Poudarowe zaburzenia poznawcze

Otępienie naczyniopochodne (VaD, vascular dementia) jest, obok choroby Alzheimera (AD, Alzheimer’s disease) i otępienia z ciałami Lewy’ego (DLB, dementia with Lewy bodies), najczęściej występującą postacią otępienia. Naczyniopochodne zaburzenia poznawcze (VCI, vascular cognitive impairment) dotyczą wszystkich postaci zaburzeń poznawczych, od łagodnych do ciężkich, które towarzyszą lub przypuszczalnie są spowodowane naczyniowymi chorobami mózgu. Tak rozumiane VCI obejmują: otępienie naczyniopochodne, naczyniopochodne zaburzenia poznawcze bez otępienia (VCIND, vascular cognitive impairment without dementia) oraz naczyniopochodne łagodne zaburzenia poznawcze (VMCI, vascular mild cognitive impairment). Naczyniopochodne zaburzenia poznawcze są następstwem udaru mózgu, mnogich zawałów korowych i podkorowych mózgu, choroby małych naczyń krwionośnych mózgu przebiegającej z uszkodzeniem istoty białej, stanu zatokowego lub krwotoku mózgowego. Otępienie poudarowe zdarza się u 16–30% chorych w okresie do 3 miesięcy od wystąpienia udaru. U części chorych wczesne poudarowe zaburzenia poznawcze przybierają korzystny przebieg — stają się samoistnie całkowicie lub częściowo odwracalne. Udowodniono objawową skuteczność inhibitorów acetylocholinesterazy w VaD. Skuteczną metodą zapobiegania VaD jest prewencja pierwotna, polegająca na leczeniu lub unikaniu modyfikowalnych czynników ryzyka: nadciśnienia tętniczego, cukrzycy, dyslipidemii, palenia tytoniu, braku aktywność fizycznej oraz niedoboru witaminy B12 i kwasu foliowego. Należy jednak pamiętać, że prewencję VaD należy rozpocząć odpowiednio wcześnie

An Influence of Immunomodulation on Th1 and Th2 Immune Response in Endometriosis in an Animal Model

Aim.To assess the role of the Th1 and Th2 cellular response in the etiology of endometriosis observed in a rat model, with the use of the RESAN immunomodulator.Materials and Methods.A comparative analysis of cytokines in blood serum typical of Th1 (TNF-αand INF-γ) and Th2 (IL-4, IL-6, IL-10) cell response in groups of rats, in which RESAN preparation was used as prophylaxis (Gr. I) or treatment (Gr. II) of endometriosis.Results.The results indicated an increase in the level of cytokines in blood serum typical of Th2 cell response by comparing the second and third stages of the experiment in the second group of rats and a decrease in IL-4 and IL-10 between III and IV stages. There was a significant difference in cytokine levels during the third stage of the experiment by comparing I and II groups of rats. In the III group of rats, levels of IL-10 significantly increased between the II and III stages of the experiment.Conclusion.RESAN preparation shows Th2 cell response, inhibiting the development of endometriosis in a rat model. Due to successful prophylactic action, one may speculate that RESAN vaccine may be effective as a complementary treatment after surgical excision.</jats:p

Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD

Creation of an open-access, mutation-defined fibroblast resource for neurological disease research.

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis