149 research outputs found

    Investigation of Oligoclonal IgG Bands in Tear Fluid of Multiple Sclerosis Patients

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    Background: Oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF) represent a typical marker for inflammation in multiple sclerosis (MS) patients and have a predictive and diagnostic value in patients with a first suspected demyelinating event. The detection in tears remains controversial but some reports suggested a replacement of CSF analysis by OCB detection in tears. We aimed to investigate the value of OCB detection in tears systematically in patients with MS.Methods: Tears of 59 patients with suspected or diagnosed MS were collected with Schirmer filter paper strips. Tear IgG was purified by affinity chromatography with protein G. After isoelectric focusing in polyacrylamide gels OCB detection was performed with direct silver staining. Paired triplets of CSF, serum, and tears were analyzed. For comparison purposes we additionally used other tear collection methods (flush procedure and plastic capillary tubes) or detection techniques (Immunoblotting). Clinical and paraclinical parameters are provided.Results: IgG collection in tears was most reliable by using Schirmer strips. Thirteen patients had to be excluded due to insufficient sample material. Tear specific proteins that interfered with OCB detection were successfully eliminated by IgG purification. The concordance of OCB in tears and CSF of all investigated MS patients was 39% with a high rate of only marginal pattern in tears. Five patients demonstrated restricted bands in tears, neither detectable in CSF nor serum. Occurrence of OCB in tears was significantly associated with pathological visual evoked potentials (P = 0.0094) and a history of optic neuritis (P = 0.0258).Conclusion: Due to the limited concordance, high rate of samples with insufficient material, and the unknown origin of tear IgG we cannot recommend that tear OCB detection may replace CSF OCB detection in MS patients. The detection of unique OCB in tears might offer new insights in ophthalmological diseases

    Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

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    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

    A β-Lactam Antibiotic Dampens Excitotoxic Inflammatory CNS Damage in a Mouse Model of Multiple Sclerosis

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    In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), impairment of glial “Excitatory Amino Acid Transporters” (EAATs) together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS). In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a β-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in “Myelin Oligodendrocyte Glycoprotein” (MOG)-induced EAE. Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens. However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2. Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course. This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter. Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFγ and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs) e.g. dendritic cells (DCs) and reduced T cell migration into the CNS in vivo. Taken together, we demonstrate, that a β-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation. The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis

    White matter correlates of complex processing speed performance in relapsing-remitting multiple sclerosis

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    Background: Natalizumab (NTZ) exerts a positive impact on cognitive functions in Relapsing Multiple Sclerosis (RRMS). Little is known about the effect of Fingolimod (FIN) on these functions. Objectives: to compare the effect on cognitive functions of 1-year treatment with FIN or NTZ. Methods: All consecutive RRMS scheduled for treatment with NTZ or FIN underwent neuropsychological evaluations using the Brief Repeatable Battery, Stroop Test, Fatigue Severity Scale (FSS) and Beck Depression Inventory (BDI) at baseline and every 12 months. A test was considered failed if the corresponding z-score was 2 standard deviation (SD) below the mean Italian normative values. The Cognitive Impairment Index (CII) as a measure of global cognitive function was calculated for each patient. Patients were propensity score (PS)-matched on a 1-to-1 basis at the time of treatment start using the following covariates: sex, age, prior treatment exposure, relapses prior the treatment, school education, and BDI score. The relapse risk during the treatment was estimated through a Poisson regression model. A generalized linear mixed model for repeated measures with an autoregressive variance-covariance structure was applied to evaluate changes in CII, the mean number of cognitive tests failed and FSS score at 1 year of treatment. Results: the effect of treatment on cognitive functions was evaluated in 62 matched RRMS patients receiving NTZ(n=31) or FIN(n=31). The relapse incidence was not significant different between the treatments (FIN vs NTZ: Incidence rate ratio=0.71, p=0.6). The mean±SD number of cognitive tests failed was significantly reduced only in FIN treated patients (2.8±2.2 vs 1.7±1.8, p=0.0014). The CII significantly improved in both groups (NAT 18.5±6.1 vs 14.5±6.1, p=0.0075; FIN 14.0±7.3 vs 11.5±7.5, p< 0.0001), but there was not a significant interaction between group X time. The FSS was unchanged in both groups. Conclusions: Our results indicates, for the first time, that both NAT and FIN treatments significantly ameliorate cognitive functions in RRMS. Moreover, the effect on the number of tests failed suggest that FIN could have a greater impact on cognition than NTZ. The effect on cognition of these two drugs goes in parallel with the reduction of the relapse rate. This latter finding support the hypothesis that in the short-term, NTZ and FIN, exert a positive impact on cognition likely by means of their anti-inflammatory properties

    Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

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    9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe
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