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  • 1.
    Ali, Abukar
    University of Skövde, School of Life Sciences.
    Time window of TNF-a in innate immunity against staphylococcal infection2010Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Staphylococcus aureus (S. aureus) is responsible for many human diseases including septic arthritis and sepsis shock. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in inflammation and produced mainly by macrophages and monocytes. It is believed to be involved in pathogenesis of septic arthritis. Time window of TNF-a in innate immunity against staphylococcal infection was studied in this project.

    Two experiments were carried out: In the first experiment mice were infected with a low dose (8x106cfu/mouse) of S. aureus to induce septic arthritis whereas in the second experiment the mice were infected with a higher dose (8x107cfu/mouse) of S. aureus to induce sepsis shock. All mice were divided into three groups. The first group was treated with anti-TNF-α 20 minutes after infection. The second group was treated with the anti-TNF-α three days after infection. The third group served as control and was injected with PBS instead of anti-TNF-α. The mice were regularly weighed and signs of arthritis and mortality were recorded. Two weeks after inoculation bacteria viable counts in different organs was done, as well as histopathological assessment of joints and measurement of cytokines in blood.

    We have observed that mice treated with anti-TNF-α had less severe arthritis and also less mortality. However, they had more bacteria accumulated in the kidneys and lost more weight compared to the control group. The results were mostly seen in the group early treated with TNF-α, compared to the late treated group.

    We conclude that anti-TNF-α might be potentially used as a therapy against septic arthritis and sepsis shock. This should be combined with antibiotics to eliminate the bacteria while the anti-TNF-α reduces the severity of the inflammation and thus reduce the risk of permanent joint destruction and mortality. We can conclude that blocking TNF-α early on is essential in order to get the best results.

  • 2.
    Jensen, Poul Erik H.
    et al.
    Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmar.
    Warnke, Clemens
    Department of Neurology, University Hospital Köln, Germany / University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Ingenhoven, Kathleen
    University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Piccoli, Luca
    Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland.
    Gasis, Marcia
    University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Hermanrud, Christina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fernandez-Rodriguez, Blanca M.
    Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland.
    Ryner, Malin
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kramer, Daniel
    Sanofi-Aventis Germany, Frankfurt Am Main, Germany.
    Link, Jenny
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Ramanujam, Ryan
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden / KTH – Royal Institute of Technology, Stockholm, Sweden.
    Auer, Michael
    Innsbruck Medical University, Innsbruck, Austria.
    Buck, Dorothea
    Department of Neurology, Technische Universität München, Munich, Germany.
    Grummel, Verena
    Department of Neurology, Technische Universität München, Munich, Germany.
    Bertotti, Elisa
    Merck NBE Bioanalytics Ivrea, Colleretto Giacosa, Italy.
    Fissolo, Nicolas
    Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain.
    Oliver-Martos, Begoña
    Hospital Regional Universitario de Málaga, Instituto de investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Spain.
    Nytrova, Petra
    MS Center, Department of Neurology and Center Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
    Khalil, Michael
    Department of Neurology, Medical University of Graz, Austria.
    Guger, Michael
    Clinic for Neurology 2, Kepler University Clinic, Med Campus III, Linz, Austria.
    Rathmaier, Sandra
    Clinic for Neurology 2, Kepler University Clinic, Med Campus III, Linz, Austria.
    Sievers-Stober, Claudia
    Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Switzerland.
    Lindberg, Raija L. P.
    Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Switzerland.
    Hässler, Signe
    CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France.
    Bachelet, Delphine
    CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France.
    Aktas, Orhan
    University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Donnellan, Naoimh
    Ipsen Biopharm Ltd., Berkshire, United Kingdom.
    Lawton, Andy
    GlaxoSmithKline R&D, Uxbridge, Middlesex, United Kingdom.
    Hemmer, Bernhard
    Department of Neurology, Technische Universität München, Germany / Munich Cluster for systems Neurology (SyNergy), Germany.
    Havrdova, Eva Kubala
    MS Center, Department of Neurology and Center Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.
    Kieseier, Bernd
    University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Hartung, Hans-Peter
    University of Düsseldorf, Medical Faculty, Department of Neurology, Germany.
    Comabella, Manuel
    Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain.
    Montalban, Xavier
    Hospital Universitari Vall d'Hebron, Centre d'Esclerosi Múltiple de Catalunya, Barcelona, Spain.
    Derfuss, Tobias
    Departments of Biomedicine and Neurology, University Hospital Basel and University of Basel, Switzerland.
    Sellebjerg, Finn
    Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
    Dönnes, Pierre
    SciCross AB, Skövde, Sweden.
    Pallardy, Marc
    INSERM UMR 996, Univ. Paris-Sud, Faculty of Pharmacy, Université Paris-Saclay, Châtenay-Malabry, France.
    Spindeldreher, Sebastian
    Drug Metabolism Pharmacokinetics-Biologics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
    Broët, Philippe
    CESP, INSERM UMR 1018, Faculty of Medicine, Paris-Sud University, Paris-Saclay, University UVSQ, Villejuif, France / Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France.
    Deisenhammer, Florian
    Innsbruck Medical University, Austria.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Sorensen, Per Soelberg
    Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
    Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis: Results from the ABIRISK prospective cohort study2019In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 326, p. 19-27Article in journal (Refereed)
    Abstract [en]

    Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.

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