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Mata S.,Azienda Ospedaliero Universitaria di Careggi | Mata S.,Neuroimmunology Laboratory | Lolli F.,Azienda Ospedaliero Universitaria di Careggi
Journal of the Neurological Sciences | Year: 2011

Neuromyelitis optica (NMO) is an inflammatory condition characterized by the selective involvement of the optic nerves and spinal cord, and by a frequent relapsing course. Many clinical, laboratory and neuroimaging studies have provided useful means to distinguish NMO from multiple sclerosis (MS). The detection of aquaporin-4 (AQP4) antibodies has broadened the spectrum of the disorder, which now includes limited variants (either recurrent myelitis or optic neuritis), Asian opticospinal MS, and "atypical" forms with brain involvement. Many in vitro and in vivo evidence have recently demonstrated that AQP4 antibody plays a relevant pathogenetic role in NMO by inducing an increase of BBB permeability, complement cascade activation and astrocytic cytotoxicity. While corticosteroids and plasma exchange are better therapeutic options during NMO attacks, other treatments should be aimed at the prevention of recurrence, possibly by targeting autoantibody production and/or effector mechanisms. Rituximab and Mofetil Mycophenolate appear at the moment the most promising drugs. Since even the most sensitive AQP4 antibody tests fail to mark about 20-30% of the NMO cases, while 20-30% of positive patients have "atypical" or MS-like variants, it remains to be clarified if NMO, as a clinical entity, can still be considered a disease rather than a syndrome, with more possible pathogenetic mechanisms. © 2011 Elsevier B.V. Source

Cutshall S.M.,Mayo Medical School | Brekke K.M.,Neuroimmunology Laboratory
Alternative Therapies in Health and Medicine | Year: 2011

Background • Postoperative pain and anxiety are common in cardiac surgery patients. Studies have suggested that music can decrease anxiety in hospitalized patients. Primary Study Objective • This study focused on the efficacy and feasibility of special music, which included nature sounds, for pain and anxiety. Methods/Design • In this randomized controlled trial, postoperative cardiovascular surgery patients were randomly assigned to a music group to receive 20 minutes of standard postoperative care and music twice daily on postoperative days 2 through 4 or to a control group to receive 20 minutes of standard care with a quiet resting period twice daily on postoperative days 2 through 4. Setting • Cardiovascular surgical unit of Saint Marys Hospital, Rochester, Minnesota. Participants • One hundred patients completed the study (music group, n = 49; control group, n = 51). Intervention • The music was delivered through CD players in the patients' rooms. Primary Outcome Measures • Pain, anxiety, satisfaction, and relaxation were evaluated from visual analog scales. Results • Data showed a significant decrease in mean (SD) pain scores after the second session of day 2 for the music group (change, -1.4 [1.4]) compared with the control group (change, -0.4 [1.4]) (P =.001). Mean relaxation scores improved more at the first session of day 2 for the music group (change, 1.9 [2.7]) compared with the control group (change, 0.3 [2.9]) (P =.03). The music group also showed lower anxiety and increased satisfaction overall, but these differences were not statistically significant. No major barriers to using the therapy were identified. Conclusion • Recorded music and nature sounds can be integrated into the postoperative care of cardiovascular surgery patients. The recordings may provide an additional means for addressing common symptoms of pain and anxiety while providing a means of relaxation for these patients. Source

Zhu Y.,University of South Florida | Obregon D.,University of South Florida | Hou H.,University of South Florida | Giunta B.,University of South Florida | And 13 more authors.
Journal of Cellular and Molecular Medicine | Year: 2011

Mutations in the presenilin-1 (PS1) gene are independent causes of familial Alzheimer's disease (AD). AD patients have dysregulated immunity, and PS1 mutant mice exhibit abnormal systemic immune responses. To test whether immune function abnormality caused by a mutant human PS1 gene (mhPS1) could modify AD-like pathology, we reconstituted immune systems of AD model mice carrying a mutant human amyloid precursor protein gene (mhAPP; Tg2576 mice) or both mhAPP and mhPS1 genes (PSAPP mice) with allo-geneic bone marrow cells. Here, we report a marked reduction in amyloid-β (Aβ) levels, β-amyloid plaques and brain inflammatory responses in PSAPP mice following strain-matched wild-type PS1 bone marrow reconstitution. These effects occurred with immune switching from pro-inflammatory T helper (Th) 1 to anti-inflammatory Th2 immune responses in the periphery and in the brain, which likely instructed microglia to phagocytose and clear Aβ in an ex vivo assay. Conversely, Tg2576 mice displayed accelerated AD-like pathology when reconstituted with mhPS1 bone marrow. These data show that haematopoietic cells bearing the mhPS1 transgene exacerbate AD-like pathology, suggesting a novel therapeutic strategy for AD based on targeting PS1 in peripheral immune cells. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source

Hermanrud C.,Karolinska Institutet | Ryner M.,Karolinska Institutet | Luft T.,Innsbruck Medical University | Jensen P.E.,Neuroimmunology Laboratory | And 10 more authors.
Journal of Immunological Methods | Year: 2016

Neutralizing anti-drug antibodies (NAbs) against therapeutic interferon beta (IFNβ) in people with multiple sclerosis (MS) are measured with cell-based bioassays. The aim of this study was to redevelop and validate two luciferase reporter-gene bioassays, LUC and iLite, using a cut-point approach to identify NAb positive samples. Such an approach is favored by the pharmaceutical industry and governmental regulatory agencies as it has a clear statistical basis and overcomes the limitations of the current assays based on the Kawade principle. The work was conducted following the latest assay guidelines. The assays were re-developed and validated as part of the "Anti-Biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk" (ABIRISK) consortium and involved a joint collaboration between four academic laboratories and two pharmaceutical companies. The LUC assay was validated at Innsbruck Medical University (LUCIMU) and at Rigshospitalet (LUCRH) Copenhagen, and the iLite assay at Karolinska Institutet, Stockholm. For both assays, the optimal serum sample concentration in relation to sensitivity and recovery was 2.5% (v/v) in assay media. A Shapiro-Wilk test indicated a normal distribution for the majority of runs, allowing a parametric approach for cut-point calculation to be used, where NAb positive samples could be identified with 95% confidence. An analysis of means and variances indicated that a floating cut-point should be used for all assays. The assays demonstrated acceptable sensitivity for being cell-based assays, with a confirmed limit of detection in neat serum of 1519 ng/mL for LUCIMU, 814 ng/mL for LUCRH, and 320 ng/mL for iLite. Use of the validated cut-point assay, in comparison with the previously used Kawade method, identified 14% more NAb positive samples. In conclusion, implementation of the cut-point design resulted in increased sensitivity to detect NAbs. However, the clinical significance of these low positive titers needs to be further evaluated. © 2016 Elsevier B.V.. Source

Nunez M.J.,Neuroimmunology Laboratory | Novio S.,Neuroimmunology Laboratory | Suarez J.A.,Neuroimmunology Laboratory | Balboa J.,Neuroimmunology Laboratory | Freire-Garabal M.,Neuroimmunology Laboratory
Clinical and Vaccine Immunology | Year: 2010

Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source

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