±0.06 and α=1.1±0.4±0.2. (orig.)

  15. Multinationals and Anti-sweatshop Activism

    OpenAIRE

    Harrison, Ann; Scorse, Jason

    2010-01-01

    During the 1990s, anti-sweatshop activists campaigned to improve conditions for workers in developing countries. This paper analyzes the impact of anti-sweatshop campaigns in Indonesia on wages and employment. Identification is based on comparing the wage growth of workers in foreign-owned and exporting firms in targeted regions or sectors before and after the initiation of anti-sweatshop campaigns. We find the campaigns led to large real wage increases for targeted enterprises. There were so...

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

    Directory of Open Access Journals (Sweden)

    Yousuf Rabeya

    2012-02-01

    Full Text Available 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 born to a mother who was group A RhD negative. The baby was jaundiced with hyperbilirubinemia, but with no evidence of infection. His blood group was group A RhD positive, his direct Coombs' test result was positive and red cell elution studies demonstrated the presence of anti-D and anti-S alloantibodies. Investigations performed on the maternal blood during the 22 weeks of gestation showed the presence of anti-S antibodies only. Repeat investigations performed post-natally showed the presence of similar antibodies as in the newborn and an anti-D titer of 1:32 (0.25 IU/mL, which was significant. A diagnosis of hemolytic disease of the fetus and newborn secondary to anti-D and anti-S was made. The baby was treated with phototherapy and close monitoring. He was discharged well after five days of phototherapy. Conclusions This case illustrates the possibility of an anamnestic response of allo-anti-D from previous sensitization in a RhD-negative mother, or the development of anti-D in mid-trimester. Thus, it highlights the importance of thorough antenatal ABO, RhD blood grouping and antibody screening, and if necessary, antibody identification and regular monitoring of antibody screening and antibody levels for prevention or early detection of hemolytic disease of the fetus and newborn, especially in cases of mothers with clinically significant red cell alloantibody.

  17. PERILAKU ANTI SOSIAL PADA ANAK SEKLOAH DASAR

    Directory of Open Access Journals (Sweden)

    Ratna Sari Dewi

    2015-09-01

    Full Text Available Perilaku Anti Sosial merupakan perilaku negatif atau perilaku yang menyimpang dari norma-norma, baik aturan keluarga, sekolah, masyarakat, maupun hukum. Jenis perilaku anti sosial pada anak sekolah dasar diantaranya perilaku negativisme, agresi dan tingkah laku menguasai. Faktor risiko yang menyebabkan perilaku anti sosial pada anak-anak dapat dikategorikan sebagai faktor pribadi (personal risk factors, keluarga (family risk factors, berkaitan dengan sekolah (school-related risk factors dan sosial (social risk factors. Upaya penanganan anak dengan anti sosial dapat dilakukan dengan upaya orang tua menerapkan pola asuh authoritative. Jika terlanjur berperilaku anti sosial pada taraf melanggar hukum negara, maka orang tua harus membawa anaknya untuk melakukan terapi gangguan kepribadian, yang disebut Terapi Perilaku Dialektikal. Sedangkan yang dapat diupayakan guru dalam menangani anak anti sosial adalah dengan menerapkan metode pembelajaran kooperatif serta memberikan perhatian Psikologi dan Perkembangan Multiple Intelegensi Anak. Selain itu masyarakat dapat memberikan kontribusi dalam penanganan anak anti sosial dengan cara menumbuhkan norma sosial yang baik serta tersedianya tayangan media massa yang memberikan tuntunan baik bagi anak.Kata Kunci : Anti – Sosial, Kooperatif, Multiple IntelegensiAnti-social behavior is a negative behavior or deviates behavior  from the norms, a good rule of family, school, community, or the law. The type of anti-social behavior in elementary school children including negativism behavior, aggression and behavioral controls. The risk factors that lead to anti-social behavior in children can be categorized as personal factors (personal risk factors, family (family risk factors, related to the school (school-related risk factors and social (social risk factors. Efforts to tackle anti-social child can do with the efforts of parents to apply parenting authoritative. If already at the level of anti-social behavior in

  18. Anti-neutrino disintegration of the deuteron

    International Nuclear Information System (INIS)

    Mueller, W.; Gari, M.; Max-Planck-Institut fuer Chemie

    1981-01-01

    The anti-neutrino disintegration of the deuteron (anti ν + D → anti ν + n + p and anti νsub(e) + D → + e + + n + n) is calculated using realistic two-body states. Meson-exchange currents are considered in the one-boson-exchange limit. The results are discussed as corrections to the cross sections obtained in effective range approximations. It is shown that the ratio of the cross sections (sigma - /sigma 0 ) for reactor antineutrinos is practically independent of the nuclear physics uncertainties. (orig.)

  19. 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.

  20. Immunodeficiency secondary to anti-cytokine autoantibodies

    Science.gov (United States)

    Browne, Sarah K.; Holland, Steven M.

    2011-01-01

    Purpose of review Anti-cytokine autoantibodies are an important and emerging mechanism of disease pathogenesis. We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anti-cytokine autoantibodies. Recent findings A growing number of patients have been described who demonstrate unique infectious phenotypes associated with neutralizing autoantibodies that target a particular cytokine known to participate in host defense against the offending organism. Examples include anti-granulocyte macrophage-colony stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti-interferon(IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria(NTM); anti-(interleukin)IL-6 autoantibodies and severe staphylococcal skin infection; anti-IL-17A, antiIL-17F or anti-IL-22 autoantibodies in patients with mucocutaneous candidiasis in the setting of both the autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome and in cases of thymoma. Summary Anti-cytokine autoantibodies have manifestations that are diverse, ranging from asymptomatic to life-threatening. These emerging and fascinating causes of acquired immunodeficiency may explain some previously idiopathic syndromes. PMID:20966748

  1. Development of Anti-G, Anti-C and Anti-Jk(b) in a 22-Year-Old Mother during Her Fourth Pregnancy.

    Science.gov (United States)

    Schulze, Torsten J; Goebel, Meike; Scharberg, Erwin A; Bugert, Peter; Janetzko, Karin

    2013-06-01

    Anti-G antibodies are rarely found since anti-D, in combination with anti-C, are difficult to discriminate from anti-G antibodies in routine testing. A 22-year-old, gravida-3, para-1, woman with blood group A Rh D neg ccddee and known antibody anti-Jk(b), gave birth to her second child. While anti-Jk(b) could not be detected at birth, a new anti-C was found. Antibody screening tests (IAT) were performed using gel cards and rare G positive rGr erythrocytes. Genotyping for RHD and RHCE was performed using PCR-SSP. The child's blood group was A Rh D neg Ccddee. Genotyping revealed Cde/cde haplotypes. The erythrocytes of the new-born showed a positive direct antiglobulin test with IgG; anti-D and anti-C could be eluted. Erythrocytes with the rare phenotype rGr were reactive with the serum of the mother. The presence of anti-D and anti-C in the eluate from then newborn's Ccddee erythrocytes proved anti-G or anti-G in combination with anti-D. When anti-C and anti-D are seen during a pregnancy, possibly anti-G is present. This observation is of relevance since women with anti-G can still develop anti-D and require rhesus prophylaxis.

  2. 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...

  3. Anti-depressants and suicide.

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E; Norberg, Karen

    2009-05-01

    Suicide takes the lives of around a million people each year, most of whom suffer from depression. In recent years there has been growing controversy about whether one of the best-selling anti-depressants - selective serotonin reuptake inhibitors (SSRIs) - increases or decreases the risk of completed suicide. Randomized clinical trials are not informative in this application because of small samples and other problems. We present what we believe are the most scientifically credible estimates to date on how SSRI sales affect suicide mortality using data from 26 countries for up to 25 years. We exploit just the variation in SSRI sales that can be explained by institutional differences in how drugs are regulated, priced, and distributed, as reflected by the sales growth of new drugs more generally. We find an increase in SSRI sales of 1 pill per capita (12% of 2000 sales levels) reduces suicide by 5%.

  4. 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...

  5. The anti-nuclear disinformation

    International Nuclear Information System (INIS)

    Gay, Michel

    2013-01-01

    After having briefly identified the origin of anti-nuclear disinformation in France in the ecologist movement, the author recalls the very different information that were spread after the Chernobyl accident, and how some aspects were immediately exploited by antinuclear ecologists. He also comments the various information and data which were published on this accident during the following years, notably about the victims, casualties and health impacts. He comments data published by international and French bodies or agencies (Nuclear Energy Agency, UNSCEAR, InVS). He outlines a continuous practice of disinformation by media, notably about wastes, evokes the consequences in terms of safety, risks and risk perception. He finally browses several issues related to the Fukushima accident

  6. 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

  7. 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.

  8. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem

    OpenAIRE

    Bhesh Raj Sharma; Chul Min Park; Jong Choi; Dong Young Rhyu

    2017-01-01

    Objective: Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). Materials and Methods: The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular...

  9. Analgesic, anti-inflammatory and anti-ulcer activities of Sida acuta in ...

    African Journals Online (AJOL)

    The analgesic, anti-inflammatory and anti-ulcer properties was also studied in mice and rats using the tail immersion, mouse ear oedema and acetylsalicylic acid induced ulceration models. The crude extracts exhibited significant (p< 0.001) analgesic and anti-inflammatory activities in mice as well as a marked protection ...

  10. Anti-oxidant and anti-inflammatory effects of rice bran and green tea ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-inflammatory and anti-oxidant properties of an enzyme bath of Oryza sativa (rice bran) and Camellia sinensis O. Kuntz (green tea) fermented with Bacillus subtilis (OCB). Methods: The anti-oxidant effects of OCB were assessed by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay and flow ...

  11. In vivo and in vitro Anti-fertility and Anti-implantation Properties of ...

    African Journals Online (AJOL)

    The anti-fertility effect of the aqueous and ethanol extracts of the leaves and roots of Leonotis ocymifolia were studied both in vivo and in vitro. The anti-implantation and anti-fertility activities of the ethanol leaves extract were 37% and 20%, respectively. The body weight recorded for 19 days starting from day 1 of pregnancy ...

  12. Discrimination and Anti-discrimination in Denmark

    DEFF Research Database (Denmark)

    Olsen, Tore Vincents

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

  13. Synthetic drugs with anti-ageing effects.

    Science.gov (United States)

    Kapoor, Vijay K; Dureja, Janhvi; Chadha, Renu

    2009-09-01

    Although ageing is a natural wear and tear phenomenon, it can at least be postponed or prevented by certain approaches. Some chemicals that are present in the diet or in dietary supplements have been documented to have anti-ageing effects. Recently, a number of synthetic drugs used for other therapeutic indications have been shown to have anti-ageing potential.

  14. 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.

  15. 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.

  16. Quantum Zeno and anti-Zeno paradoxes

    Indian Academy of Sciences (India)

    anti-Zeno paradox. Here we discuss the quantum Zeno and anti-Zeno paradoxes which arise due to infinitely frequent measurements of time independent and .... follow a presentation due to Martin [11]. Consider an unstable particle B decaying into particles c + D, ... etc. B c + D,.... (10). Suppose that the total Hamiltonian H ...

  17. Combined antiretroviral and anti- tuberculosis drug resistance ...

    African Journals Online (AJOL)

    these epidemics, many challenges remain.[3] Antiretroviral and anti-TB drug resistance pose considerable threats to the control of these epidemics.[4,5]. The breakdown in HIV/TB control within prisons is another emerging threat.[6,7] We describe one of the first reports of combined antiretroviral and anti-TB drug resistance ...

  18. EAMJ March Anti-diabetic.indd

    African Journals Online (AJOL)

    2009-03-03

    Mar 3, 2009 ... offer only a limited selection of essential oral hypoglycaemics and insulin but at a lower price and across all facilities. Twenty six per cent and 10% of patients in public and private facilities respectively are unable to afford anti-diabetic drugs. The need for intervention to increase affordability of anti-diabetic ...

  19. What's Missing? Anti-Racist Sex Education!

    Science.gov (United States)

    Whitten, Amanda; Sethna, Christabelle

    2014-01-01

    Contemporary sexual health curricula in Canada include information about sexual diversity and queer identities, but what remains missing is any explicit discussion of anti-racist sex education. Although there exists federal and provincial support for multiculturalism and anti-racism in schools, contemporary Canadian sex education omits crucial…

  20. Anti-inflammatory and neuropharmacological activities of ...

    African Journals Online (AJOL)

    Anti-inflammatory and neuropharmacological activities of Caesalpinia pulcherrima leaves. U Bose, V Bala, AK Shill, AA Rahman. Abstract. The crude methanolic extracts of leaves of Caesalpinia pulcherrima were evaluated for its anti-inflammatory and neuropharmacological activities. When given orally to rats at dose of ...

  1. Stabiliteit van drijvende lichamen; anti-slingertanks

    NARCIS (Netherlands)

    Bourgingnon, G.P.

    1980-01-01

    Het dempen van de slingerbewegingen (roll) van een drijvend lichaam door middel van tanks met een vrije vloeistofoppervlakte. In de scheepsbouwkunde is vrij veel bekend over het toepassen van anti-slingertanks. De anti-slingertank, die ook dempt bij een stilliggend schip (in tegenstelling tot

  2. Independence requirements for anti-corruption institutions

    African Journals Online (AJOL)

    The Court's approach and these apparent requirements are compared with current provisions for political 'independence' of anti-corruption agencies in Australia and Indonesia, raising, in particular, an assessment of the arguments for and against (a) the need for an anti-corruption investigative agency to be separate from ...

  3. Anti-Semitism: Background to the Holocaust.

    Science.gov (United States)

    Kleg, Milton

    1995-01-01

    Contends that teaching only about the 1933-1945 period of German persecution of Jews serves a very limited purpose. Argues that the foundations of anti-Semitic beliefs and practices have a long history and should be part of Holocaust education. Describes the origins, development, and key events in anti-Semitism in Europe. (CFR)

  4. Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): new biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Bodnár, Nóra; Szekanecz, Zoltán; Prohászka, Zoltán; Kemény-Beke, Adám; Némethné-Gyurcsik, Zsuzsanna; Gulyás, Katalin; Lakos, Gabriella; Sipka, Sándor; Szántó, Sándor

    2012-01-01

    Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS. Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices. Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3-31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4-13.3 U/mL) (p20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2-1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5-88.5 AU/mL) (p<0.001). Correlation analysis revealed that both anti-MCV positivity (r=0.613; p=0.012) and absolute serum anti-MCV levels (r=0.553; p=0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR (r=0.437; p=0.03). Anti-MCV and anti-hsp65 may be novel biomarkers in AS. Copyright © 2011. Published by Elsevier SAS.

  5. EU Lobbying and Anti-Dumping Policy

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Svendsen, Gert Tinggaard

    2012-01-01

    Lobbying in the EU is difficult to measure. It varies in intensity and modes of expression across different policy areas and EU countries. By looking at a specific EU policy area this paper suggests to measure differences in the lobbying activity across EU countries by the combination...... 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...

  6. Anti-atherosclerotic effects of tomatoes

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2017-06-01

    Full Text Available Tomatoes are rich in lycopene, which causes the red coloring of tomatoes. Several reports have suggested lycopene plays a role in the prevention of cardiovascular diseases. In this study, we systematically reviewed the interventional studies using tomatoes or tomato products to understandtheanti-atherosclerotic effects of the tomatoas a functional food. We found that a significantnumber of interventional studies reportedtheanti-atherosclerotic effects of tomatoes, includinganti-obesity effects, hypotensiveeffects, improvement of lipid/glucose metabolismand endothelial function, anti-oxidative and anti-inflammatory effect, and anti-platelet effect; however, the anti-platelet effect was disagreed uponby some studies. Furthermore, we discoveredcooking methods significantlyaffect anti-atherosclerotic effects of tomatoes.

  7. Transformations in French Anti-Semitism

    Directory of Open Access Journals (Sweden)

    Nonna Mayer

    2007-01-01

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

  8. Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

    Science.gov (United States)

    Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

    2010-09-01

    Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

  9. Association of ribosomal anti-P antibodies with different parameters ...

    African Journals Online (AJOL)

    antibodies with neuropsychiatric lupus manifestations and to find out the relationship of ribosomal anti-P antibodies with other autoimmune parameters of lupus. Ribosomal anti-P antibodies were evaluated in the serum of 41 systemic lupus erythematosus (SLE) patients as well as ANA, dsDNA, anti- Sm, anti-SSA, anti-SSB, ...

  10. Pharmacological Experimental Study Of The Anti-Depressant Effect ...

    African Journals Online (AJOL)

    Pharmacological Experimental Study Of The Anti-Depressant Effect Of Total Saikosaponins. Y Liu, C Cao, H Ding. Abstract. Background: Chai Hu has the hepato-protective, choleretic, anti-tussive, analgesic, anti-inflammatory, anti-viral, hypotensive, hypolipidemic, and anti-tumor pharmacological effects. In this study, the ...

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Nonsteroid anti-inflammatory agents.

    Science.gov (United States)

    Paulus, H E; Whitehouse, M W

    1973-01-01

    Nonsteroidal antiinflammatory agents (NSAID) are reviewed. Aspirin, indomethacin, and salicylate have all been shown to interfere or prevent the synthesis of prostaglandins (PGs), a main tissue inflammatory substance. However, an exception to the correlation of PG-synthetase inhibition with antiinflammatory activity has been noted with certain arylacetic acids. Studies on the role of lysosomes in the inflammation are criticized in this review, mainly because of improper understanding of the role of lysosomes in a physiological system. Since lysosomes are not a specific body, but an activator, attempts to isolate lysosomes to study functions are doomed to failure; i.e., a lysosome has no definition without the rest of its self-regulating system. NSAIDs work in 2 main ways; either via antiaggregation or antiinflammation. This may result in drug interactions between various types of NSAIDs. For example, simultaneous administration of aspirin with indomethacine did not produce an additive effect; rather they produced no effect in the rat paw edema test dissimilar to the action of either drug separately. However, hydrocortisone combined with another NSAID enhanced its antiinflammatory effects. Albumin binding theories of NSAID mechanism of action state that drugs are active only when albumin-bound because it has displaced tryptophane, or urate, or some other normally bound substance. The only way to discover an efficient antiinflammatory agent is to obviate the need for it by discovering the actual mechanism of inflammation, for when specific anti-etiologic therapy is developed, the need for treatment with NSAIDs is irrelevant.

  13. 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.

  14. 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.

  15. Anti-Terrorism Efforts in Indonesia

    OpenAIRE

    Juwana, Hikmahanto

    2014-01-01

    Terrorism is defined generally under the Anti-Terrorism Law as the intentional use of ‘violence or the threat of violence to create a widespread atmosphere of terror or fear in public'. Indonesia is a victim of terrorism, but at the same time, a safe haven for terrorists. The Indonesian government has taken various measures to eradicate terrorism, yet the Anti-Terrorism Law has not been effective in eradicating terrorist acts in Indonesia. Implementation and enforcement of Anti-Terrorism Law ...

  16. Self Retaining Anti-Rotation Key

    Science.gov (United States)

    Dixon, Alan Benjamin Christopher (Inventor)

    2015-01-01

    Anti-rotation keys are typically used in applications where an end of a threaded stud is received in a housing, and where the opposite end of the stud projects from the housing to allow attachment of another component to the housing. Once partially received in the housing, further rotation of the stud is prevented by an anti-rotation key. The disclosed anti-rotation key is self-retaining, in that it prevents itself from "backing out" of the channel due to vibration or thermal expansion of the housing, etc., while also being removable from the channel if desired.

