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Altas E.,Ege University | Gurhan I.D.,Ege University | Urkmez A.S.,Ege University | Urkmez A.S.,Center for Brain Research
10th International Workshop on Biomedical Engineering, BioEng 2011 | Year: 2011

Co-Cr and Ni-Cr based dental metal alloys are often preferred in the restoration processes inside the mouth for repairing the esthetic and functional irregularities of teeth. In this study, the cytotoxic and genotoxic effects of the possible man-made errors in the production of the dental crowns and bridges from the mentioned casting alloys in-vitro were investigated applying the test protocols according to TS EN ISO 10993 standards. As the possible man-made errors in this production, the duration of oxy-acetylene welding flame applied during the melting stage of the process and polishing time during the polishing process are determined. Their 9 different combinations are the investigated parameters of the study. Results showed that the welding flame induces toxicity in both of the alloys. In the cytotoxicity tests, as the duration of oxy-acetylene welding flame exposure increase, the negative effects on viability and morphological changes of the cells are noticed. Also increasing polishing time in the production process induces cytotoxicity and genotoxicity of these dental alloys. © 2011 IEEE.


Mollersen L.,University of Oslo | Rowe A.D.,University of Oslo | Illuzzi J.L.,U.S. National Institute on Aging | Hildrestrand G.A.,University of Oslo | And 6 more authors.
Human Molecular Genetics | Year: 2012

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by trinucleotide repeat (TNR) expansions. We show here that somatic TNR expansions are significantly reduced in several organs of R6/1 mice lacking exon 2 of Nei-like 1 (Neil1) (R6/1/Neil1-/-), when compared with R6/1/Neil1+/+ mice. Somatic TNR expansion is measured by two different methods, namely mean repeat change and instability index. Reduced somatic expansions are more pronounced in male R6/1/Neil1-/- mice, although expansions are also significantly reduced in brain regions of female R6/1/Neil1-/- mice. In addition, we show that the lack of functional Neil1 significantly reduces germline expansion in R6/1 male mice. In vitro, purified human NEIL1 protein binds and excises 5-hydroxycytosine in duplex DNA more efficiently than in hairpin substrates. NEIL1 excision of cytosine-derived oxidative lesions could therefore be involved in initiating the process of TNR expansion, although other DNA modifications might also contribute. Altogether, these results imply that Neil1 contributes to germline and somatic HD CAG repeat expansion. © The Author 2012. Published by Oxford University Press. All rights reserved.


Castelo-Branco G.,Karolinska Institutet | Stridh P.,Karolinska Institutet | Guerreiro-Cacais A.O.,Karolinska Institutet | Adzemovic M.Z.,Karolinska Institutet | And 8 more authors.
Neurobiology of disease | Year: 2014

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS) in young adults. Chronic treatments with histone deacetylase inhibitors (HDACis) have been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by targeting immune responses. We have recently shown that the HDAC inhibition/knockdown in the presence of thyroid hormone (T3) can also promote oligodendrocyte (OL) differentiation and expression of myelin genes in neural stem cells (NSCs) and oligodendrocyte precursors (OPCs). In this study, we found that treatment with an HDACi, valproic acid (VPA), and T3, alone or in combination, directly affects encephalitogenic CD4+ T cells. VPA, but not T3, compromised their proliferation, while both molecules reduced the frequency of IL-17-producing cells. Transfer of T3, VPA and VPA/T3 treated encephalitogenic CD4+ T cells into naïve rats induced less severe EAE, indicating that the effects of these molecules are persistent and do not require their maintenance after the initial stimuli. Thus, we investigated the effect of acute treatment with VPA and l-thyroxine (T4), a precursor of T3, on myelin oligodendrocyte glycoprotein-induced EAE in Dark Agouti rats, a close mimic of MS. We found that a brief treatment after disease onset led to sustained amelioration of EAE and prevention of inflammatory demyelination in the CNS accompanied with a higher expression of myelin-related genes in the brain. Furthermore, the treatment modulated immune responses, reduced the number of CD4+ T cells and affected the Th1 differentiation program in the brain. Our data indicate that an acute treatment with VPA and T4 after the onset of EAE can produce persistent clinically relevant therapeutic effects by limiting the pathogenic immune reactions while promoting myelin gene expression. Copyright © 2014. Published by Elsevier Inc.


Pinzon N.E.,VU University Amsterdam | Stroo E.,VU University Amsterdam | Stroo E.,University of Groningen | 'T Hart B.A.,Biomedical Primate Research Center | And 5 more authors.
PLoS ONE | Year: 2014

Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2) in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation. © 2014 Espitia Pinzon et al.


Bauer J.,Center for Brain Research | Vezzani A.,Mario Negri Institute for Pharmacological Research | Bien C.G.,Epilepsy Center Bethel
Brain Pathology | Year: 2012

Seizures are a prominent clinical feature of encephalitis. Recent data suggest the adaptive as well as innate immune system to be involved directly in the pathomechanism of epileptogenesis. Cytotoxic T-cells and antibody-mediated complement activation are major components of the adaptive immune system, which can induce neurodegeneration, thereby probably contributing to epileptic encephalitis. The innate immune system operates via interleukin-1 and toll-like receptor-associated mechanisms and was shown to play a direct role in epileptogenesis. Here, we review neuropathology hallmarks of various encephalitis conditions such as Rasmussen encephalitis (RE) but also introduce the more recently discovered antibody-associated voltage-gated potassium channel complex (VGKC), N-methyl-D-aspartate receptor (NMDAR) or glutamic acid decarboxylase (GAD) 65 encephalitides. Neuropathological investigations are used to determine specific cellular components and molecular mechanisms used by the immune system to provoke neurodegeneration and to promote epileptogenesis. Based on recent findings, we propose concepts for the stratification of epileptic encephalitis. Knowledge of the role of the innate immunity has already translated into clinical treatment strategies and may help to discover novel drug targets for these epileptic disorders. © 2012 The Authors; © 2012 International Society of Neuropathology.

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