  17. Adaptive H∞ Chaos Anti-synchronization

    International Nuclear Information System (INIS)

    Ahn, Choon Ki

    2010-01-01

    A new adaptive H ∞ anti-synchronization (AHAS) method is proposed for chaotic systems in the presence of unknown parameters and external disturbances. Based on the Lyapunov theory and linear matrix inequality formulation, the AHAS controller with adaptive laws of unknown parameters is derived to not only guarantee adaptive anti-synchronization but also reduce the effect of external disturbances to an H ∞ norm constraint. As an application of the proposed AHAS method, the H ∞ anti-synchronization problem for Genesio–Tesi chaotic systems is investigated. (general)

  18. The prozone effect exerted by the complement-binding anti-Lea on anti-D.

    Science.gov (United States)

    Joshi, Sanmukh R; Parekh, Kamlesh H

    2017-01-01

    Prozone phenomenon is seen with very high-titer antibodies in an immune serum. The prozone effect on anti-D by a low-titer anti-Le a was investigated associated with neonatal jaundice. Standard methods were used in investigations. The child was born at full-term developed mild jaundice. With weak direct antiglobulin test+, her indirect serum bilirubin was progressed to 27.5 mg/dL in 48 h. Anti-D and anti-Le a were detected in the mother. Both these antibodies were detected in the child's serum though the eluate from red blood cells (RBCs) contained only anti-D. Mother's anti-D was masked by anti-Le a if the RBCs possessed both the antigens together. Anti-D was revealed only with D-positive RBCs lacking Le a or if the serum was modified by mixing with Le a+ saliva or was heated at 56°C or fortified with citrate solution. An anti-D showed prozone effect exerted by the complement-fixing anti-Le a in the test.

  19. Anti-inflammatory effects of exercise

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund

    2017-01-01

    . In addition, indirect anti-inflammatory effects of long-term exercise are mediated via improvements in body composition. CONCLUSION: Physical activity represents a natural, strong anti-inflammatory strategy with minor side effects and should be integrated in the management of patients with cardiometabolic......BACKGROUND: Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). AIMS: The aim of this review was to provide the reader with an update of the mechanisms whereby exercise-induced cytokines may impact...... and IL-10 is provoked by exercise and exerts direct anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1ra, thereby limiting IL-1β signalling. Moreover, muscle-derived IL-6 appears to have direct anti-inflammatory effects and serves as a mechanism to improve glucose tolerance...

  20. National Health Care Anti-Fraud Association

    Science.gov (United States)

    ... a Glance Pre-Conference Programs Conference Sessions Registration Hotel & Travel Information Conference Tracks Credit Opportunities Anti-Fraud ... care reform bill, titled the “Better Care Reconciliation Act of 2017.” Read More View Older News Stories ...

  1. Prescription Nonsteroidal Anti-Inflammatory Medicines

    Science.gov (United States)

    ... Inflammatory Medicines Share Print Nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines you can take for pain relief. ... well. Path to improved health How do prescription NSAIDs work? NSAIDs stop a certain kind of enzyme ...

  2. 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....

  3. Marine Organisms with Anti-Diabetes Properties

    Directory of Open Access Journals (Sweden)

    Chiara Lauritano

    2016-12-01

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

  4. [Action mechanisms of anti-obesity drugs].

    Science.gov (United States)

    Nagayama, Daiji; Shirai, Kohji

    2009-02-01

    Principle of the treatment of obesity is diet and exercise therapy. However, it is extremely difficult to maintain the effect in the long term. In recent years, mechanism of appetite center and adaptive thermogenesis is gradually clarified. As a tool of new treatment of obesity, anti-obesity drugs come to attract attention in this way. However, anti-obesity drug is not the all-around procedure that has got thinner easily if we use it. Anti-obesity drug should be used carefully to show the availability after having understood each action mechanism. Other than mazindol approved alone in Japan, we explain it in this chapter about sibutramine and rimonabant those are on the clinical trial now. We will mention an adaptation of a certain anti-obesity drug in the middle of an argument.

  5. In vitro evaluation of cytotoxic, anti-proliferative, anti-oxidant, apoptotic, and anti-microbial activities of Cladonia pocillum.

    Science.gov (United States)

    Ersoz, M; Coskun, Z M; Acikgoz, B; Karalti, I; Cobanoglu, G; Cesal, C

    2017-08-15

    The aim of this study was to investigate the anti-proliferative, apoptotic, cytotoxic, and anti-oxidant effects of extracts from the lichen Cladonia pocillumon human breast cancer cells (MCF-7), and to characterize the anti-microbial features.  MCF-7 cells were treated with methanolic C. pocillum extract for 24h. The cytotoxicity of the extract was tested with MTT. Moreover, its anti-proliferative effects were examined with immunocytochemical method. Apoptosis and biochemical parameters were detected in MCF-7. The methanol and chloroform extracts of the lichen were tested for anti-microbial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans using the disc diffusion method and calculation of minimal inhibitory concentrations. Although BrdU incorporation was not observed in MCF-7 cells treated with methanol extract at a concentration above 0.2 mg/mL, a significant decrease was observed int he percentage of PCNA immunoreactive cells in groups treated with 0.2, 0.4, 06, and 0.8 mg/mL methanol extracts of C.pocillum (49±6.3, 44±5.2, 23±2.5, 0, respectively) compared to that of control (85±4.5). The percentage of apoptotic cells significantly increased in groups treated with 0.2, 0.4, 0.6, and 0.8 mg/mL extracts of the C.pocillum (54±3.5, 76±2.6, 77±1.8, 82±4.2, respectively) compared with that of control group (3.9±1.5).The half-maximal inhibitory concentration of the methanol extract against MCF-7 cells was 0.802 mg/mL .Although the chloroform extract showed more effective anti-microbial activity overall, the methanol extract showed higher anti-fungal activity. Collectively, the results of our study indicate that C.pocillum extracts have strong anti-microbial and apoptotic effects. This lichen therefore shows potential for development as a natural anti-microbial, anti-oxidant, and apoptotic agent.

  6. Possible D(*) anti D(*) and B(*) anti B(*) molecular states in the extended constituent quark models

    International Nuclear Information System (INIS)

    Yang, You-Chang; Tan, Zhi-Yun; Ping, Jialun; Zong, Hong-Shi

    2017-01-01

    The possible neutral D (*) anti D (*) and B (*) anti B (*) molecular states are studied in the framework of the constituent quark models, which is extended by including the s-channel one-gluon exchange. Using different types of quark-quark potentials, we solve the four-body Schroedinger equation by means of the Gaussian expansion method. The bound states of D (*) anti D (*) with J PC = 1 ++ , 2 ++ and B (*) anti B (*) with J PC = 0 ++ , 1 +- , 1 ++ , 2 ++ are obtained. The molecular states D* anti D with J PC = 1 ++ and B* anti B with J PC = 1 +- are good candidates for X(3872) and Z 0 b (10610), respectively. The dependence of the results on the model parameters is also discussed. (orig.)

  7. Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant extracts.

    Science.gov (United States)

    Atta, A H; Alkofahi, A

    1998-03-01

    The anti-nociceptive effect of ethanolic extract of 11 traditionally used Jordanian plants was studied by using the acetic acid-induced writhing and hot-plate test in mice. The anti-inflammatory effect of these plants was determined by xylene-induced ear oedema in mice and cotton pellet granuloma test in rats. Mentha piperita, Cinnamomum zeylanicum, Apium graveolens, Eucalyptus camaldulentis, and Ruta graveolens possess an anti-nociceptive effect against both acetic acid-induced writhing and hot plate-induced thermal stimulation. M. piperita, Jasminum officinale, Commiphora molmol, and Beta vulgaris possess an anti-inflammatory effect against acute (xylene-induced ear oedema) and chronic (cotton-pellet granuloma) inflammation. The anti-nociceptive and anti-inflammatory effects were dose dependent. These data affirm the traditional use of some of these plants for painful and inflammatory conditions.

  8. Cultural diversity and anti-poverty policy.

    Science.gov (United States)

    Lamont, Michèle; Small, Mario Luis

    2010-01-01

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

  9. Anti-ulcer potential of Oxystelma esculentum

    OpenAIRE

    Devang J Pandya; Indermeet Singh Anand

    2011-01-01

    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 ...

  10. DIALEKTIKA RADIKALISME DAN ANTI RADIKALISME DI PESANTREN

    Directory of Open Access Journals (Sweden)

    Thohir Yuli Kusmanto

    2015-06-01

    Upaya menentang segala bentuk radikalisme merupakan bagian dari reaksi anti radikalisme. Semangat anti radikalisme muncul sebagai bagian dari resistensi masyarakat. Radikalisme dan anti radikalisme saling berkaitan secara dialektis. Meski­pun keduanya merupakan sesuatu yang paradoks, namun selalu menyatu. Dialektika radikalisme dan anti radikalisme menarik ketika dilihat dalam kehidupan pesantren. Fenomena radikalisme Islam seringkali dihubungkan dengan masya­ra­kat pesantren di Indonesia. Beberapa kelompok masyarakat memahami radikal­isme tumbuh dari pesantren. Pandangan tersebut didasari oleh banyaknya pelaku radikalisme Islam dalam bentuk kekerasan alumni pesantren. Realitas tersebut bisa jadi benar dalam kasus tertentu, tetapi tidak bisa digeneralisasi. Penelitian ini ber­upaya menggali data pandangan pesantren tentang wacana dan praksis radikalisme dan anti radikalisme serta pola resistensinya. Hasil penelitian menunjukkan bahwa masyarakat pesantren menolak, menentang dan aktif membangun spirit anti radikalisme yang diwujud­kan dalam beberapa pola. Temuan penelitian tersebut merupakan sintesis dari tesis yang selama ini menjadi wacana masyarakat tentang radikalisme dan pesantren.

  11. The Superheavy Elements and Anti-Gravity

    International Nuclear Information System (INIS)

    Anastasovski, Petar K.

    2004-01-01

    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 < 64 and 63 < Z <145) exist that demonstrate these capabilities. The nuclei of the first group of elements have the masses with only the property of gravity. The nuclei of the elements of the second group have the masses with both properties: gravity and anti-gravity in two different ranges of curved space-time around the nuclei.. The hypothetical element with Z = 145 is the unique among all elements whose nucleus has only anti-gravity property. It is proposed that this element be named Hawking, in honour of Stephen W. Hawking

  12. Anti-Inflammatory Iridoids of Botanical Origin

    Science.gov (United States)

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

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

    Directory of Open Access Journals (Sweden)

    Okti Nadia Poetri

    2006-12-01

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

  14. Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain.

    Science.gov (United States)

    Menor Almagro, Raúl; Jurado Roger, Aurora; Rodríguez Gutiérrez, Francisco Javier; Solís Díaz, Rocío; Cardiel, Mario Humberto; Salaberri Maestrojuan, José Javier

    2016-01-01

    Several antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain. We retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La. 322 patients, 91% females, were studied (age 44.3±15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (p: 0.001) and negatively with homogeneous (p: 0.016) and cytoplasmic pattern (p: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (p<0.001) and positively with the cytoplasmic one (p<0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La- (p: 0.002) and alopecia with anti-Ro52-/anti-Ro60+/anti-La- (p: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60-/anti-La- (p: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003), and hypocomplementemia with anti-Ro52-/anti-Ro60+/anti-La- (p: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60-/anti-La- (p: 0.003). Our study found significant relationships between

  15. Study of phytochemical, anti-microbial, anti-oxidant, and anti-cancer properties of Allium wallichii.

    Science.gov (United States)

    Bhandari, Jaya; Muhammad, BushraTaj; Thapa, Pratiksha; Shrestha, Bhupal Govinda

    2017-02-08

    There is growing interest in the use of plants for the treatment and prevention of cancer. Medicinal plants are currently being evaluated as source of promising anticancer agents. In this paper, we have investigated the anticancer potential of plant Allium wallichii, a plant native to Nepal and growing at elevations of 2300-4800 m. This is the first study of its kind for the plant mentioned. The dried plant was extracted in aqueous ethanol. Phytochemical screening, anti-microbial assay, anti-oxidant assay, cytotoxicity assay and the flow-cytometric analysis were done for analyzing different phytochemicals present, anti-microbial activity, anti-oxidant activity and anti-cancer properties of Allium wallichii. We observed the presence of steroids, terpenoids, flavonoids, reducing sugars and glycosides in the plant extract and the plant showed moderate anti-microbial and anti-oxidant activity. The IC 50 values of Allium wallichii in different cancer cell lines are 69.69 μg/ml for Prostate cancer (PC3) cell line, 55.29 μg/ml for Breast Cancer (MCF-7) cell line and 46.51 μg/ml for cervical cancer (HeLa) cell line as compared to Doxorubicin (0.85 μg/ml). The cell viability assay using FACS showed that the IC 50 value of Allium wallichii for Burkitt's lymphoma (B-Lymphoma) cell line was 3.817 ± 1.99 mg/ml. Allium wallichii can be an important candidate to be used as an anticancer agent. Separation of pure compounds with bioassay guided extraction, spectrometric analysis and subsequent cytotoxicity assay of the pure bioactive compounds from Allium wallichii is highly recommended as the crude extract itself showed promising cytotoxicity.

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

    OpenAIRE

    Usman, Adiyyatu Sa?idu; Mustaffa, Rapiaah; Ramli, Noraida; 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...

  17. Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid.

    Science.gov (United States)

    Rogerio, Alexandre P; Fontanari, Caroline; Melo, Mirian C C; Ambrosio, Sérgio R; de Souza, Glória E P; Pereira, Paulo S; França, Suzelei C; da Costa, Fernando B; Albuquerque, Deijanira A; Faccioli, Lúcia H

    2006-09-01

    Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the anti-inflammatory activity of the same L. pacari extract in mice injected intraperitoneally with beta-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by beta-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation.

  18. Preclinical testing of Peruvian anti-bothropic anti-venom against Bothrops andianus snake venom.

    Science.gov (United States)

    Schneider, Francisco S; Starling, Maria C; Duarte, Clara G; Machado de Avila, Ricardo; Kalapothakis, Evanguedes; Silva Suarez, Walter; Tintaya, Benigno; Flores Garrido, Karin; Seraylan Ormachea, Silvia; Yarleque, Armando; Bonilla, César; Chávez-Olórtegui, Carlos

    2012-11-01

    Bothrops andianus is a venomous snake found in the area of Machu Picchu (Peru). Its venom is not included in the antigenic pool used for production of the Peruvian anti-bothropic anti-venom. B. andianus venom can elicit many biological effects such as hemorrhage, hemolysis, proteolytic activity and lethality. The Peruvian anti-bothropic anti-venom displays consistent cross-reactivity with B. andianus venom, by ELISA and Western Blotting and is also effective in neutralizing the venom's toxic activities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Production of light (anti-)nuclei and (anti-)hypernuclei with ALICE at the LHC

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    The measurements in smaller collision systems may also provide an input to cosmological searches for segregated primordial anti-matter and dark matter, since anti-nuclei produced in pp and p--A collisions in interstellar space represent a background source in these measurements. Thanks to its excellent particle identification and tracking capabilities, the ALICE detector allows for the measurement of deuterons, tritons, 3He, 4He and their corresponding anti-nuclei. Moreover, the secondary vertices from the mesonic decays of (anti-)hypernuclei can ...

  20. Synthesis, Anti-Bacterial and Anti-Fungal Evaluation of Pyrazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Ashvin D. Panchal

    2012-01-01

    Full Text Available The Series of N-(5-(Substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-4H-1,2,4-triazol-4-amine compounds were prepared by reaction of 4-amino-1,2,4-Triazole with Acetyl Chloride followed by different aromatic aldehydes and cyclization with hydrazine hydrate. The structures of new compounds were confirmed by IR and 1H-NMR spectral data. Anti-bacterial and Anti-fungal activities were evaluated and compared with the standard drugs, some compounds of the series exhibited promising anti-microbial and anti-fungal activity compared to standard drugs.

  1. 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.

  2. Explicit and implicit effects of anti-marijuana and anti-tobacco TV advertisements.

    Science.gov (United States)

    Czyzewska, Maria; Ginsburg, Harvey J

    2007-01-01

    Effects of anti-tobacco and anti-marijuana TV advertisements on explicit (i.e., semantic differential ratings) and implicit (i.e. Implicit Association Test, IAT) attitudes toward tobacco and marijuana were compared. Two hundred twenty nine, 18- to 19-year-old U.S. college students were randomly assigned to anti-tobacco or anti-marijuana PSA viewing conditions. Participants completed a short survey on attitudes to tobacco and marijuana. Afterwards they watched 15 PSAs embedded in a 15-min science program. At the end, all participants completed IAT for marijuana, IAT for tobacco and the assessment of explicit attitudes. Results of ANCOVA revealed a significant interaction between type of TV PSAs watched and implicit attitudes, F(1,223)=7.12, padvertisements watched (i.e., anti-tobacco or anti-marijuana). However, analogical analysis on explicit measures showed that attitudes to marijuana became less negative among students that watched anti-marijuana ads than the group with anti-tobacco ads, F(1,222)=5.79, p<0.02. The discussion focused on the practical and theoretical implications of the observed dissociation between implicit and explicit attitudes to marijuana after the exposure to anti-marijuana PSAs.

  3. Anti-Ma and anti-Ma2-associated paraneoplastic neurological syndromes.

    Science.gov (United States)

    Ortega Suero, G; Sola-Valls, N; Escudero, D; Saiz, A; Graus, F

    Analyse the clinical profile, associated tumour types, and response to treatment of paraneoplastic neurological syndromes associated with antibodies against Ma proteins. A retrospective study of patients with antibodies against Ma proteins identified in a neuroimmunology laboratory of reference. Of the 32 patients identified, 20 showed reactivity against Ma2 only (anti-Ma2 antibodies), 11 against Ma1 and Ma2 (anti-Ma antibodies), and 1 with reactivity against Ma1 only (anti-Ma1 antibodies). The most common clinical presentations were limbic encephalopathy, diencephalic dysfunction, or brainstem encephalopathy, frequently appearing as a combination of these features. Three patients had isolated cerebellar dysfunction with anti-Ma antibodies, and 2 exhibited peripheral nervous system syndrome with anti-Ma2 antibodies. Testicular tumours were the most common neoplasms (40%) in the anti-Ma2 cases. In the group associated with anti-Ma1 antibodies, the most common were lung tumours (36%), followed by testicular tumours. All idiopathic cases were reactive to Ma2. The clinical outcome was significantly better in the anti-Ma2 group. The patient with anti-Ma1 presented with limbic encephalitis and brainstem dysfunction associated with lymphoepithelioma of the bladder. Specifically determining the different reactivities of anti-Ma protein antibodies in order to differentiate between Ma1 and Ma2 antibodies is important because anti-Ma2-associated paraneoplastic syndromes have a better outcome. Lastly, this study is the first to confirm that there may be cases that react exclusively to antibodies against Ma1. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Bioassay guided isolation and identification of anti-inflammatory and ...

    African Journals Online (AJOL)

    The present study describes the anti-inflammatory, anti-microbial activity and lipophilic profile with acute toxicological studies of Urtica dioica. Successive extraction of the leaves with organic solvents of increasing polarity and their screening for anti-inflammatory and anti-microbial activity was assessed. Hexane extract ...

  5. Australia and France on Fire: An Anti-Colonial Critique

    Science.gov (United States)

    Dei, George Sefa; Kempf, Arlo

    2006-01-01

    Professor George Sefa Dei has written and taught extensively in the fields of anti-colonialism and anti-racism. His latest work on the subject is "Anti-Colonialism and Education: The Politics of Resistance," co-edited with Arlo Kempf for Sense Publishers (2006). Dei and Kempf are also co-authoring a forthcoming volume on anti-colonial…

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

    International Nuclear Information System (INIS)

    Senft, Christian; Polacin, Margareth; Priester, Maike; Seifert, Volker; Kögel, Donat; Weissenberger, Jakob

    2010-01-01

    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

  7. Biological activities (anti-inflammatory and anti-oxidant) of fractions ...

    African Journals Online (AJOL)

    Background: Bryophytes like other lower plants (non-vascular plants) are not traditionally employed for therapeutic purposes. Hence this study evaluated the in vitro anti-oxidant potentials and anti-inflammatory activities of the fractions and methanolic extract of Moss (Philonotis hastata, Duby) with a view to studying its ...

  8. 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

  9. Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...

  10. Recherche et Titrage des Hémolysines Anti-A et Anti-B Chez Les ...

    African Journals Online (AJOL)

    Recherche et Titrage des Hémolysines Anti-A et Anti-B Chez Les Femmes en periode du postpartum immédiat au Centre Hospitalier et Universitaire de Yaoundé. D Fopa, CT Tagny, PM Tebeu, A Ndoumba, D Mbanya ...

  11. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer ...

    Indian Academy of Sciences (India)

    ... as anti-bacterial and anti-fungal agents against various microorganisms. The in vitro cytotoxicity tests of the ligand and its copper complex were carried out in two different human tumour cell lines, HCT-116 and MDA – MB - 231. The cytotoxicity studies showed that the complex exhibited higher activity than cisplatin and ...

  12. Sero-Prevalence of anti-sperm anti-bodies in infertile males in Port ...

    African Journals Online (AJOL)

    Background: Infertility is a serious health challenge which causes distress to the couples especially; in Africa. The cause of infertility is multifactorial. Immunological infertility is said to be one of the major causes of unexplained infertility in men. Anti-sperm anti-bodies can be used as an immunological marker of infertility.

  13. Anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with juvenile idiopathic arthritis

    NARCIS (Netherlands)

    van Rossum, Marion; van Soesbergen, Renée; de Kort, Sandra; ten Cate, Rebecca; Zwinderman, Aeilko H.; de Jong, Ben; Dijkmans, Ben; van Venrooij, Walther J.

    2003-01-01

    Objective. To determine if anti-cyclic citrullinated peptide antibodies (anti-CCP) can be detected in sera of patients with juvenile idiopathic arthritis (JIA) and if they can be used to identify patients with a more destructive course of disease. Methods. One hundred serum samples of 71 patients

  14. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer ...

    Indian Academy of Sciences (India)

    copper complex have been investigated as anti-bacterial and anti-fungal agents against various microorganisms. The in vitro cytotoxicity tests of the ..... integration curves and those obtained from the values of the expected CHN analysis, ... two imino nitrogen atoms to form the equatorial plane, with atoms of the same type in ...

  15. Anti-nociceptive and anti-inflammatory properties of the leaf extracts ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the leaf extracts of Hedranthera barteri in rats and mice. SA Onasanwo, RA Elegbe. Abstract. Hedranthera barteri, HB (Apocynaceae) is a shrub in the closed-forest in some parts of West Africa and used among the natives for inflammatory pain relief. This study was carried ...

  16. Anti-thrombotic and anti-tumor effect of water extract of caulis of ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-thrombosis and anti-tumor effect of the water extract of the caulis of Sargentodoxa cuneata (Oliv.) Rehd. et Wils. (WCSW) in rat and mouse models. Methods: WCSW extract was prepared and the main constituents were determined by high pressure liquid chromatography (HPLC). The acute ...

  17. Anti-Stress and Anti-Amnesic Effects of Coriandrum sativum Linn ...

    African Journals Online (AJOL)

    Purpose: Coriandrum sativum Linn. (Umbelliferae, C. sativum) is cultivated throughout the world for its use as spice and as a folk medicine. This study deals with the anti-stress and anti-amnestic properties of C. sativum extract in rats. Methods: Urinary levels of vanillylmandelic acid (VMA) and ascorbic acid were used to ...

  18. Uptake of Anti rabies vaccine by users of the Anti rabies centre ...

    African Journals Online (AJOL)

    Uptake of Anti rabies vaccine by users of the Anti rabies centre Douala, Cameroon : a descriptive cross sectional study. AA Bita Fouda, G Etapelong Sume, N Essomba, E Nguemne, C Anani, D Mbida, E Ekosso, A Feuhgouo, G Noufack Zambou, J Owona Manga ...

  19. Anti-inflammatory and anti-oxidant activities of Secamone afzelii ...

    African Journals Online (AJOL)

    . This study re-ports the anti-inflammatory and antioxidant properties of S. afzelii. The anti-inflammatory activity was determined by the carrageenan-induced paw oedema method in 7 day old chicks and antioxi-dant property by the 2 ...

  20. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer ...

    Indian Academy of Sciences (India)

    DOI 10.1007/s12039-015-0824-z. Synthesis, structure analysis, anti-bacterial and in vitro anti-cancer activity of new Schiff base and its copper complex derived from sulfamethoxazole. I RAMA∗ and R SELVAMEENA. PG and Research Department of Chemistry, Seethalakshmi Ramaswami College,. Tiruchirappalli 620 002 ...

  1. GC–MS profile, anti-seizure and anti-pyretic activities of palm kernel ...

    African Journals Online (AJOL)

    PURPOSE: Palm kernel nut oil (PKNO) from palm fruit of a rare breed of Elaeis guineensis (virescens), and one of the species belonging to the Elaeis genre of arecaceae family was subjected to Gas chromatography - Mass spectroscopic studies as well as anti-seizure and anti-pyretic studies. It is used in South-Eastern part ...

  2. The anti-inflammatory and anti-nociceptive activities of Patrinia ...

    African Journals Online (AJOL)

    This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX ...

  3. 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.

  4. Anti-icing performance of superhydrophobic surfaces

    Science.gov (United States)

    Farhadi, S.; Farzaneh, M.; Kulinich, S. A.

    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 ˜80 μm) in a wind tunnel at subzero temperature (-10 °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.

  5. Anti-damping effect of radiation reaction

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  6. Anti-NMDA Receptor Encephalitis and Vaccination.

    Science.gov (United States)

    Wang, Hsiuying

    2017-01-18

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

  7. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem

    Science.gov (United States)

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Objective: Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). Materials and Methods: The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. Results: OHS extract inhibited acetic acid-induced writhing (pdiseases. PMID:28884086

  8. Anti-nociceptive and anti-inflammatory effects of the methanolic extract ofOpuntia humifusastem.

    Science.gov (United States)

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Opuntia humifusa ( O. humifusa ) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. OHS extract inhibited acetic acid-induced writhing (pdiseases.

  9. Experimental comparison of EMC effect in the anti νn and anti νp interactions in neon nucleus

    International Nuclear Information System (INIS)

    Asratyan, A.E.; Efremenko, V.I.; Fedotov, A.V.

    1985-01-01

    In the framework of the method used to separate the antiν and antiνp interactions in the neon nucleus, a strong distinction of the quantity Rsub(Ne)(x)=(dσsup(antiνn)/dx)/(dσsup(antiνp)/dx) measured in this anti νNe experiment from the analogous quantity Rsub(D)(x) obtained earlier in a deuterium experimentis found. This difference can be attributed to the difference between the magnitudes of the EMC effect in the anti νn and anti νp scattering

  10. Observations on fluxes near anti-branes

    Energy Technology Data Exchange (ETDEWEB)

    Cohen-Maldonado, Diego [Institute of Physics, University of Amsterdam, Science Park,Postbus 94485, Amsterdam, 1090 GL The (Netherlands); Diaz, Juan; Riet, Thomas Van [Instituut voor Theoretische Fysica, K.University Leuven,Celestijnenlaan 200D, Leuven, B-3001 (Belgium); Vercnocke, Bert [Institute of Physics, University of Amsterdam, Science Park,Postbus 94485, Amsterdam, 1090 GL The (Netherlands)

    2016-01-20

    We revisit necessary conditions for gluing local (anti-)D3 throats into flux throats with opposite charge. These consistency conditions typically reveal singularities in the 3-form fluxes whose meaning is being debated. In this note we prove, under well-motivated assumptions, that unphysical singularities can potentially be avoided when the anti-branes polarise into spherical NS5 branes, with a specific radius. If a consistent solution can then indeed be found, our analysis seems to suggests a rather large correction to the radius of the polarization sphere compared to the probe result. We furthermore comment on the gluing conditions at finite temperature and point out that one specific assumption of a recent no-go theorem can be broken if anti-branes are indeed to polarise into spherical NS5 branes at zero temperature.

  11. Anti-integrin therapy for multiple sclerosis.

    Science.gov (United States)

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

    2012-01-01

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

  12. 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.

  13. Mitosis as an anti-cancer target.

    Science.gov (United States)

    Janssen, A; Medema, R H

    2011-06-23

    Most of the current drugs used to treat cancer can be classified as anti-proliferative drugs. These drugs perturb the proliferative cycle of tumor cells at diverse stages of the cell cycle. Examples of such drugs are DNA-damaging agents and inhibitors of cyclin-dependent kinases that arrest cell cycle progression at different stages of interphase. Another class of anti-proliferative drugs is the so-called anti-mitotic drugs, which selectively perturb progression through mitosis. Mitosis is the shortest and final stage in the cell cycle and has evolved to accurately divide the duplicated genome over the two daughter cells. This review deals with the different strategies that are currently considered to perturb mitotic progression in the treatment of cancer.

  14. Performative Pedagogy in Teaching Anti-Racism

    Directory of Open Access Journals (Sweden)

    Nena Močnik

    2015-06-01

    Full Text Available The paper deals with the issue of effective anti-racism teaching in everyday contexts, where the traditional forms of racism are replaced by more sophisticated, subtle practices of exlusion, hatred and violence. Historical connotations of terms such as racism, xenophobia, homophobia, etc. specifically characterize certain groups of people and somehow further deepen divisions between the hegemonic majority and the oppressed minority; therefore, several indicators of inefficience in teaching anti-racism have appeared, particularly in applying theories into practices. Teaching anti-racism is presented through new attitudes towards performative pedagogy, for a long time understood in the context of the teacher as the actor who engage his/her students as spectators through variety of acting techniques and performative practies. Along with the theoretical and applied development of the field, more and more the performative pedagogy is recognized as a critical teaching approach, based on artistic expression, improvisation, continuous dialogue, and the body as an ideologically inscribed product.

  15. Anti-inflammatory mechanisms of sepsis.

    Science.gov (United States)

    Shubin, Nicholas J; Monaghan, Sean F; Ayala, Alfred

    2011-01-01

    Over the past two decades, it has become well accepted that sepsis exhibits two, oftentimes concomitant, inflammatory stages; a pro-inflammatory phase, referred to as the systemic inflammatory response syndrome (SIRS), and an anti-inflammatory phase, called the compensatory anti-inflammatory response syndrome (CARS). Considering that therapeutic interventions designed to attenuate the pro-inflammatory septic response have generally failed, much recent research has gone into understanding how and why septic patients display immunosuppressive characteristics, what the significance of septic immunosuppression may be and if there exists any therapeutic targets within the CARS. Herein, we describe the potential mechanisms of the immunosuppressive/CARS phase of sepsis by discussing what anti-inflammatory agents, receptors and cell populations are currently believed to contribute to CARS. Copyright © 2011 S. Karger AG, Basel.

  16. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    Specific inhibition of the cytokine, tumor necrosis factor-α (TNF), has revolutionized the treatment of patients with several autoimmune diseases, and genetically engineered anti-TNF antibody constructs now constitute a heavy medicinal expenditure in many countries. Unfortunately, up to 30...... of protein drugs. The use of therapeutic strategies based on anti-TNF drug levels and ADA rather than dose-escalation has also proven to be cost-effective, as this allows individualized patient-tailored strategies rather than the current universal approach to loss of response. The objective of the present...... article - and the accompanying article - is to discuss the reasons for recommending assessments of circulating drug and ADA levels in patients treated with anti-TNF biopharmaceuticals and to detail some of the methodological issues that obscure cost-effective and safer therapies....

  17. What is an anti-aging treatment?

    Science.gov (United States)

    Gems, David

    2014-10-01

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

  18. PENDIDIKAN ANTI KORUPSI; UPAYA PREVENTIF MEMBERANTAS KORUPSI

    Directory of Open Access Journals (Sweden)

    Mohammad Kosim Mohammad Kosim

    2012-03-01

    Full Text Available AbstractThis writing will describe corruption that up to now still become big problem for a number of countries, especially for the poor and developing ones. The negative effect of corruption is  both from the material side and immaterial. Therefore, with any reasons, corruption cannot be accepted and must be eliminated. The elimination of corruption must be done repressively and preventively. One of the preventive ways proposed in this writing is trough education anti corruption, especially trough family and school.Kata-kata kuncikorupsi, pendidikan anti korupsi

  19. 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.

  20. In defense of anti-matter

    International Nuclear Information System (INIS)

    Rogers, S.; Thompson, W.B.

    1980-01-01

    There appears to be a prejudice in the astronomical world against an obvious high-energy source - the mutual annihilation of matter and anti-matter. In favor of this prejudice is the lack of any convincing evidence of the presence of naturally occurring anti-matter. Only recently have cosmic-ray antiprotons been detected (cf. Golden et al., 1979), and then in numbers consistent with secondary production in flight, while annihilation X-rays have also been detected, but again in circumstances where they might well be attributed to secondary effects of some other high-energy process. (orig.)

  1. Anti-anaphylactic effect of Euphorbia hirta.

    Science.gov (United States)

    Youssouf, M S; Kaiser, P; Tahir, M; Singh, G D; Singh, S; Sharma, V K; Satti, N K; Haque, S E; Johri, R K

    2007-12-01

    The Euphorbia hirta ethanolic extract (EH A001) was found to possess a prominent anti-anaphylactic activity. A preventive effect of EH-A001 given by oral route at dose from 100 to 1000 mg/kg was observed against compound 48/80-induced systemic anaphylaxis. At the same range of dose, EH-A001 inhibited passive cutaneous anaphylaxis (PCA) in rat and active paw anaphylaxis in mice. A suppressive effect of EH-A001 was observed on the release of TNF-alpha and IL-6 from anti-DNP-HSA activated rat peritoneal mast cells.

  2. Anti-nuclear movement and art

    International Nuclear Information System (INIS)

    Go, Seung Woo; Yun, Beom Mo

    1989-08-01

    This book goes into in detail of nuclear weapon and independent unification in the Korean peninsula. So it describes how to build of peace of circumstances both inside and outside the Korean peninsula, how to deal with nuclear crisis of the Korean peninsula and to overcome nuclear crisis. Especially, this book deals with art which is used to resist nuclear and war including art activity for unity, anti-nuclear war, Kollwitz's etching as a connecting tool with public and a painting about atom bomb pictured by Maruky in Japan who worked for anti-nuclear war.

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

    Directory of Open Access Journals (Sweden)

    Piacente S

    2006-03-01

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

  4. 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.

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

    Science.gov (United States)

    Virella, G; Hyman, B

    1991-01-01

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

  6. The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

    Science.gov (United States)

    Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

    2015-04-01

    Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

  7. The effects of areca catechu L extract on anti-inflammation and anti-melanogenesis.

    Science.gov (United States)

    Lee, K K; Choi, J D

    1999-08-01

    Ethanolic extract (CC-516) from Areca catechu L was prepared and its various biological activities were evaluated, CC-516 showed potent anti-oxidative, free radical scavenging, and anti-hyaluronidase activity. Anti-oxidative effect of CC-516 (IC _ 50: 45.4 mug/ml) was lower than butylated hydroxytoluene (IC _ 50: 5mug ml), but similar to tocopherol and higher than ascorbic acid. Especially, CC-516 exhibited relatively high free radical scavenging activity (IC _ 50: 10.2 mug/ml) compared to control. CC-516 inhibited effectively hyaluronidase activity (IC _ 50: 416 mug/ml), showed inhibition in vivo on delayed hypersensitivity as well as croton-oil induced ear edema in mice when it was topically applied. These results strongly suggest that CC-516 may reduce immunoregulatory/inflammatory skin trouble. Also, from the results, we have elucidated that CC-516 showed anti-allergic and anti-cytotoxicity activity. The whitening effect of CC-516 shown by the inhibition of mushroom tyrosinase activity with IC _ 50 of 0.48 mg/ml and of melanin synthesis in B16 melanoma cells. This study indicates that CC-516 is effective on anti-inflammatory/anti-melanogenesis, and can be used as a new agent for cosmetics.

  8. 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.

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

    International Nuclear Information System (INIS)

    Chekanov, S.; Derrick, M.; Magill, S.

    2007-05-01

    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 0.3 T /M<0.7. The particle rates have been extracted and interpreted in terms of the coalescence model. The (anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements. (orig.)

  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. Anti-inflammatory activity of Taraxacum officinale.

    Science.gov (United States)

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

    2008-01-04

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

  12. Potency of Nicotiana tabacum as anti - microfouling

    Science.gov (United States)

    Aunurohim, Nurilma, Dian Ahmada; Kuswytasari, Nengah Dwianita

    2017-06-01

    In general, the attachment and growth of organisms on the surface of the object or material immersed in the sea are called Biofouling. Biofouling microscopic called microfouling, where it acts as a precursor of the next engaging organisms that are generally larger in size (called macrofouling). In recent time, biofouling control over the use of chemicals in antifouling paints. Usage tributyltin polishing copolymer paints (TBT - SPC paint) containing TBT has adverse effects on non-target marine organisms. This study uses tobacco dust as an anti-microfouling, which is the waste generated during the process of tobacco leaves. Five of bacterial isolates have been founded at Surabaya coastal in a preliminary test with iron plates. Then those isolates tested to detect and visualized of biofilm. The activity of anti-bacteria had been done and the result is known that more high of tobacco extract given, a diameter of zone inhibit high too. The extract of tobacco dust can be applied most effectively to be anti-microfouling is a concentration of 40%, isolates 3 and 4 are a type of bacteria that is most inhibited growth. So, in this result, Nicotiana tabacum is potential as an anti-microfouling.

  13. Tomato leaves methanol extract possesses anti- inflammatory ...

    African Journals Online (AJOL)

    GREGORY

    2011-12-16

    Dec 16, 2011 ... demonstrated, the anti-inflammatory effect of tomato leaves and its associated molecular mechanisms have not yet been fully investigated. ... This mechanism is an immunological response following bacterial infection and is ... inflammatory drugs (NSAIDs) that are mainly used in the treatment of pain and ...

  14. 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, meliorism,…

  15. Anti-inflammatory drugs and psychosis

    NARCIS (Netherlands)

    Laan, W.

    2008-01-01

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

  16. Anti-Depressants, Suicide, and Drug Regulation

    Science.gov (United States)

    Ludwig, Jens; Marcotte, Dave E.

    2005-01-01

    Policymakers are increasingly concerned that a relatively new class of anti-depressant drugs, selective serotonin re-uptake inhibitors (SSRI), may increase the risk of suicide for at least some patients, particularly children. Prior randomized trials are not informative on this question because of small sample sizes and other limitations. Using…

  17. Anti-angiogenic treatment of gastrointestinal malignancies.

    Science.gov (United States)

    Salmon, J Stuart; Lockhart, A Craig; Berlin, Jordan

    2005-01-01

    The scientific rationale to block angiogenesis as a treatment strategy for human cancer has been developed over the last 30 years, but is only now entering the clinical arena. Preclinical studies have demonstrated the importance of the vascular endothelial growth factor (VEGF) pathways in both physiologic and pathologic angiogenesis, and have led to the development of approaches to block its role in tumor angiogenesis. Bevacizumab is an antibody to VEGF and has been shown to prolong survival when given with chemotherapy in the treatment of metastatic colorectal cancer (CRC). Although this is the first anti-angiogenic treatment to be approved for the treatment of human epithelial malignancy, a number of other approaches currently are in development. Soluble chimeric receptors to sequester serum VEGF and monoclonal antibodies against VEGF receptors have both shown considerable promise in the laboratory and are being brought into clinical investigation. A number of small-molecule tyrosine kinase inhibitors that have activity against VEGF receptors also are in clinical trials. Although these novel treatments are being pioneered in CRC, anti-angiogenic approaches also are being tested in the treatment of other gastrointestinal malignancies. Anti-VEGF therapy has shown promise in such traditionally resistant tumors as pancreatic cancer and hepatocellular carcinoma. This review will examine the preclinical foundation and then focus on the clinical studies of anti-VEGF therapy in gastrointestinal cancers.

  18. The Anti-Trash Costume Bash

    Science.gov (United States)

    Stokrocki, Mary

    2010-01-01

    To educate one's students about recycling garbage, art teachers can plan an "anti-trash costume bash" to promote public awareness of the ugly, unhealthy, and costly effects of litter. Such an event was brainstormed by the Maricopa Association of Governments (MAG), a regional agency made up of the valley communities in Arizona working to…

  19. Reconciling Anti-essentialism and Quantitative Methodology

    DEFF Research Database (Denmark)

    Jensen, Mathias Fjællegaard

    2017-01-01

    Quantitative methodology has a contested role in feminist scholarship which remains almost exclusively qualitative. Considering Irigaray’s notion of mimicry, Spivak’s strategic essentialism, and Butler’s contingent foundations, the essentialising implications of quantitative methodology may prove...... the potential to reconcile anti-essentialism and quantitative methodology, and thus, to make peace in the quantitative/qualitative Paradigm Wars....

  20. PHARMACOGNOSTIC AND ANTI-DIARRHOEAL STUDIES OF ...

    African Journals Online (AJOL)

    PHARMACOGNOSTIC AND ANTI-DIARRHOEAL STUDIES OF LEAVES OF FICUS THONNINGII. ... In all the doses, there was an initial increase in purgation by the 2nd h of the test, but this was followed by constipation. The results supported the co-occurrence of astringent and purgative compounds in the crude drug.

  1. Platinum compounds with anti-tumour activity

    NARCIS (Netherlands)

    Plooy, A.C.M.; Lohman, P.H.M.

    1980-01-01

    Ten platinum (Pt) coordination complexes with different ligands, comprising both Pt(II) and Pt(IV) complexes of which the cis-compounds all possessed at least some anti-tumour activity and the trans-compounds were inactive, were tested as to their effect on cell survival and the induction and repair

  2. 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...

  3. Anti-vaccination movements and their interpretations

    NARCIS (Netherlands)

    Blume, S.

    2006-01-01

    Over the last two or three decades, growing numbers of parents in the industrialized world are choosing not to have their children vaccinated. In trying to explain why this is occurring, public health commentators refer to the activities of an anti-vaccination ‘movement’. In the light of three

  4. 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.

  5. 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…

  6. Λ(anti Λ) beams at FNAL

    International Nuclear Information System (INIS)

    Overseth, O.

    1977-01-01

    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

  7. Quantum Zeno and anti-Zeno paradoxes

    Indian Academy of Sciences (India)

    Abstract. 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.

  8. Chemical Characterization, Anti inflammatory and Analgesic ...

    African Journals Online (AJOL)

    Chemical Characterization, Anti inflammatory and Analgesic Properties of Jatropha Multifida Root Bark. ... Phytochemical investigations reveal the presence of alkaloids, tannins, glycosides, saponins and flavonoids. The extract at a dose of 400 mg/kg significantly (P < 0.01) reduced paw thickness in rat compared to control.

  9. Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Fischer, M.; Behr, T.; Gruenwald, F.; Knapp, W.H.; Truemper, L.; Schilling, C. von

    2004-01-01

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkin-lymphomas 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 the treatment has to be carried out technically. Here, quality control and documentation of labelling are of greatest 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 (haematology-oncology) who propose, in general, radioimmunotherapy under consideration of the development of the disease. (orig.)

  10. [Guideline for radioimmunotherapy of rituximab relapsed or refractory CD20(+) follicular B-cell non-Hodgkin's lymphoma].

    Science.gov (United States)

    Fischer, M; Behr, T; Grünwald, F; Knapp, W H; Trümper, L; von Schilling, C

    2004-10-01

    This guideline is a prerequisite for the quality management in the treatment of non-Hodgkin-lymphomas 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 the treatment has to be carried out technically. Here, quality control and documentation of labelling are of greatest 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 (haematology-oncology) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

  11. CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells

    DEFF Research Database (Denmark)

    Peipp, M.; Wesch, D.; Oberg, H. H.

    2017-01-01

    Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explor...

  12. Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Živković Valentina

    2014-01-01

    Full Text Available Introduction. In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE and their use in everyday clinical practice. Objective. Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. Methods. The study enrolled 85 patients aged 45.3±9.7 years on the average, with SLE of average duration 10.37±7.99 years, hospitalized at the Institute „Niška Banja“ during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI. In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany. Results. Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p<0.01. SLE patients with SLEDAI ≥11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p<0.01 and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05, as well as a higher mean level of anti-nucleosome antibodies (107.79±83.46 U/ml vs. 57.81±63.15 U/ml; p<0.05, compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01, anti-nucleosome (r=0.443; p<0.001, and anti-C1q antibodies (r=0.382; p<0.001. Only anti-C1q antibodies demonstrated correlation with proteinuria (r=0.445; p<0.001. Conclusion. Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis

  13. Anti-inflammatory responses of resveratrol.

    Science.gov (United States)

    Das, Samarjit; Das, Dipak K

    2007-09-01

    Resveratrol (trans-3,4',5-trihydroxystilbene), a natural polyphenolic, non-flavonoid antioxidant, is a phytoalexin found in many plants including grapes, nuts and berries. Recent studies have documented that resveratrol has various health benefits, such as cardiovascular and cancer preventive properties. However, the experimental basis for such health benefit is not fully understood. One of the possible mechanisms for its protective activities is by down regulation of the inflammatory responses. That includes the inhibition of synthesis and release of pro-inflammatory mediators, modifications of eicosanoid synthesis, inhibition of some activated immune cells, or inhibiting the enzymes, such as cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2), which are responsible for the synthesis of pro-inflammatory mediators through the inhibitory effect of resveratrol on transcription factors like nuclear factor kappaB (NFkappaB) or activator protein-1 (AP-1). Being a phenolic compound, resveratrol certainly possesses a low bioavailability and most importantly, a rapid clearance from the plasma. Recent growing interest in varying protective nature of resveratrol may clinically also hold a respectable position as a better alternative for anti-inflammatory drugs. The purpose of this review is to provide evidence that resveratrol exhibits potent anti-inflammatory activity and also to explain the underling mechanism for both resveratrol- induced cardioprotective and anti-inflammatory properties. While it is true that the cardioprotective properties of resveratrol are likely attributable, at least in part, to its anti-inflammatory properties, the mechanisms discussed address foremost mechanisms for the anti-inflammatory activity which, in turn, is responsible for cardioprotection.

  14. Future of anti-addiction vaccines.

    Science.gov (United States)

    Kosten, Thomas R

    2005-01-01

    The medical rational for using anti-drug antibodies in the serum as a treatment is to reduce drug levels in the brain and to bind drug before it enters the brain. Drugs of abuse are small molecules that can readily cross the blood brain barrier, while antibodies are larger molecules that cannot get into the brain. Thus, any drug that is bound to antibody also cannot cross the blood brain barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body to makes its own antibodies, but the small size of abused drugs prevents them from stimulating an immune response. Thus, individuals do not ordinarily produce antibodies to abused drugs, and vaccines to stimulate antibodies are made by chemically linking these abused drugs to toxins such as cholera toxin. Alternatively, passive immunotherapy uses monoclonal antibodies that are generated in a laboratory and then administered via intravenous injection. Antibodies can be used to treat drug overdose; to reduce drug use relapse; or to protect certain at risk populations who have not yet become drug dependent. The advantages of anti-addiction vaccines are that antibodies target the drug, not the drug's sites of action in the brain and antibody binding inactivates the drug. These vaccines can complement behavioral and other medical therapies with minimal side effects and are not addictive like some chemical agonists. Technology advances in manufacturing and delivery systems will improve future anti-addiction vaccines, but social acceptance of anti-addiction vaccines will depend on substance abuse program staff and the families of substance abusers, who have some values that oppose medical solutions to addictive diseases and view addictions as moral problems.

  15. Brief History of Anti-Doping.

    Science.gov (United States)

    Ljungqvist, Arne

    2017-01-01

    The fight against doping in sport as we know it today commenced by the creation of the International Olympic Committee (IOC) Medical Commission in 1961 following the death of a Danish cyclist during the Rome Olympic Games the year before. After a slow start, the fight got under way as from the early 1970s under the leadership of the IOC and of the International Association of Athletics Federations. Despite a lack of understanding and weak support even from the sports community, a series of measures were taken during the 1970s and 1980s which still form cornerstones of today's anti-doping strategy. In addition to information and education campaigns, the most important examples are the introduction of procedural rules for doping controls, the establishment and follow-up of a list of prohibited substances and methods, the accreditation of doping control laboratories, the introduction of in- and out-of-competition testing, rules for therapeutic use exemption, and the introduction of blood sampling. During the 1990s, the anti-doping fight gained increasing support both inside and outside the sport community. In order to harmonize the wide variety of rules that had developed both in sport organizations and at the domestic level and to promote anti-doping activities, the World Anti-Doping Agency (WADA) was jointly created by the Olympic movement and the public authorities in 1999. WADA is today carrying on the fight supported by the universally accepted WADA Code and an International Anti-Doping Convention under UNESCO. © 2017 S. Karger AG, Basel.

  16. Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model.

    Science.gov (United States)

    Ozkars, M Y; Keskin, O; Tokur, M; Ulasli, M; Gogebakan, B; Ciralik, H; Kucukosmanoglu, E; Demirel, C; Oztuzcu, S; Kahraman, H

    2017-11-27

    Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. The results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  17. 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.

  18. [Wegener's granulomatosis with anti-neutrophil cytoplasmic antibodies against anti-cathepsin G antigen].

    Science.gov (United States)

    Ocaña Pérez, E; Peña Casas, A M; del Campo Muñoz, T; Avila Casas, A; Luque Barona, R

    2013-12-01

    Wegener's granulomatosis belongs to the group of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies characterized by granulomatous inflammation and necrotising vasculitis in various organs with particular involvement of the upper and lower respiratory tracts and kidneys. Wegener's granulomatosis is a rare disorder in childhood and early diagnosis of this disease is critical to the long-term prognosis of the disease. The presence of positive cytoplasmic antineutrophil cytoplasmic antibody staining or a high titre of proteinase 3 antibodies were added as new criteria of vasculitis in childhood. This article presents a case of Wegener's granulomatosis, with the presence of anti-neutrophil cytoplasm antibodies with cytoplasmic pattern with absence of anti-proteinase 3 antibodies and presence of high levels of anti-cathepsin G antibodies, rarely described in Wegener's granulomatosis. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  19. Anti-tumour, anti-mutagenic and chemomodulatory potential of Chlorophytum borivilianum.

    Science.gov (United States)

    Kumar, Manish; Meena, Priyadarshi; Verma, Shekhar; Kumar, Madhu; Kumar, Ashok

    2010-01-01

    In the present investigation anti-tumour, anti-mutagenic and chemomodulatory potential of Chlorophytum borivilianum were evaluated. Chlorophytum borivilianum root extract had no toxic effect up to a dose of 800 mg/kg body weight/day. Significant increase (pChlorophytum borivilianum root extract when compared with the control value. Skin papillomagenesis studies demonstrated a significant (pChlorophytum borivilianum root extract at a dose level of 800 mg/kg body weight/day orally in double distilled water at pre, peri and post initiation stages of carcinogenesis. A significant reduction in the frequency of chromosomal aberration and micronuclei was observed in the treated animals as compared to carcinogen controls. The present investigation suggests that Chlorophytum borivilianum has anti-tumour, anti-mutagenic and chemomodulatory effects.

  20. Sericins exhibit ROS-scavenging, anti-tyrosinase, anti-elastase, and in vitro immunomodulatory activities.

    Science.gov (United States)

    Chlapanidas, Theodora; Faragò, Silvio; Lucconi, Giulia; Perteghella, Sara; Galuzzi, Marta; Mantelli, Melissa; Avanzini, Maria Antonietta; Tosca, Marta Cecilia; Marazzi, Mario; Vigo, Daniele; Torre, Maria Luisa; Faustini, Massimo

    2013-07-01

    Some biological properties of Bombyx mori sericins from twenty strains were investigated, fourteen fed with artificial diet, two with fresh mulberry leaves and four with both diets. Sericin exhibited ROS-scavenging, anti-tyrosinase and anti-elastase properties, the strain significantly influenced these properties, while diet only influenced the anti-tyrosinase activity. Sericins were clustered into 5 groups and one sericin from each group was further studied: sericins showed anti-proliferative activity on in vitro stimulated peripheral blood mononuclear cells; some strains decreased in vitro secretion of IFNγ, while no effects were observed on TNFα and IL10 release. Therefore, a mixture of sericins extracted from the most promising strains may be useful for dermatological and cosmetic use. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    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, anti-microbial 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. PMID:19701969

  2. Antibacterial, anti-swarming and anti-biofilm formation activities of Chamaemelum nobile against Pseudomonas aeruginosa

    OpenAIRE

    Hossein Kazemian; Sobhan Ghafourian; Hamid Heidari; Pouya Amiri; Jalil Kardan Yamchi; Aref Shavalipour; Hamidreza Houri; Abbas Maleki; Nourkhoda Sadeghifard

    2015-01-01

    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, fru...

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

    OpenAIRE

    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 urgently required to deal with these biofilm-mediated infections. Plants are a rich source of new molecules with pharmacological properties for the development of new drugs. Indonesia is one of the cou...

  4. 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.

  5. 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.

  6. 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.

  7. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    .... The necessity of anti-optimization approach is first demonstrated, then the anti-optimization techniques are applied to static, dynamic and buckling problems, thus covering the broadest possible set of applications...

  8. [Opportunities and defiance of therapeutic anti-tumoral vaccination].

    Science.gov (United States)

    Coulie, P

    2007-01-01

    Therapeutic anti-cancer vaccines containing tumor-specific antigens recognized by T lymphocytes are thought to stimulate high numbers of anti-vaccine cytolytic T lymphocytes (CTL) which then can lyse the tumor cells. To understand why these vaccines are followed by tumor regressions in only 10% of the patients, we analysed the tumor-specific immune responses of these patients. Contrary to our expectations, the anti-vaccine CTL responses were of very low level. However, regressing tumors were massively infiltrated by anti-tumor T cells of other specificities, including new anti-tumor CTL clonotypes that emerged following vaccination. We now believe that the role of the anti-vaccine CTL is to activate or restimulate large numbers of other anti-tumor CTL. Their ability to initiate this response is probably more important than their number. These results have important consequences for the improvement of the clinical efficacy of anti-cancer vaccines.

  9. 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.

  10. fJ(2220) and hadronic anti Bs0 decays

    International Nuclear Information System (INIS)

    Hsiao, Y.K.; Geng, C.Q.

    2015-01-01

    We study the hadronic anti B s 0 decays based on the existence of the resonant state f J (2220). In particular,we are able to explain the unexpected large experimental result of B(anti B s 0 → J/ψp anti p) = (3.0 -1.1 +1.2 ± 0.52 ± 0.03) x 10 -6 measured recently by the LHCb collaboration due to the resonant contribution in anti B s 0 → J/ψf J (2220) with f J (2220) → p anti p, while it is estimated to be at most of order 10 -9 in terms of the OZI rule without the resonance. In addition, we find that B(anti B s 0 → D *0 (f J →)p anti p) = (4.70 ± 2.89) x 10 -7 , B(anti B s 0 → J/ψ(f J →)ππ) = (15.6 ± 15.2) x 10 -6 , and B(anti B s 0 → D *0 (f J →)ππ) = (24.5 ± 24.4) x 10 -7 , while B(anti B s 0 → J/ψ(f J →)K anti K) < 1.6 x 10 -5 and B(anti B s 0 → D *0 (f J →)K anti K) < 2.5 x 10 -6 . Moreover, we predict that the decay branching ratios of anti B s 0 → (J/ψ, D *0 )Λ anti Λ are (2.68 ± 1.23) x 10 -7 and (2.25 ± 0.80) x 10 -6 . Some of the predicted anti B s 0 decays are accessible to the experiments at the LHCb. (orig.)

  11. Current status on narrow N anti N states

    International Nuclear Information System (INIS)

    Chung, S.U.

    1979-09-01

    An attempt is made to summarize the experimental status of narrow B anti B states as of mid-1979. In particular, concentration is placed on the current experimental situations and prospects regarding three serious contenders for the so-called baryonium states. Theoretical concepts of baryoniums, narrow N anti N states known as S(1935), anti pp(2020), and anti pp(2204), and some forthcoming results, and problems of the above three resonances are discussed. 31 references

  12. Anti-synchronization Between Coupled Networks with Two Active Forms

    International Nuclear Information System (INIS)

    Wu Yongqing; Sun Weigang; Li Shanshan

    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. (general)

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

    Science.gov (United States)

    Thitimuta, Surached; Pithayanukul, Pimolpan; Nithitanakool, Saruth; Bavovada, Rapepol; Leanpolchareanchai, Jiraporn; Saparpakorn, Patchreenart

    2017-03-04

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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Surached Thitimuta

    2017-03-01

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

  16. Natural products and anti-inflammatory activity.

    Science.gov (United States)

    Yuan, Gaofeng; Wahlqvist, Mark L; He, Guoqing; Yang, Min; Li, Duo

    2006-01-01

    The aim of this review paper was to summarise some commonly available natural products and their anti-inflammatory activity. We have collected data from MEDLINE, Current Contents and scientific journals, which included 92 publications. There are numerous natural products detailed in this literature; however we have summarized a few of the most commonly available and potent ones. In this paper, the natural products with anti-inflammatory activity including curcumin, parthenolide, cucurbitacins, 1,8-cineole, pseudopterosins, lyprinol, bromelain, flavonoids, saponins, marine sponge natural products and Boswellia serrata gum resin were reviewed. Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Further studies are being conducted to investigate the mechanism of action, metabolism, safety and long term side effect of these natural products, as well as interactions between these natural products with food and drug components.

  17. [The anti-asylum movement in Brazil].

    Science.gov (United States)

    Lüchmann, Lígia Helena Hahn; Rodrigues, Jefferson

    2007-01-01

    This study reviews the history of the national anti-asylum struggle in Brazil. It analyzes some of the movement's difficulties, achievements and challenges. The theory of social movements is used here as an important analytical tool to understand this collective action, to the degree in which theory allows an appraisal of this type of social action rooted in its many configurations, evidencing the complexity of the contemporary world. The anti-asylum movement is composed of many stakeholders whose struggles and conflicts have been developed through different social-political-institutional dimensions. It encompasses at different moments and to different degrees, a movement which articulates solidarity and conflict relations and social denunciations in an attempt to transform relations and conceptions that are discriminatory and which are intended to control the "insane" and "insanity" in our country.

  18. Anti-Infectious Agents against MRSA

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    2012-12-01

    Full Text Available Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652 targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.

  19. Prospects for Anti-Biofilm Pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Philip S. Stewart

    2015-08-01

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

  20. [Anti-ageing therapies in Alzheimer's disease].

    Science.gov (United States)

    Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael

    Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Prospects for Anti-Biofilm Pharmaceuticals

    Science.gov (United States)

    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 drugs that block microbial adhesion or interfere with intercellular communication, developing chemistries to disperse biofilms, and combining agents with different mechanisms of action. Though the need is great, the pathway to commercialization of new drugs is steep. One possible streamlined approach to navigating the regulatory approval process is to repurpose old drugs, a strategy that a few groups have shown can yield agents with anti-biofilm properties. PMID:26343685

  2. 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 has...

  3. Anti-platelet aggregation of mixtures of betulinic oleanolic and ...

    African Journals Online (AJOL)

    Original Research Article. Anti-platelet aggregation of mixtures of betulinic oleanolic ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals. (DOAJ), African Journal Online, Bioline ... antiseptic, aphrodisiac, anti-emetic, anti- inflammatory and carminative properties [5,6].

  4. 48 CFR 352.203-70 - Anti-lobbying.

    Science.gov (United States)

    2010-10-01

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

  5. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    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

  6. Anti-Ulcer Effect of Risperidone in Rats | Onwuchekwa | African ...

    African Journals Online (AJOL)

    Risperidone is a second-generation atypical antipsychotic drug currently used for the management of psychosis in schizophrenia, delusional psychosis and psychotic depression an action ascribed to its being a dopamine antagonist possessing anti-serotonergic, anti-adrenergic and anti-histaminergic properties. However ...

  7. The Phytochemical Constituents, Analgesic and Anti-inflammatory ...

    African Journals Online (AJOL)

    This effect was comparable to the observed effect with Piroxicam (0.5mg/kg) which was used as a standard. The effect was also dose- dependent. Furthermore, Jatropha ... This also supports its use traditionally as an anti-snake bite, rheumatism and anti- cancer or anti-tumor agent. Further study is on the way to find out the ...

  8. Earlier and later anti-psychologism in linguistics

    NARCIS (Netherlands)

    Elffers, E.

    2014-01-01

    Psychologism has been a mainstream view in linguistics throughout many centuries. Serious and prominent anti-psychologism flourished in the first half of the 20th century, mainly in European structuralism. As a minority view, mostly dubbed ‘anti-mentalism’, anti-psychologism resurfaced in the 1970s

  9. Anti-Oxidant potentials of Yaji spices | Okpalaugo | International ...

    African Journals Online (AJOL)

    ... anti-parasitic, anti-helmintic and anti-oxidant potentials. Common amongst these spices are ginger, clove, red pepper and black pepper, which in combination, constitutes the main spices in Yaji –a complex Nigerian Suya-meat sauce that also contain groundnut cake flour, Ajinomoto (monosodium glutamate) and salt.

  10. Anti-counterfeiting features of artistic screening

    OpenAIRE

    Ostromoukhov, V.; Rudaz, N.; Amidror, I.; Emmel, P.; Hersch, R. D.

    1996-01-01

    Although Artistic Screening has been designed mainly for performing the creation of graphic designs of high artistic quality, it also incorporates several important anti-counterfeiting features. For example, bank notes or other valuable printed matters produced with Artistic Screening may incorporate both full size and microscopic letters of varying shape into the image halftoning process. In this contribution, we show that frequency modulated screen dots exhibit a strongly position-dependent...

  11. Anti inflammatory effects of statin in COPD

    OpenAIRE

    Nasef Abdelsalam Rezk; Ahmad Elewa

    2013-01-01

    Introduction: Statins are now becoming recognized as powerful antiinflammatory agents that exert beneficial effects beyond low-density lipoprotein cholesterol reduction [1]. COPD patients receiving statins obtain a benefit from these therapeutic agents. Clearly, the best medical evidence for the association of statins with improved outcomes for COPD patients [2]. We aimed in this study to assess anti inflammatory effects of statin in COPD patients. Patients and methods: We studied 28...

  12. Anti-Integrin Therapy for Multiple Sclerosis

    OpenAIRE

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

    2012-01-01

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

  13. 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.

  14. Anti-mafia initiatives in Germany

    Directory of Open Access Journals (Sweden)

    Giulia Norberti

    2017-11-01

    Full Text Available Le ricerche degli ultimi anni suggeriscono che l’espansione delle mafie italiane in territorio tedesco stia avvenendo nell’indifferenza generale. Stato e autorità locali, così come società civile e media, non stanno dedicando sufficiente attenzione alla tematica. L’obiettivo di questo articolo è invece di identificare e mappare le numerose organizzazioni e i tanti eventi che sono stati organizzati negli ultimi anni, nel tentativo di analizzare la dimensione e le dinamiche del movimento antimafia in Germania. I risultati raccolti suggeriscono che, contrariamente al previsto, esistono molte persone e gruppi attivi in questo settore, anche se non sempre raggiungono un visibile impatto. Parole chiave: Germania, movimento antimafia, Mafia? Nein, Danke! e.V., educazione antimafia, giornalismo   Current research suggests that the expansion of Italian mafia groups in Germany is taking place almost completely unnoticed, as neither the state and regional institutions, nor civil society and the media are giving sufficient attention to the issue. The purpose of the paper is to identify and map the numerous organizations and events that have taken place in recent years, in an attempt to analyse the dimension and the dynamics of the anti-mafia movement in Germany. Taken together, these results suggest that there are many individuals and groups that are doing something in the anti-mafia field, even if they are not always reaching an adequate level of efficacy. Keywords: Germany, Anti-mafia movement, Mafia? Nein, Danke! e.V., Anti-mafia education, Journalism

  15. Immunogenicity of Anti-TNF-α Biotherapies

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2015-01-01

    Immunogenicity of biopharmaceuticals is complex and influenced by both structural and pharmacological factors, and by patient-related conditions such as disease being treated, previous and concomitant therapies, and individual immune responsiveness. Essential for tailored therapeutic strategies...... 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...

  16. Proteomics of anti-cancer drugs

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

    2009-01-01

    Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

  17. 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.

  18. Anti-atherosclerotic effects of konjac

    OpenAIRE

    Hidekatsu Yanai; Hiroki Adachi; Hisayuki Katsuyama; Hidetaka Hamasaki; Akahito Sako

    2015-01-01

    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 ...

  19. Gravity controlled anti-reverse rotation device

    Science.gov (United States)

    Dickinson, Robert J.; Wetherill, Todd M.

    1983-01-01

    A gravity assisted anti-reverse rotation device for preventing reverse rotation of pumps and the like. A horizontally mounted pawl is disposed to mesh with a fixed ratchet preventing reverse rotation when the pawl is advanced into intercourse with the ratchet by a vertically mounted lever having a lumped mass. Gravitation action on the lumped mass urges the pawl into mesh with the ratchet, while centrifugal force on the lumped mass during forward, allowed rotation retracts the pawl away from the ratchet.

  20. 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...

  1. Association between anti-thyroid peroxidase and anti-cytokeratin 18 autoantibodies and bronchial asthma in women

    Directory of Open Access Journals (Sweden)

    Hala A. Mohammad

    2016-01-01

    Conclusion: Positive anti-TPO autoantibodies and anti-CK18 autoantibodies in asthmatic patients and their higher level in the non-allergic asthma group may strengthen the presence of a hidden autoimmune phenomenon in non-allergic asthma.

  2. Anti- Sporothrix spp. activity of medicinal plants

    Directory of Open Access Journals (Sweden)

    Stefanie Bressan Waller

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

  3. 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.

  4. News exposure predicts anti-Muslim prejudice.

    Directory of Open Access Journals (Sweden)

    John H Shaver

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

  5. News exposure predicts anti-Muslim prejudice.

    Science.gov (United States)

    Shaver, John H; Sibley, Chris G; Osborne, Danny; Bulbulia, Joseph

    2017-01-01

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

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

    Science.gov (United States)

    Mohan, C G; Deepak, M; Viswanatha, G L; Savinay, G; Hanumantharaju, V; Rajendra, C E; Halemani, Praveen D

    2013-04-13

    To evaluate the anti-oxidant and anti-inflammatory activity of leaf extracts and fractions of Mangifera indica in in vitro conditions. 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. In in vitro DPPH radical scavenging activity, the MEMI, EMEMI and BMEMI have offered significant antioxidant activity with IC(50) values of 13.37, 3.55 and 14.19 μg/mL respectively. Gallic acid, a reference standard showed significant antioxidant activity with IC(50) 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 IC(50) 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 IC(50) 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. These findings suggest that the MEMI and EMEMI possess potent anti-oxidant and anti-inflammatory activities in in vitro conditions. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  7. More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy

    Directory of Open Access Journals (Sweden)

    Shang-Der Chen

    2017-03-01

    Full Text Available In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2 as well as erythropoietin (EPO-dependent stimulation of sonic hedgehog (SHH. We further revealed that BDNF may bring the expression of sulfiredoxin, an ATP-dependent antioxidant enzyme, to offset mitochondrial inhibition in cortical neurons. Recently, we provided insights into another novel anti-oxidative mechanism of BDNF, which involves the augmentation of sestrin2 expression to endow neuronal resistance against oxidative stress induced by 3-NP; BDNF induction of sestrin2 entails the activation of a pathway involving nitric oxide (NO, cyclic guanosine monophosphate (cGMP-dependent protein kinase (PKG, and nuclear factor-κB (NF-κB. Apart from anti-apoptosis and anti-oxidation, we demonstrated in our most recent study that BDNF may activate the mammalian target of rapamycin (mTOR with resultant activation of transcription factor c-Jun, thereby stimulating the expression of p62/sequestosome-1 to suppress heightened autophagy as a result of 3-NP exposure. Together, our results provide in-depth insight into multi-faceted protective mechanisms of BDNF against mitochondrial dysfunction commonly associated with the pathogenesis of many chronic neurodegenerative disorders. Delineation of the protective signaling pathways elicited by BDNF would endow a rationale to develop novel therapeutic regimens to halt or prevent the progression of neurodegeneration.

  8. Limonoids and their anti-proliferative and anti-aromatase properties in human breast cancer cells.

    Science.gov (United States)

    Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimanagouda S

    2013-02-01

    Lemons are a widely used citrus crop and have shown several potential health benefits. In the present study, the mechanism and effectiveness of the anti-cancer and anti-aromatase properties of limonoids were investigated for the first time. Defatted lemon (Citrus lemon L. Burm) seed powder was extracted with ethyl acetate (EtOAc) and methanol (MeOH) for 16 h each, successively. These extracts were fractionated using 1D (silica) and 2D (ion exchange and SP-70 columns) column chromatography to obtain nine limonoids. The compounds were identified by TLC, HPLC, and LC-MS techniques. A panel of 9 purified limonoids, including limonin, nomilin, obacunone, limonexic acid (LNA), isolimonexic acid (ILNA), nomilinic acid glucoside (NAG), deacetyl nomilinic acid glucoside (DNAG), limonin glucoside (LG) and obacunone glucoside (OG) as well as 4 modified compounds such as limonin methoxime (LM), limonin oxime (LO), defuran limonin (DL), and defuran nomilin (DN), were screened for their cytotoxicity on estrogen receptor (ER)-positive (MCF-7) or ER-negative (MDA-MB-231) human breast cancer cells. We further tested the mechanism of the anti-proliferative activity of limonoids using an in vitro aromatase enzyme assay and western blot with anti-caspase-7. Among the tested limonoids, 11 limonoids exhibited cytotoxicity on MCF-7 whereas 8 limonoids showed cytotoxicity against the MDA-MB-231 cell lines. Although most of the limonoids showed anti-aromatase activity, the inhibition of proliferation was not related to the anti-aromatase activity. On the other hand, the anti-proliferative activity was significantly correlated with caspase-7 activation by limonoids. Our findings indicated that the citrus limonoids may have potential for the prevention of estrogen-responsive breast cancer (MCF-7) via caspase-7 dependent pathways.

  9. Synthesis and biological evaluation of 2-aminoimidazole/carbamate hybrid anti-biofilm and anti-microbial agents.

    Science.gov (United States)

    Rogers, Steven A; Lindsey, Erick A; Whitehead, Daniel C; Mullikin, Trey; Melander, Christian

    2011-02-15

    The successful marriage of structural features from our 2-aminoimidazole and menthyl carbamate classes of anti-biofilm agents has resulted in the development of a novel hybrid scaffold of biofilm modulators. The compounds were evaluated against a panel of four bacterial strains for anti-biofilm and anti-microbial activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

    Directory of Open Access Journals (Sweden)

    Mayada Ali Abdalla

    2018-01-01

    Conclusion: Anti-NCS antibodies could play a role in the pathogenesis of SLE and is related to disease activity. Its association with anti-dsDNA antibodies and its presence in those with negative anti-ds DNA may aid in the diagnosis of SLE.

  11. Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

    Science.gov (United States)

    Jansen, Anke; Mandić, Ana D; Bennek, Eveline; Frehn, Lisa; Verdier, Julien; Tebrügge, Irene; Lutz, Holger; Streetz, Konrad; Trautwein, Christian; Sellge, Gernot

    2016-12-01

    Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

  12. B0 → D0 anti D0K0, B+ → D0 anti D0K+, and the scalar D anti D bound state

    International Nuclear Information System (INIS)

    Dai, L.R.; Xie, Ju-Jun; Oset, E.

    2016-01-01

    We study the B 0 decay to D 0 anti D 0 K 0 based on the chiral unitary approach, which generates the X(3720) resonance, and we make predictions for the D 0 anti D 0 invariant mass distribution. From the shape of the distribution, the existence of the resonance below threshold could be induced. We also predict the rate of production of the X(3720) resonance to the D 0 anti D 0 mass distribution with no free parameters. (orig.)

  13. 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.

  14. Anti-amyloidogenic effect of thiacremonone through anti-inflamation in vitro and in vivo models.

    Science.gov (United States)

    Lin, Gui Hua; Lee, Young-Jung; Choi, Dong-Young; Han, Sang Bae; Jung, Jae Kyung; Hwang, Bang Yeon; Moon, Dong Cheul; Kim, Youngsoo; Lee, Myung Koo; Oh, Ki-Wan; Jeong, Heon Sang; Leem, Jae Yoon; Shin, Hwa Kyoung; Lee, Jung Hwa; Hong, Jin Tae

    2012-01-01

    Neuroinflammation is implicated for amyloidogenesis. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects. To investigate thiacremonone's potential effect on anti-neuroinflammation and anti-amyloidogenesis, 4 week old ICR mice were given different doses of thiacremonone (1, 3, and 10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of lipopolysaccharide (LPS) (250 μg/kg/day) at last 7 days of treatment. Our data show thiacremonone decreased LPS-induced memory impairment, glial activation, pro-inflammatory mediators' expression, and amyloidogenesis. In an in vitro study, we obtained similar results, with thiacremonone (1, 2, and 5 μg/ml) effectively decreased LPS (1 μg/ml)-induced glial activation and inflammatory mediators generation which are implicated in amyloidogenesis. Our data also demonstrated that thiacremonone inhibited LPS-induced amyloidogenesis in cultured astrocytes and microglial BV-2 cells. NF-κB, a critical transcriptional factor regulating not only inflammation but also amyloid-β generation, was inhibited by thiacremonone via blocking of phosphorylation of IκBα in mice brain as well as cultured astrocytes and microglial BV-2 cells. These results indicated that the anti-inflammatory compound, thiacremonone, inhibited neuroinflammation and amyloidogenesis through inhibition of NF-κB activity, and thus could be applied for intervention of inflammation-related neurodegenerative disease including Alzheimer's disease.

  15. In vivo anti-nociceptive and anti-inflammatory activities of Lippia alba

    Directory of Open Access Journals (Sweden)

    Sagnik Haldar

    2012-10-01

    Full Text Available Objective: To evaluate antinociceptive and anti-inflammatory activities of Lippia alba (Mill. N.E. Brown (Verbenaceae leaves. Methods: Soxhlet extraction method was used to obtain extracts using petroleum ether extracts (PELA; chloroform extracts (CELA; ethanol extracts (EELA and aqueous extract (AELA. Antinociceptive activity was assessed on rats by tail flick latency using tail immersion method and anti-inflammatory activity was estimated by carrageenan induced paw edema method. PELA, CELA and AELA at a dose of 500 mg /kg.b.wt. and EELA at a dose of 460 mg /kg.b.wt were administered orally. Result: Competing to control AELA was found to have a higher range of anti-nociceptive activity and showing maximum (79.66% response at 60 min, where as CELA and EELA were found to have a maximum range of anti-inflammatory activity and CELA exhibit maximum (19.5% response at 240 min. Conclusion: The results suggest that the extracts of Lippia alba possess ant-inociceptive and anti-inflammatory activities, and its help to authenticates the use of the plant in the traditional treatment of ailments associated with pain and inflammation.

  16. 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.

  17. Anti-oxidant, hypoglycemic and anti-hyperglycemic properties of Syzygium calophyllifolium

    Directory of Open Access Journals (Sweden)

    Rahul Chandran

    2015-08-01

    Full Text Available The article discusses anti-oxidant oral glucose tolerance and anti-hyperglycemic potentials of Syzygium calophyllifolium. Extracts from successive solvent extraction were tested for the total phenolic, tannin, flavonoid content and free radical scavenging property using DPPH, ABTS+, phosphomolyb-denum, FRAP, superoxide and metal chelating assays. Ethyl acetate extract of bark responded well against DPPH (IC50 4.13, ABTS+ (36832.29 µM TE/ g extract,phosphomolybdenum (100.4 g AAE/100g extract, superoxide and metal ion radicals. The methanol extract of bark was also found as an effective radical scavenger. The leaf methanol extract also showed significant anti-oxidant ability. The bark methanol extract could potentially reduce the blood glucose level in glucose loaded and diabetic rats. The immense anti-oxidant potential of S. calophyllifolium leaf and bark extracts could be taken as a good source of natural anti-oxidant supplement in food to defend oxidative stress related disorders like diabetes.

  18. 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...

  19. [Advances in study on anti-tumor mechanism of andrographolide].

    Science.gov (United States)

    Qi, Cui-Ling; Wang, Li-Jing; Zhou, Xin-Lei

    2007-10-01

    In recent years, more and more attention was payed to the study of andrographolide. Andrographolide has the extensive pharmacological actions, such as anti-tumor, dephlogisticate and antibiosis and anti-virus. It was dected that andrographolide had the action of anti-tumor in gastric cancer, liver cancer, lung cancer and breast cancer. The anti-tumor mechanism of andrographolide was versatile, for instance, andrographolide can induce the apoptosis of cancer cell, inhibit the cell cycle, and increase the antitumor activity of lymphocyte. The following review was about the recent progress of study on the anti-tumor mechanism of andrographolide.

  20. Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents

    OpenAIRE

    Lamie, P.F.; Philoppes, J.N.; El-Gendy, A.O.; Rárová, L. (Lucie); Grúz, J. (Jiří)

    2015-01-01

    Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic activity. (ZE)-2-[4-(1-Hydrazono-ethyl) phenyl]isoindoline-1,3-dione (12) showed remarkable anti-microbial activity. Its activity against Bacillus subtilis was 133%, 106% and 88.8% wh...

  1. An intelligent anti-jamming network system of data link

    Science.gov (United States)

    Fan, Xiangrui; Lin, Jingyong; Liu, Jiarun; Zhou, Chunmei

    2017-10-01

    Data link is the key information system for the cooperation of weapons, single physical layer anti-jamming technology has been unable to meet its requirements. High dynamic precision-guided weapon nodes like missiles, anti-jamming design of data link system need to have stronger pertinence and effectiveness: the best anti-jamming communication mode can be selected intelligently in combat environment, in real time, guarantee the continuity of communication. We discuss an anti-jamming intelligent networking technology of data link based on interference awareness, put forward a model of intelligent anti-jamming system, and introduces the cognitive node protocol stack model and intelligent anti-jamming method, in order to improve the data chain of intelligent anti-jamming ability.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

    2007-05-15

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

  3. 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......The small Ca-binding protein, S100A4, has a well-established metastasis-promoting activity. Moreover, its expression is tightly correlated with poor prognosis in patients with numerous types of cancer. Mechanistically, the extracellular S100A4 drives metastasis by affecting the tumor...... of T cells to the site of the primary tumor. In vitro studies demonstrated that this antibody efficiently reduced the invasion of T cells in a fibroblast monolayer. Moreover, it was capable of suppressing the invasive growth of human and mouse fibroblasts. We presume therefore that the antibody exerts...

  4. Anti-tumor activity of non-steroidal anti-inflammatory drugs: Cyclooxygenase-independent targets

    Science.gov (United States)

    Liggett, Jason L.; Zhang, Xiaobo; Eling, Thomas E.; Baek, Seung Joon

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively for analgesic and antipyretic treatments. In addition, NSAIDs reduce the risk and mortality to several cancers. Their mechanisms in anti-tumorigenesis are not fully understood, but both cyclooxygenase (COX)-dependent and -independent pathways play a role. We and others have been interested in elucidating molecular targets of NSAID-induced apoptosis. In this review, we summarize updated literature regarding cellular and molecular targets modulated by NSAIDs. Among those NSAIDs, sulindac sulfide and tolfenamic acid are emphasized in this review because these two drugs have been well investigated for their anti-tumorigenic activity in many different types of cancer. PMID:24486220

  5. Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis.

    Science.gov (United States)

    Challener, Gregory J; Jones, Jonathan D; Pelzek, Adam J; Hamilton, B JoNell; Boire, Gilles; de Brum-Fernandes, Artur José; Masetto, Ariel; Carrier, Nathalie; Ménard, Henri A; Silverman, Gregg J; Rigby, William F C

    2016-02-01

    The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts. Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis. We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa- in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa- were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase. In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.

  6. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    Science.gov (United States)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J H M; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with FcγRIII, with less Fc-fucosylation strengthening the interaction. Anti-D IgG1 Fc-glycosylation patterns in 93 plasma samples from 28 male and 28 female Dutch HIDs and RhIG were analyzed with mass spectrometry. The Fc-glycosylation profiles of HIDs were evaluated with regard to their immunization history. HID sera demonstrated clearly lowered anti-D Fc-fucosylation compared to normal IgG fucosylation (93%); this was more pronounced for female than for male HIDs (47% vs. 65%, p = 0.001). RhIG preparations from seven manufacturers varied greatly in the level of Fc-fucosylation (56%-91%). The level of fucosylation slightly increased upon repeated immunization, although it remained fairly constant over time. The RhIG from the different manufacturers all demonstrated increased Fc-galactosylation (64%-82%) compared to total IgG (38%-51%). RhIG preparations vary in Fc-fucosylation and all demonstrate increased galactosylation. Despite not knowing the exact working mechanism, immunoprophylaxis could perhaps be optimized by selection of donors whose anti-D have low amounts of Fc-fucose, to increase the clearance activity of anti-D preparations, as well as high amounts of galactosylation, for anti-inflammatory effects. Implementing a biologic assay in the standardization of RhIG preparations might be considered. © 2014 AABB.

  7. Experimental evaluation of analgesic, anti-inflammatory and anti-platelet potential of Dashamoola

    Directory of Open Access Journals (Sweden)

    Reshma R Parekar

    2015-01-01

    Full Text Available Background: Dashamoola, in the form of arishta and kwath, is a commonly used classical Ayurvedic multi-ingredient formulation for management of pain, arthritis and inflammatory disorders. Objective: To study analgesic, anti-inflammatory and anti-platelet activity of Dashamoola and its combination with aspirin. Materials and Methods: Wistar albino rats (180-200 g and Swiss albino mice (20-25 g of either sex were divided randomly into five groups: Distilled water, aspirin (500mg/kg in rats; 722.2 mg/kg in mice, Dashamoolarishta (1.8 mL/kg in rats; 2.5 mL/kg in mice and Dashamoolarishta with aspirin. Anti-inflammatory activity was measured by change in paw volume in carrageenan-induced inflammation, protein content in model of peritonitis and granuloma weight in cotton pellet granuloma. Analgesic effect was evaluated by counting number of writhes in writhing model. Maximum platelet aggregation and percentage inhibition of ADP and collagen-induced platelet aggregation were estimated in vitro. Statistical analysis was done using one way ANOVA (post hoc Tukey′s test and P < 0.05 was considered significant. Results: Dashamoolarishta and its combination with aspirin showed significantly (P < 0.01 less number of writhes. It showed significant (P < 0.001 anti-inflammatory activity by paw edema reduction in rats, decrease in proteins in peritoneal fluid (P < 0.001 and decrease in granuloma weight (P < 0.05 as compared to respective vehicle control groups. Dashamoola kwath alone and in combination with aspirin inhibited maximum platelet aggregation and percent inhibition of platelets as compared to vehicle (P < 0.001. Conclusion: Dashamoola formulation alone and its combination with aspirin showed comparable anti-inflammatory, analgesic and anti-platelet effects to aspirin.

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

    DEFF Research Database (Denmark)

    Nielsen, Jørgen Ulff-Møller; Hansen, Jørgen Drud

    be a surprise, as the same total level of protection may be obtained by using the anti-dumping procedure exclusively. When calculating the two duties in the EU the outcome depends on whether the subsidies are export subsidies or domestic subsidies and this may also cause surprise. This paper addresses......’ competition completely and because a parallel investigation may increase the probability of a successful outcome for the petitioners. In contrast, we find that the different assumptions about the effect of export subsidies and domestic production subsidies on the dumping margin in the EU dual anti...

  9. NLO QCD corrections to top anti-top bottom anti-bottom production at the LHC

    CERN Document Server

    Bredenstein, Axel; Dittmaier, Stefan; Pozzorini, Stefano

    2010-01-01

    The next-to-leading order (NLO) QCD corrections to top anti-top bottom anti-bottom (tTbB) production at the LHC reveal that the scale choice adopted in previous lowest-order simulations underestimates the tTbB cross section by a factor two. We discuss a new dynamical scale that stabilizes the perturbative predictions and describe the impact of the corrections on the shape of distributions. We also account for the techniques employed to compute the six-particle one-loop amplitudes with high CPU efficiency.

  10. 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.

  11. Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.

    Science.gov (United States)

    Bukhari, Ishfaq A; Gilani, Anwar H; Meo, Sultan Ayoub; Saeed, Anjum

    2016-02-25

    Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa. Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests. The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml. The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

  12. Anti-S. typhi Vi IgG levels in children with and without typhoid vaccinations

    Directory of Open Access Journals (Sweden)

    Sriandayani Sriandayani

    2014-10-01

    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 anrioody 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-secrional study at Tuminring District, 11anado 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 0.12; 950/£1 0.17 to 0.44; P0.0381. The proportion of children with protective antiNi antioody level was higher in the vaccinated group (23.7% than in the control group  (10.5%, howevet; 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 ooth groups. Also, the proportion of children with protective antibody levels is not significantly

  13. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

    Science.gov (United States)

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-01-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

  14. Anti-inflammatory Nanomedicine for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Shunsuke Katsuki

    2017-12-01

    Full Text Available Coronary artery disease, in the development of which inflammation mediated by innate immune cells plays a critical role, is one of the leading causes of death worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins are a widely used lipid-lowering drug that has lipid-independent vasculoprotective effects, such as improvement of endothelial dysfunction, antioxidant properties, and inhibitory effects on inflammation. Despite recent advances in lipid-lowering therapy, clinical trials of statins suggest that anti-inflammatory therapy beyond lipid-lowering therapy is indispensible to further reduce cardiovascular events. One possible therapeutic option to the residual risk is to directly intervene in the inflammatory process by utilizing a nanotechnology-based drug delivery system (nano-DDS. Various nano-sized materials are currently developed as DDS, including micelles, liposomes, polymeric nanoparticles, dendrimers, carbon nanotubes, and metallic nanoparticles. The application of nano-DDS to coronary artery disease is a feasible strategy since the inflammatory milieu enhances incorporation of nano-sized materials into mononuclear phagocytic system and permeability of target lesions, which confers nano-DDS on “passive-targeting” property. Recently, we have developed a polymeric nanoparticle-incorporating statin to maximize its anti-inflammatory property. This statin nanoparticle has been tested in various disease models, including plaque destabilization and rupture, myocardial ischemia-reperfusion injury, and ventricular remodeling after acute myocardial infarction, and its clinical application is in progress. In this review, we present current development of DDS and future perspective on the application of anti-inflammatory nanomedicine to treat life-threatening cardiovascular diseases.

  15. Disease specificity of anti-tryptophan hydroxylase-1 and anti-AIE-75 autoantibodies in APECED and IPEX syndrome.

    Science.gov (United States)

    Chida, Natsuko; Kobayashi, Ichiro; Takezaki, Shunichiro; Ueki, Masahiro; Yamazaki, Yasuhiro; Garelli, Silvia; Scarpa, Riccardo; Horikawa, Reiko; Yamada, Masafumi; Betterle, Corrado; Notarangelo, Luigi D; Yawaka, Yasutaka; Ariga, Tadashi

    2015-01-01

    Autoantibodies to autoimmune enteropathy-related 75 kDa antigen (AIE-75) and villin are disease markers of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome which is characterized by a peripheral tolerance defect. On the other hand, anti-tryptophan hydroxylase-1 (TPH-1) antibodies are detected in autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED), a central tolerance defect, especially when complicated with gastrointestinal dysfunction. However, to date, anti-AIE-75 and anti-villin antibodies or anti-TPH-1 antibodies have not been tested in APECED or IPEX syndrome, respectively. In the present study, we confirmed the disease specificity of both anti-AIE-75 and anti-TPH-1, although anti-villin antibodies were detected in some patients with APECED. Our observation suggests that immunotolerance to AIE-75 depends on the peripheral mechanism, whereas the tolerance to TPH-1 depends on the central mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 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.

  17. Anti-inflammatory activity of Lippia dulcis.

    Science.gov (United States)

    Pérez, S; Meckes, M; Pérez, C; Susunaga, A; Zavala, M A

    2005-10-31

    Lippia dulcis hexane and ethanol extracts were tested for its anti-inflammatory activity in several animal models. Hexane extract showed to be inactive, but the ethanol extract at doses of 400 mg/kg produced significant inhibition of carrageenan-induced paw oedema and reduced the weight of cotton pellet-induced granuloma, moreover, the topical application of 0.5 mg/ear of this extract inhibited the edema induced with TPA by 49.13%, an effect which is of less intensity than that produced by indomethacine at the same dose.

  18. Mass in anti-de Sitter spaces

    International Nuclear Information System (INIS)

    Liu, James T.; Sabra, W.A.

    2005-01-01

    The boundary stress tensor approach has proven extremely useful in defining mass and angular momentum in asymptotically anti-de Sitter spaces with CFT duals. An integral part of this method is the use of boundary counterterms to regulate the gravitational action and stress tensor. In the presence of matter, however, ambiguities may arise that are related to the addition of possible finite counterterms. We demonstrate this explicitly for R-charged black holes in AdS 5 , where introduction of a finite counterterm proportional to φ 2 is necessary to properly reproduce the expected mass/charge relation for the black holes

  19. 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...

  20. 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

  1. Anti-Ageing Cultures, Biopolitics and Globalisation

    Directory of Open Access Journals (Sweden)

    Brett Neilson

    2011-11-01

    Full Text Available In March 2004, the author attended the Inaugural International Conference on Longevity at the Sydney Exhibition and Convention Centre in Darling Harbour. As a cultural researcher interested in the interactions between demographic shifts, capitalist globalisation and changing forms of political power, the prospect of a direct encounter with the debates and practices surrounding the burgeoning field of anti-ageing medicine promised a means to observe the complex cultural dynamics of population ageing at play. This article explores the discord the atuhor witnessed; a quarrel that, despite the march of technological advance, attests the ongoing conflict in the nexus where politics meets life.

  2. p anti p collider physics: summary talk

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1985-06-01

    Progress is very briefly summarized in these areas: Drell-Yan production of W and Z; inclusive spectra of jets; angular distribution of two jet final states; Dalitz plot analysis of three jet final states; interior structure of jets; minijets; issues and relevent data in soft-collision physics; structure of the pomeron; W, Z, and electroweak theory; heavy quark physics; extinct exotica; extant exotica, including monojets, the top quark, and possibly anomalous same-sign isolated dimuons. Future directions are anticipated for the Sp anti pS, Tevatron I, instrumentation and detectors, group theory, and the physics at SSC energies. 39 refs., 18 figs

  3. Superfield approach to anti de Sitter supersymmetry

    International Nuclear Information System (INIS)

    Ivanov, E.A.

    1979-01-01

    A self-contained superfield approach to global supersymmetry in anti de Sitter space (OSp(1.4)) is developed. General transformation laws for OSp(1.4)-superfields are established, and all basic elements of the OSp(1.4)-covariant formalism in the real basis, such as covariant superfield derivatives, invariant integration measure over the superspace OSp(1.4)/O(1.3), etc., are explicitly given. The reducibility questions are analyzed and realizations of OSp(1.4) in the left- and right-handed chiral superspaces are found

  4. Human Rights and Cohen's Anti-Statism

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2014-01-01

    , 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...... in distributive justice that it commits us to an implausible anti-statist view of human rights?......G. A. Cohen's critique of standard liberal interpretations of the difference principle has been very influential. According to Cohen, justice is not realized simply because the state's tax policies and other distributive tools maximize the position of the worst off. Rather - possibly in addition to...

  5. Novel anti-inflammatory agents in COPD

    DEFF Research Database (Denmark)

    Loukides, Stelios; Bartziokas, Konstantinos; Vestbo, Jørgen

    2013-01-01

    Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase...... on these strategies exist at the moment. A third potential approach involves novel agents whose mechanism of action is closely related to COPD mechanisms and pathophysiology. Such novel treatments are of great interest since they may treat both COPD and co-morbidities. Several novel agents are currently under...

  6. RAY TRACING RENDER MENGGUNAKAN FRAGMENT ANTI ALIASING

    Directory of Open Access Journals (Sweden)

    Febriliyan Samopa

    2008-07-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Rendering is generating surface and three-dimensional effects on an object displayed on a monitor screen. Ray tracing as a rendering method that traces ray for each image pixel has a drawback, that is, aliasing (jaggies effect. There are some methods for executing anti aliasing. One of those methods is OGSS (Ordered Grid Super Sampling. OGSS is able to perform aliasing well. However, this method requires more computation time since sampling of all pixels in the image will be increased. Fragment Anti Aliasing (FAA is a new alternative method that can cope with the drawback. FAA will check the image when performing rendering to a scene. Jaggies effect is only happened at curve and gradient object. Therefore, only this part of object that will experience sampling magnification. After this sampling magnification and the pixel values are computed, then downsample is performed to retrieve the original pixel values. Experimental results show that the software can implement ray tracing well in order to form images, and it can implement FAA and OGSS technique to perform anti aliasing. In general, rendering using FAA is faster than using OGSS

  7. A prospective study of anti-chromatin and anti-C1q autoantibodies in patients with proliferative lupus nephritis treated with cyclophosphamide pulses or azathioprine/methylprednisolone

    NARCIS (Netherlands)

    Grootscholten, Cecile; Dieker, Jurgen W. C.; McGrath, Fabian D.; Roos, Anja; Derksen, Ronald H. W. M.; van der Vlag, Jakob; Daha, Mohamed R.; Berden, Jo H. M.

    2007-01-01

    Objective: To study the prevalence and course of anti-chromatin (anti-nucleosome, anti-double-stranded (ds) DNA and anti-histone) and anti-C1q autoantibodies in patients with proliferative lupus nephritis (LN), treated in a randomised controlled trial with either cyclophosphamide or azathioprine

  8. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    Science.gov (United States)

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  9. Anti-dsdna, anti-smith y anti-la: Factores de riesgo y pronóstico de nefritis lúpica

    OpenAIRE

    Roberto Ferro; Francisco Medina; Demetrio Serracín

    2006-01-01

    Introducción:La nefritis lúpica es una manifestación común y de mal pronóstico en pacientes con lupus eritematoso sistémico. Diferentes; autoanticuerpos han mostrado relación con la aparición nefritis lúpica pero los resultados son controversiales. En la presente investigación; se estudian los factores inmunológicos asociados a la aparición y grado morfológico de nefritis lúpica, tales como el anticuerpo anti-dsDNA,; anti-Sm, anti-Ro y anti-La y anti-RNP. Materiales y Métodos:Estudio...

  10. 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.

  11. Violation of Particle Anti-particle Symmetry

    CERN Multimedia

    CERN. Geneva

    2001-01-01

    Symmetry is a fundamental concept which can be found in the whole range of human activities e. g. from arts to science. The beauty of a statues is often related to its symmetric form. In physics, all the laws are related to some sort of symmetry. Equally important is a small breakdown ofsymmetry. Even for the case of a statue, its beauty might be enhanced by introducing small distortions. In this course, we investigate the role symmetry in the world of elementary particles. Some symmetries found there are very similar to those which can be seen in our daily life, while others are more exotic and related to the quantum nature of the elementary particles. Our particular focus ismade on symmetry and its violation between the matter and anti-matter, known as CP violation. It is experimentally well established that particleand anti-particle behave a tiny bit differently in the world of elementary particles. We discuss how this would be explained and how we can extendour knowledge. Evolution of our universe is stro...

  12. Anti-idling campaign : Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-11-01

    The efficient use of transportation fuels and other petroleum products is being promoted by the Canadian Petroleum Products Institute. The Institute was busy during the past year in attempting to gain an understanding of the measures that could be adopted to assist motorists clearly identify the relationship between fuel consumption, personal transportation spending, and environmental impacts. The Institute undertook these efforts with Natural Resources Canada (NRCan) Office of Energy Efficiency (which both provided funding) and the Public Policy Forum. A first step proposed was the development of an anti-idling public awareness campaign. It was recognized that idling a vehicle for more than ten seconds costs money and wastes fuel, while simultaneously contributing to air pollution, greenhouse gas emissions, and climate change. The campaign also involved Esso, Shell, Petro-Canada, Canadian Tire and Sunoco for the development and implementation phases over the last two weeks of August 2002. A pilot campaign was tested in Mississauga, Ontario. Various materials were used for this campaign, such as posters, banners, cling vinyl window decals, air fresheners and information cards. The main successes of the campaign were: testing the methods of communicating the anti-idling message to drivers at gasoline retailing sites, increasing awareness among the driving public concerning the problems resulting from excessive idling, and encouraging the reduction of idling whenever and wherever it takes place. 1 tab.

  13. [Omalizumab: Beyond anti-IgE properties].

    Science.gov (United States)

    Perotin, J-M; Barnig, C

    2017-02-01

    Omalizumab is used as a treatment for severe allergic asthma. Its intended mechanism of action is based on its anti-IgE proprieties. However, recent studies have highlighted other mechanisms of action. Omalizumab treatment is associated with a decrease in the number of dendritic cells, T and B lymphocytes and eosinophils. This anti-inflammatory activity is characterized by a decrease in the levels of several cytokines involved in the recruitment, activation and survival of eosinophils and mastocytes, and in a Th2 orientation of the immune response. A modulation of bronchial remodeling by omalizumab has recently been shown. A decrease in the production of extracellular matrix components and in the proliferation of smooth muscle cells could be involved in this modulation. These mechanisms of action could explain in part the clinical efficiency of omalizumab in non-allergic conditions such as non-allergic asthma, non-allergic urticaria or nasal polyposis. A precise knowledge of the mechanisms of action of omalizumab could allow the identification of biomarkers predictive of efficacy of this treatment. These could be useful tools in the phenotyping of severe asthma. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. Optical enhancing durable anti-reflective coating

    Science.gov (United States)

    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.

  15. 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.

    2017-06-27

    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.

  16. 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.

  17. Anti-inflammatory potential of silk sericin.

    Science.gov (United States)

    Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

    2013-04-01

    Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

  18. Anti-Trypanosoma cruzi activity of nicotinamide.

    Science.gov (United States)

    Soares, Milena B P; Silva, Cinara V; Bastos, Tanira M; Guimarães, Elisalva T; Figueira, Claudio P; Smirlis, Despina; Azevedo, Walter F

    2012-05-01

    Inhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in the vacuolization in the cytoplasm were observed in epimastigotes treated with nicotinamide. Analysis of the complex of Sir2 and nicotinamide revealed the details of the possible ligand-target interaction. Our data reveal a potential use of TcSir2 as a target for anti-T. cruzi drug discovery. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Compensatory anti-inflammatory response syndrome.

    Science.gov (United States)

    Adib-Conquy, Minou; Cavaillon, Jean-Marc

    2009-01-01

    The concept of 'Compensatory anti-inflammatory response syndrome' (CARS) was proposed in 1997 by Roger Bone (1941-1997) to qualify the consequences of the counter-regulatory mechanisms initiated to limit the overzealous inflammatory process in patients with infectious (sepsis) or non-infectious systemic inflammatory response syndrome (SIRS). One major consequence of CARS is the modification of the immune status that could favour the enhanced susceptibility of intensive care patients to nosocomial infections. Indeed, most animal 'two-hit' models illustrate an enhanced sensitivity to infection after a first insult. However, this observation is highly dependent on the experimental procedure. Numerous functions of circulating leukocytes are altered in sepsis and SIRS patients, as well as in animal models of sepsis or SIRS. However, this is rather a reprogramming of circulating leukocytes, since there is not a global defect of the immune cells functions. Furthermore, within tissues, leukocytes are rather primed or activated than immunosuppressed. Thus, CARS may be considered as an adapted compartmentalized response with the aim to silence some acute proinflammatory genes, and to maintain the possible expression of certain genes involved in the anti-infectious process.

  20. Immunomodulatory effects of anti-microbial peptides.

    Science.gov (United States)

    Otvos, Laszlo

    2016-09-01

    Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro- and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

  1. Hawkmoths produce anti-bat ultrasound

    Science.gov (United States)

    Barber, Jesse R.; Kawahara, Akito Y.

    2013-01-01

    Bats and moths have been engaged in aerial warfare for nearly 65 Myr. This arms race has produced a suite of counter-adaptations in moths, including bat-detecting ears. One set of defensive strategies involves the active production of sound; tiger moths' ultrasonic replies to bat attack have been shown to startle bats, warn the predators of bad taste and jam their biosonar. Here, we report that hawkmoths in the Choerocampina produce entirely ultrasonic sounds in response to tactile stimulation and the playback of biosonar attack sequences. Males do so by grating modified scraper scales on the outer surface of the genital valves against the inner margin of the last abdominal tergum. Preliminary data indicate that females also produce ultrasound to touch and playback of echolocation attack, but they do so with an entirely different mechanism. The anti-bat function of these sounds is unknown but might include startling, cross-family acoustic mimicry, warning of unprofitability or physical defence and/or jamming of echolocation. Hawkmoths present a novel and tractable system to study both the function and evolution of anti-bat defences. PMID:23825084

  2. 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. Copyright © 2013. Published by Elsevier B.V.

  3. Assessment of the anti-angiogenic, anti-inflammatory and antinociceptive properties of ethyl vanillin.

    Science.gov (United States)

    Jung, Hyun-Joo; Song, Yun Seon; Kim, Kyunghoon; Lim, Chang-Jin; Park, Eun-Hee

    2010-02-01

    The present work aimed to assess novel pharmacological properties of ethyl vanillin (EVA) which is used as a flavoring agent for cakes, dessert, confectionary, etc. EVA exhibited an inhibitory activity in the chorioallantoic membrane angiogenesis. Anti-inflammatory activity of EVA was convinced using the two in vivo models, such as vascular permeability and air pouch models in mice. Antinociceptive activity of EVA was assessed using acetic acid-induced writhing model in mice. EVA suppressed production of nitric oxide and induction of inducible nitric oxide synthase in the lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells. However, EVA could not suppress induction of cyclooxygenase-2 in the LPS-activated macrophages. EVA diminished reactive oxygen species level in the LPS-activated macrophages. EVA also suppressed enhanced matrix metalloproteinase-9 gelatinolytic activity in the LPSactivated RAW264.7 macrophage cells. EVA at the used concentrations couldn't diminish viability of the macrophage cells. Taken together, the anti-angiogenic, anti-inflammatory and anti-nociceptive properties of EVA are based on its suppressive effect on the production of nitric oxide possibly via decreasing the reactive oxygen species level.

  4. anti-inflammatory and anti-oxidant effects of sterculia tragacantha ...

    African Journals Online (AJOL)

    Rita

    2013-02-06

    Feb 6, 2013 ... Key words: Fractions, edema, granuloma, anti-oxidant, S. tragacantha. INTRODUCTION. Inflammation is a biologic process initiated by noxious stimuli such as chemical injury, trauma or surgery. (O'Byrne and Dalgleish, 2001). This biologic response protects the host and heals damaged tissues after an.

  5. Anti-Inflammatory and Anti-Nociceptive Effects of Ethanolic Extract of ...

    African Journals Online (AJOL)

    The ethanolic stembark extract of M .africana (30-90 mg/kg) was investigated for pharmacological properties against egg white albumin - induced inflammation, Chemical as well as thermal- induced pain as well as yeast induced pyresis in rats. The extract demonstrated a dose – dependent anti- inflammatory ...

  6. Anti-inflammatory and anti-nociceptive effects of ethanolic extract of ...

    African Journals Online (AJOL)

    The ethanolic leaf extract of Setaria megaphylla (100-300 mg/kg) was investigated for pharmacological properties against egg white albumin - induced inflammation, Chemical as well as thermal- induced pain. The extract demonstrated a dose – dependent anti- inflammatory and antinociceptive activities. These activities ...

  7. 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

  8. 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.

  9. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D.

    NARCIS (Netherlands)

    Kapur, R.; Della Valle, L.; Verhagen, O.J.; Hipgrave Ederveen, A.; Ligthart, P.; de Haas, M.; Kumpel, B.; Wuhrer, M.; van der Schoot, C.E.; Vidarsson, G.

    2015-01-01

    Background RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions

  10. Prophylactic anti-D preparations display variable decreases in Fc-fucosylation of anti-D

    NARCIS (Netherlands)

    Kapur, Rick; Della Valle, Luciana; Verhagen, Onno J. H. M.; Hipgrave Ederveen, Agnes; Ligthart, Peter; de Haas, Masja; Kumpel, Belinda; Wuhrer, Manfred; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    RhIG is obtained from hyperimmunized healthy anti-D donors (HIDs) boosted with D+ red blood cells (RBCs). One hypothesis for its mechanism of action is fast clearance of opsonized D+ RBCs through Fcγ receptor (FcγR)III. Levels of immunoglobulin (Ig)G Fc-fucosylation influence interactions with

  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-Nociceptive And Anti-Inflammatory Effects Of A Nigerian ...

    African Journals Online (AJOL)

    PHT anti-inflammatory effect was elucidated to be significantly (p<0.05) mediated via histaminergic, serotonergic, bradykinin and prostaglandin inhibition. PHT was also shown to be more protective than acetylsalicylic acid (ASA) in the castor oil- induced diarrhea model, which suggests the involvement of other mechanisms.

  13. Studies on the anti-inflammatory and anti-nociceptive properties of Blepharis maderaspatensis leaves

    Directory of Open Access Journals (Sweden)

    Abimbola Sowemimo

    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.

  14. 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

  15. Cytotoxic, anti-cancer, and anti-microbial effects of different extracts obtained from Artemisia rupestris.

    Science.gov (United States)

    Nokerbek, Shamshabanu; Sakipova, Zuriyadda; Chalupová, Marta; Nejezchlebová, Marcela; Hošek, Jan

    2017-01-01

    Artemisia rupestris is a part of traditional Kazakh folk medicine. Extracts obtained from this plant are used to treat various diseases, including cancer. This study evaluates the anti-microbial, cytotoxic, and anti-cancer effects of different extracts of the plant. Different extraction techniques were used and the resultant activities were compared. Extracts of A. rupestris were prepared from the flowers plus the leaves and from the stems. The antimicrobial activity against Candida albicans and Staphylococcus aureus was quantified. Cell lines L1210 and THP-1 were used to evaluate the cytotoxic potential of these extracts in vitro. The anti-cancer effect was tested using L1210-induced tumorgenesis in mouse model. The aqueous extract of stems was the most active against C. albicans, whereas the methanolic extract of flowers plus leaves especially inhibited the growth of S. aureus. The aqueous extracts were found to be non-cytotoxic for both cell lines, whereas the lipophilic extracts showed cytotoxic effects. The extract obtained from flowers plus leaves was more cytotoxic than that from stems. The tested extracts showed no anti-cancer potential. The results obtained testify to the relatively safe consumption of aqueous extracts of A. rupestris, but lipophilic extracts showed toxic effects and their consumption should be considered more carefully.Key words: L1210 cell line THP-1 cell line microwave-assisted extraction ultrasonic-assisted extraction Candida albicans Staphylococcus aureus.

  16. Anti-leishmanial and Anti-cancer Activities of a Pentacyclic ...

    African Journals Online (AJOL)

    Purpose: Terminalia arjuna Roxb (Combretaceae) is commonly known as Arjjhan and Arjun in Bengal, India. The anti-leishmanial and anticancer activities of a pentacyclic triterpenoid isolated from its leaves were evaluated. Methods: Dried and crushed leaves of Terminalia arjuna were de-fatted with petroleum ether ...

  17. Anti-diabetic and anti-oxidant effects of Zingiber Officinale on ...

    African Journals Online (AJOL)

    This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic ...

  18. Anti-inflammatory, anti-hyperalgesic, antiplatelet and antiulcer activities of Byrsonima japurensis A. Juss. (Malpighiaceae).

    Science.gov (United States)

    Guilhon-Simplicio, Fernanda; Pinheiro, Carlos Cleomir de Souza; Conrado, Gabrielly Galdino; Barbosa, Gleyce Dos Santos; Santos, Pierre Alexandre Dos; Pereira, Maria de Meneses; Lima, Emerson Silva

    2012-03-27

    Decoctions or infusions of the stem bark of Byrsonima japurensis A. Juss. (Malpighiaceae) are widely used as an anti-inflammatory drug in folk medicine of Amazonas State (Brazil). To evaluate the pharmacological potential of an aqueous extract of the stem bark of Byrsonima japurensis (BJEA) to scientifically verify of its traditional use. Anti-inflammatory, antihyperalgesic and antiulcer activities were evaluated in Wistar rats, a Hippocratic screening was performed in Swiss mice to evaluate the toxic effects, and antiplatelet evaluation was performed in human platelet rich plasma assay. Additionally, antioxidant activity was evaluated by superoxide radical scavenging method and β-carotene bleaching test. Anti-inflammatory, antihyperalgesic and gastroprotective activities were observed in rats treated orally with different doses of BJEA. While signals of toxicity were observed in the mice treated with a very high dose of extract (5000mg/kg), no death occurred. BJEA also showed expressive antiplatelet and antioxidant activities in vitro. According to our results, it was concluded that stem bark of Byrsonima japurensis has significant and safe anti-inflammatory activity, which is closely related with their potent antioxidant activity, supporting the folk medicinal use of this species. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Anti-inflammatory and anti-nociceptive activities of Sipunculus nudus L. extract.

    Science.gov (United States)

    Zhang, Chen-Xiao; Dai, Zi-Ru; Cai, Qiu-Xing

    2011-10-11

    Sipunculus nudus has long been employed as traditional Chinese medicine in folk remedies for the treatment of carbuncles, tuberculosis and nocturia, regulating the functions of stomach and spleen, as well as for the restoration to health in debilities caused by various pathogens and aging. Decoction of Sipunculus nudus has traditionally been used to remedy sternalgia in folk medicine. This study aimed to assess the anti-inflammatory and anti-nociceptive activity of the water extract from Sipunculus nudus. The water extract from the body wall of Sipunculus nudus was obtained with the yield of 14.1%. The anti-inflammatory effect in six animal models and anti-nociceptive effect in two animal models of the water extract were evaluated by oral for the study. Pretreatment with the extract (at the dose of 50, 100 and 200 mg/kg) produced significant dose-dependent anti-inflammatory and anti-nociceptive effects. At 200 mg/kg dose, the inhibition ratio of the extract on carrageenan-induced rat hind paw oedema, dextran-induced rat paw oedema, cotton pellet granuloma in rats, carrageenan-induced peritonitis and acetic acid-induced vascular permeability were 59.2%, 51.0%, 53.1%, 42.5%, 50.8%, better than that of indomethacin (5 mg/kg) 49.5%, 50%, 44.4%, 37.6%, 46.8%, respectively. The inhibition ratio of the extract (200 mg/kg dose) on xylene-induced mouse ear oedema was 61.5%, lower than 63.7% for indomethacin (5 mg/kg). At 200mg/kg, the extract decreased number of writhing 52.3% in acetic acid-induced writhing model and increased the response latency 25.24% in hot plate test. The water extract from the body wall of Sipunculus nudus possesses excellent anti-inflammatory activity as well as peripheral and central analgesic properties. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

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

    Science.gov (United States)

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

    2016-01-01

    Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro . The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro , suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study

  2. [Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

    Science.gov (United States)

    Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

    1982-08-01

    Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals.

  3. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    Science.gov (United States)

    Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

    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-α mRNA 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-α mRNA 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. PMID:25182441

  4. 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.

  5. Walloons as General or Specific Others? A Comparison of anti-Walloon and anti-immigrant Attitudes in Flanders

    Directory of Open Access Journals (Sweden)

    Bart Meuleman

    2017-11-01

    Full Text Available This study attempts to shed light on the structure, the prevalence and the determinants of anti-Walloon attitudes in Flanders. For this purpose, we contrast anti-Walloon prejudice with prejudice against a relatively well-understood and archetypical out-group, namely immigrants. Our theoretical approach draws on insights from two paradigms of intergroup relations: the Group-Focused Enmity approach stressing that specific prejudices have a strong common denominator, and the Differentiated Threat model arguing that specific prejudices are contingent on the context of intergroup relations as well as the involved types of threat. To assess the (dissimilarities in anti-Walloon and anti-immigrant prejudice, we use the Flemish dataset of the Belgian National Election Study (BNES 2010. Comparable measurement instruments for both forms of prejudice are analyzed by means of structural equation modeling. Our results reveal a nuanced picture regarding the similarities and differences between anti-Walloon and anti-immigrant attitudes in Flanders. One the one hand, anti-Walloon and anti-immigration attitudes are strongly correlated and rooted in economic threat perceptions. On the other hand, anti-Walloon attitudes are less outspoken in the Flemish population than anti-immigrant attitudes, are less founded on cultural threat perceptions and are more closely linked to feelings of identification with the Flemish in-group.

  6. LEMBAGA PENDIDIKAN ISLAM SEBAGAI WAHANA IMPLEMENTASI PENDIDIKAN ANTI KORUPSI

    Directory of Open Access Journals (Sweden)

    Much. Arif Saiful Anam

    2015-11-01

    Full Text Available It has widely spread among either central or local government officials. Hence, it is crucial to build the awareness of all parties to combat, eliminate, and fight any kinds of corruption The spirit of anti-corruption that should be studied are building a mindset, an attitude, and anti-corruption behavior through school where a civilizing prosess occurs. Thus, formal education sector in Indonesia can play a role in meeting the needs of the prevention of corruption. There are two indirect preventive approaches. Firstly, set the learners as a target, and secondly empower learners to influence the society against corruption. Implementation of anti-corruption education in Madrasah should be able to create a conducive situation to reach a free of corruption environment and build generations of anti corruption. It can break the corruption chain. The main strategy of anti-corruption education in Indonesia can be run through implenting anti-corruption action in Madrasah.

  7. Serious adverse events reported for anti-obesity medicines

    DEFF Research Database (Denmark)

    Aagaard, L; Hallgreen, C E; Hansen, Ebba Holme

    2016-01-01

    BACKGROUND: Use of anti-obesity medicines has been linked with serious cardiac and psychiatric adverse events (AEs). Spontaneous reports can provide information about serious, rare and unknown AEs occurring after time of marketing. In Europe, information about AEs reported for anti-obesity medici......BACKGROUND: Use of anti-obesity medicines has been linked with serious cardiac and psychiatric adverse events (AEs). Spontaneous reports can provide information about serious, rare and unknown AEs occurring after time of marketing. In Europe, information about AEs reported for anti......-obesity medicines can be accessed in the EudraVigilance database (EV). Therefore, we aimed to identify and characterise adverse events (AEs) associated with use of anti-obesity medicines in Europe. METHODS: AE reports submitted for anti-obesity medicines (Anatomical Therapeutic Chemical [ATC] group A08A) from 2007...

  8. Human anti-animal antibody interferences in immunological assays.

    Science.gov (United States)

    Kricka, L J

    1999-07-01

    The scope and significance of human anti-animal antibody interference in immunological assays is reviewed with an emphasis on human anti-animal immunoglobulins, particularly human anti-mouse antibodies (HAMAs). Anti-animal antibodies (IgG, IgA, IgM, IgE class, anti-isotype, and anti-idiotype specificity) arise as a result of iatrogenic and noniatrogenic causes and include human anti-mouse, -rabbit, -goat, -sheep, -cow, -pig, -rat, and -horse antibodies and antibodies with mixed specificity. Circulating antibodies can reach gram per liter concentrations and may persist for years. Prevalence estimates for anti-animal antibodies in the general population vary widely and range from HAMA, which causes both positive and negative interferences in two-site mouse monoclonal antibody-based assays. Strategies to prevent the development of human anti-animal antibody responses include immunosuppressant therapy and the use of humanized, polyethylene glycolylated, or Fab fragments of antibody agents. Sample pretreatment or assay redesign can eliminate immunoassay interferences caused by anti-animal antibodies. Enzyme immunoassays, immunoradiometric assays, immunofluorescence, and HPLC assays have been designed to detect HAMA and other anti-animal antibodies, but intermethod comparability is complicated by differences in assay specificity and lack of standardization. Human anti-animal antibodies often go unnoticed, to the detriment of patient care. A heightened awareness on the part of laboratory staff and clinicians of the problems caused by this type of interference in routine immunoassay tests is desirable. Efforts should be directed at improving methods for identifying and eliminating this type of analytical interference.

  9. Anti-corruption trainig programs in center and eastern Europe

    OpenAIRE

    bryane michael

    2005-01-01

    Drawing upon the work of the NISPAcee Working Group on Preventing Corruption in Public Administration, this book reviews the current state of anti-corruption training and education in Central and Eastern Europe. Original data and analysis from anti-corruption trainers and policymakers from over 7 countries in the region -- Kosovo, Latvia, Lithuania, Poland, Russian Federation, Serbia, Ukraine, and others -- is assembled into the compilation. Each country analysis reviews anti- corruption legi...

  10. [Detection and analysis of anti-Rh blood group antibodies].

    Science.gov (United States)

    Wu, Yuan-jun; Wu, Yong; Chen, Bao-chan; Liu, Yan

    2008-06-01

    To study the prevalence and distribution of anti-Rh blood group antibodies in Chinese population and its clinical significance. Irregular antibodies were screened and identified by Microcolum Gel Coomb's test. For those identified as positive anti-Rh samples, monoclonal antibodies (anti-D, -C, -c, -E and -e) were used to identify the specific antigen and confirm the accuracy of the irregular antibody tests. The titers, Ig-types and 37 Degrees Celsius-reactivity were tested to confirm its clinical significance. For evaluation of the origin of irregular antibodies, histories of pregnancy and transfusion were reviewed. For the newborns who had positive antibodies, their mothers were tested simultaneously to confirm the origin of the antibodies. 47 out of 54 000 (0.087%) patients were identified as positive with Rh blood group antibodies.Of them, 27 cases had history of pregnancy, 13 had transfusion and 1 had the histories of both. 6 newborns had antibodies derived form their mothers. The specificity of the antibody was as follows: 29 with anti-E (61.70%), 8 with anti-D (17.02%), anti-cE 5(10.64%), 4 with anti-c (8.51%) and 1 with anti-C (2.13%). All the 47 Rh blood group antibodies were IgG or IgG+IgM, and were reactive to red blood cells with corresponding antigens at 37 Degrees Celsius, with a highest titer of 1:4 096. The prevalence of Rh antibodies is lower in Chinese population as compared with that in White population.Of all the antibodies, anti-E is most frequently identified and anti-D was declining. Alloimmunization by pregnancy and transfusion is the major cause of Rh antibody production. Rh blood group antibodies derived from mothers are the major cause of Non-ABO-HDN.

  11. Medicinal herbs as possible sources of anti-inflammatory products

    Directory of Open Access Journals (Sweden)

    Andreia Corciovă

    2017-12-01

    Full Text Available Plants constitute an inexhaustible source of bioactive compounds that can be valuable for research in the chemistry field of anti-inflammatory compounds. This review describes several plants from international and national flora that have been shown to have anti-inflammatory activity in various clinical trials. The paper includes: general aspects regarding the vegetal source, compounds responsible for anti-inflammatory activity, mechanism of action and clinical trials carried out with extracts or products containing standardized extracts.

  12. Anti-Money Laundering Requirements – Perceived Effectiveness

    OpenAIRE

    C. C. Huang; M. S. Amirrudin; N. A. Ahamad Noruddin; R. Othman

    2013-01-01

    Anti-money laundering is commonly recognized as a set of procedures, laws or regulations designed to reduce the practice of generating income through illegal actions. In Malaysia, the government and law enforcement agencies have stepped up their capacities and efforts to curb money laundering since 2001. One of these measures was the enactment of the Anti-Money Laundering Act (AMLA) in 2001. The implementation costs on anti-money laundering requirements (AMLR) can be burd...

  13. Pendidikan Anti Korupsi Bagi Siswa Sekolah Dasar di Kecamatan Gunungpati

    OpenAIRE

    Suciptaningsih, Oktaviani Adhi

    2014-01-01

    Schools can take a strategic role in the implementation of anti-corruption education, especially in a culture of anti-corruption behavior among students. This study has the objective to know the anti-corruption education for elementary school students in the Kecamatan Gunungpati. This research was conducted using qualitative methods, descriptive analytical. Data collection techniques used were interviews, observation and documents. Analysis of data using qualitative research phases according ...

  14. The automotive anti-collision system based on Ultrasonic

    Directory of Open Access Journals (Sweden)

    Qi Qinqin

    2017-08-01

    Full Text Available In the existing system of automobile anti-collision,the radar is mainly used for ranging.However,it can't be widely used because of its high cost.In this paper,based on the existing system of automobile anti-collision,the ultrasonic sensor is used to measure the distance and establish relevant anti-collision model.The experimental results show that the alarming information is accurate within a certain range.

  15. EU Anti-Circumvention Rules: Do They Beat the Alternative?

    OpenAIRE

    Edwin Vermulst

    2015-01-01

    This article discusses EU law and practice with regard to tackling circumvention of trade defence instruments, notably anti-dumping measures. The author considers that, while strong legal arguments can be made that anti-circumvention rules are WTO-illegal, as a practical matter transparent and predictable anti-circumvention rules are to be preferred over vague and multi-interpretable non-preferential origin rules that vary from country to country. Furthermore, the many findings of transhipmen...

  16. Assessing anti-American sentiment through social media analysis

    OpenAIRE

    Morales, David J.

    2016-01-01

    Approved for public release; distribution is unlimited This thesis examines the history of anti-Americanism as both a passing sentiment and an enduring ideology and how both can be detrimental to American security and future prosperity. It further explores the analytical methods for studying anti-Americanism, to include classic polling and social media analysis in an attempt to determine the reliability of each. This work attempts to bring to light the underlying motives for anti-American ...

  17. Pengujian Dan Analisa Anti Komputer Forensik Menggunakan Shred Tool

    OpenAIRE

    Budi Rahardjo; I Putu Agus Eka Pratama

    2016-01-01

    Computer forensics and anti computer forensics are two opposing fields. Computer forensics is done by a computer forensics expert in order to obtain accurate data and evidence of cyber crime cases for investigation, while the anti-computer forensics conducted by the attacker to remove traces at once difficult computer forensics expert in performing its duties. For the attacker, the selection of anti-computer forensics tool that default on the target machine, more effective and faster than ins...

  18. Anti-Kählerian Geometry on Lie Groups

    Science.gov (United States)

    Fernández-Culma, Edison Alberto; Godoy, Yamile

    2018-03-01

    Let G be a Lie group of even dimension and let ( g, J) be a left invariant anti-Kähler structure on G. In this article we study anti-Kähler structures considering the distinguished cases where the complex structure J is abelian or bi-invariant. We find that if G admits a left invariant anti-Kähler structure ( g, J) where J is abelian then the Lie algebra of G is unimodular and ( G, g) is a flat pseudo-Riemannian manifold. For the second case, we see that for any left invariant metric g for which J is an anti-isometry we obtain that the triple ( G, g, J) is an anti-Kähler manifold. Besides, given a left invariant anti-Hermitian structure on G we associate a covariant 3-tensor 𝜃 on its Lie algebra and prove that such structure is anti-Kähler if and only if 𝜃 is a skew-symmetric and pure tensor. From this tensor we classify the real 4-dimensional Lie algebras for which the corresponding Lie group has a left invariant anti-Kähler structure and study the moduli spaces of such structures (up to group isomorphisms that preserve the anti-Kähler structures).

  19. Investigation of antibacterial and anti-cancer activities of ...

    African Journals Online (AJOL)

    Investigation of antibacterial and anti-cancer activities of Streptomyces sp SRF1 culture filtrate. Kusavadee Sangdee, Benjaporn Buranrat, Prapairat Seephonkai, Nilawan Surapong, Aphidech Sangdee ...

  20. 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 incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe....

  1. Optimization and anti-optimization of structures under uncertainty

    National Research Council Canada - National Science Library

    Elishakoff, Isaac; Ohsaki, Makoto

    2010-01-01

    The volume presents a collaboration between internationally recognized experts on anti-optimization and structural optimization, and summarizes various novel ideas, methodologies and results studied over 20 years...

  2. Anti-inflammatory and analgesic activities: Chemical constituents of ...

    African Journals Online (AJOL)

    Anti-inflammatory and analgesic activities: Chemical constituents of essential oils of Ocimum gratissimum , Eucalyptus citriodora and Cymbopogon giganteus inhibited lipoxygenase L-1 and cyclooxygenase of PGHS.

  3. Mediale Zukunft : die Erreichbarkeit des (Anti-)Utopischen

    OpenAIRE

    Orth, Dominik

    2009-01-01

    Während die Erforschung der politischen und literarischen Utopien und Anti-Utopien im wissenschaftlichen Diskurs nach wie vor eine große Rolle spielt, wurde die Analyse von utopischen und anti-utopischen Aspekten im Medium Film bislang vernachlässigt. Eine mögliche Ursache könnte sein, dass die Existenz von genuinen filmischen (Anti-)Utopien bezweifelt werden kann. Seit der Verlagerung der literarischen (Anti-)Utopien vom Raum in die Zeit ist die Darstellung von Gesellschaftsmodellen zumeist ...

  4. Weight Gain and Hair Loss during Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Abdo Lutf

    2012-01-01

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

  5. 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

  6. Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet.

    Science.gov (United States)

    Granito, A; Zauli, D; Muratori, P; Muratori, L; Grassi, A; Bortolotti, R; Petrolini, N; Veronesi, L; Gionchetti, P; Bianchi, F B; Volta, U

    2005-04-01

    Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.

  7. Les mondes des anti-Monde.

    Directory of Open Access Journals (Sweden)

    Jacques Lévy

    2002-05-01

    Full Text Available Ce qu’il est convenu d’appeler le « mouvement anti-mondialisation » ( Mam est un ensemble complexe de discours et d’actions. Je l’ai très modestement approché par la lecture de deux ans (janvier 1999-janvier 2001 du Monde Diplomatique , un mensuel qui apparaît assez centrale sur cet objet. D’une part, ses éditions française et étrangères sont très diffusées dans les milieux liés à ce mouvement. D’autre part, c’est de la rédaction de cette publication qu’est ...

  8. Anti-fungal activity of irradiated chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Pham ThiLe Ha; Tran Thi Thuy; Nguyen Quoc Hien [Nuclear Research Inst., No.1 Nguyen Tu Luc, Dalat (Viet Nam); Nagasawa, Naotsugu; Kume, Tamikazu [Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Gunma (Japan)

    1999-09-01

    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 {gamma}-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 {mu}g/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)

  9. Anti-racist innovation and nurse education.

    Science.gov (United States)

    Cortis, J; Law, I G

    2005-04-01

    The focus on institutional racism within the Higher Education (HE) sector in the United Kingdom and nurse education, in particular, has so far been seriously lacking in investigation and scrutiny. The Race Relations (Amendment) Act (RRAA2000) has pushed institutional racism to the forefront of debates in public services, including both education and health services. This paper seeks to operationalise some key aspects of the debate over institutional racism and relates it to both these sectors. Based on empirical work funded by the Higher Education Funding Council for England and Wales (HEFCE) Innovations Project, this paper offers nurse education a framework to not only comply with the legal requirement of 'promoting racial harmony' (RRAA 2000) and the expectations from nursing as enshrined in the Code of Professional Conduct (NMC, 2000. The Code of Professional Conduct: Protecting the Public Through Professional Standards. NMC, London), but goes further to consider some key questions for anti-racist interventions.

  10. ETHICS in GOVERNMENT: ANTI-CORRUPTION MEASURES

    Directory of Open Access Journals (Sweden)

    Coskun Can Aktan

    2015-07-01

    Full Text Available Unethicalbehavior in government is viewed as a situation where there isfraudulent or dishonest conduct or improper behaviour by people who are in aposition or power. Bribery, extortion, embezzlement,the use of legislated powersby government officials for illegitimate private gain, nepotism, rent seeking etc.are some examples forunethical behavior in government.How to deal with unethical behavior in government?. How to curb corruption?Experience demonstrates that establishing an ethical government is not an easytask. There is no single approach to curb (political corruption effectively. Instead,controlling (political corruption requires a wide range of strategies.Thisdescriptive survey aims to explore the anti-corruptions measures in general.

  11. Helicopter Anti-Torque System Using Strakes

    Science.gov (United States)

    Kelley, H. L.; Wilson, J. C.; Phelps, A. E. (Inventor)

    1984-01-01

    A helicopter is disclosed with a system for controlling main-rotor torque which reduces the power and size requirements of conventional anti-torque means. The torque countering forces are generated by disrupting the main rotor downwash flowing around the fuselage. The downwash flow is separated from the fuselage surface by a strake positioned at a specified location on the fuselage. This location is determined by the particular helicopter wash pattern and fuselage configuration, generally being located between 20 deg before top dead center (TDC) and 80 deg from TDC on the fuselage side to which the main rotor blade approaches during rotation. The strake extends along the fuselage from the cabin section to the aft end and can be continuous or separated for aerodynamic surfaces such as a horizontal stabilizer.

  12. The Anti-Ballistic Missile Treaty

    International Nuclear Information System (INIS)

    Platt, A.

    1991-01-01

    This paper reports that in late May 1972 former President Richard M. Nixon went to Moscow and signed, among other documents, a Treaty to Limit Anti-Ballistic Missile (ABM) Systems. Under this agreement, both the United States and the Soviet Union made a commitment not to build nationwide ABM defenses against the other's intercontinental and submarine-launched ballistic missiles. They agreed to limit ABM deployments to a maximum of two sites, with no more than 100 launchers per site. Thirteen of the treaty's sixteen articles are intended to prevent any deviation from this. In addition, a joint Standing Consultative Commission to monitor compliance was created. National technical means --- sophisticated monitoring devices on land, sea, and in space --- were to be the primary instruments used to monitor compliance with the treaty. The ABM Treaty was signed in conjunction with an Interim Agreement to Limit Strategic Offensive Arms

  13. Polynucleotides encoding anti-sulfotyrosine antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R [Berkeley, CA; Kehoe, John [Saint Davids, PA; Bradbury, Andrew M [Santa Fe, NM

    2011-01-11

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  14. Review of Anti-Inflammatory Herbal Medicines

    Directory of Open Access Journals (Sweden)

    Mona Ghasemian

    2016-01-01

    Full Text Available Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil’s claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle.

  15. Anti-adhesive properties of fish tropomyosins

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Bernbom, Nete; Gram, Lone

    2008-01-01

    Aims: We have recently found that preconditioning of stainless steel surfaces with an aqueous fish muscle extract can significantly impede bacterial adhesion. The purpose of this study was to identify and characterize the primary components associated with this bacteria-repelling effect. Methods...... to the formation of a proteinaceous conditioning film composed primarily of fish tropomyosins. These fibrous proteins formed a considerable anti-adhesive conditioning layer on and reduced bacterial adhesion to several different materials including polystyrene, vinyl plastic, stainless steel and glass. The protein...... the importance of substratum's physiochemical properties and exposure time with regards to protein adsorption/elution efficiency and subsequent bacterial adhesion. Significance and Impact of the Study: Fish tropomyosin-coatings could potentially offer a nontoxic and relatively inexpensive measure of reducing...

  16. Preparing Teachers for Anti-oppressive Education

    DEFF Research Database (Denmark)

    Baber, Sikunder Ali

    2004-01-01

    While theories and recommendations continue to proliferate in the educational research literature on what it means to teach towards social justice and to prepare teachers for such teaching, so do concerns that these theories and recommendations fail to account for the ways that the contexts...... of teaching cultural contexts, national contexts, political contexts always affect teaching in idiosyncratic, unpredictable and even contradictory ways. Given that much educational research fails to trouble the US-centric nature of prevailing conceptions of social justice and teacher education......, it is important to learn about the unique as well as shared challenges facing teacher educators around the globe. In this article, teacher educators from Asia, Africa, North America and South America offer a sampling of initiatives in anti-oppressive teacher education; that is, initiatives to prepare teachers...

  17. Artemisinin anti-malarial drugs in China

    Directory of Open Access Journals (Sweden)

    Zongru Guo

    2016-03-01

    Full Text Available 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.

  18. ANTI-CORRUPTION MEASURES FOR CORPORATE SECURITY

    Directory of Open Access Journals (Sweden)

    Natasha Georgieva Hadji Krsteski

    2017-04-01

    Full Text Available Corporate security should commit to ethical management and raising the quality of companies and markets through improving cooperation and transparency by applying anticorruption measures such as accepting a code of ethics; respect and follow international business principles for dealing with bribery; improve their transparency - via access to information; involvement in politics to protect persons who disclose corruption cases; and improving corporate governance - through active mutual discussions on adjustment of legal regulations. Research methods used in the paper are: qualitative analysis of secondary data obtained from relevant institutions. Results obtained from the survey include fighting corruption in corporations must find a unique solution that is long-term strategy developed transparent society crucial criteria and principles to meet the political criteria by the fulfillment of anti-corruption standards; it requires continuous cooperation of public and private sector, NGOs and the general corpus of all stakeholders in the country against corruption; the lack of a legal framework or platform for establishing public and private partnerships, is an important factor for anti-corruption measures to improve corporate governance; mechanisms for cooperation does not seem sufficiently developed between the public, private, political and civil society; the most important factor to tackle corruption is to adopt a law on public prosecutors and determination of higher norms and standards. Conclusions drawn from the survey: in the area of pre-trial procedure requires shifting responsibilities of Interior Ministry body training in the area of the judicial system; it is necessary to change the Criminal Code and Criminal Procedure Code by changing certain legal provisions which refer to the Agency for money laundering SCCP, a financial police and overall legislation.

  19. Resveratrol: anti-obesity mechanisms of action.

    Science.gov (United States)

    Aguirre, Leixuri; Fernández-Quintela, Alfredo; Arias, Noemí; Portillo, Maria P

    2014-11-14

    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.

  20. ANALGESIC, ANTI-INFLAMMATORY AND ANTI-ULCER ACTIVITY OF ETHANOL AND ETHYL ACETATE EXTRACTS OF TECOMARIA CAPENSIS LEAVES

    OpenAIRE

    E. Tamil Jothi; G. Vimala Devi; Ch. Vamsi Anil Krishna; V. Suba

    2013-01-01

    In the present study ethyl acetate and ethanol extracts of leaves of Tecomaria capensis were screened for analgesic, anti-inflammatory and anti-ulcer activity. The analgesic activity was performed by two thermal models. One is hot plate method and another one is tail flick method. The two extracts of Tecomaria capensis leaves have showed analgesic activity in both methods. The anti-inflammatory activity was investigated by two methods. One is carrageenan induced paw edema method (in-vivo) and...