A síndrome de tremor e ataxia associada ao X frágil (FXTAS)

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.FAPESP - Center for the Study of Human Genom

Controle cognitivo associado à indução de irritabilidade: um estudo de RMf usando recordações autobiográficas

OBJECTIVE: Despite the relevance of irritability emotions to the treatment, prognosis and classification of psychiatric disorders, the neurobiological basis of this emotional state has been rarely investigated to date. We assessed the brain circuitry underlying personal script-driven irritability in healthy subjects (n = 11) using functional magnetic resonance imaging. METHOD: Blood oxygen level-dependent signal changes were recorded during auditory presentation of personal scripts of irritability in contrast to scripts of happiness or neutral emotional content. Self-rated emotional measurements and skin conductance recordings were also obtained. Images were acquired using a 1,5T magnetic resonance scanner. Brain activation maps were constructed from individual images, and between-condition differences in the mean power of experimental response were identified by using cluster-wise nonparametric tests. RESULTS: Compared to neutral scripts, increased blood oxygen level-dependent signal during irritability scripts was detected in the left subgenual anterior cingulate cortex, and in the left medial, anterolateral and posterolateral dorsal prefrontal cortex (cluster-wise p-value < 0.05). While the involvement of the subgenual cingulate and dorsal anterolateral prefrontal cortices was unique to the irritability state, increased blood oxygen level-dependent signal in dorsomedial and dorsal posterolateral prefrontal regions were also present during happiness induction. CONCLUSION: Irritability induction is associated with functional changes in a limited set of brain regions previously implicated in the mediation of emotional states. Changes in prefrontal and cingulate areas may be related to effortful cognitive control aspects that gain salience during the emergence of irritability.OBJETIVO: Apesar da relevância de emoções de irritabilidade para o tratamento, prognóstico e classificação dos transtornos psiquiátricos, as bases neurobiológicas deste tipo de estado emocional foram raramente investigadas até hoje. Este estudo avaliou os circuitos cerebrais subjacentes à irritabilidade induzida por scripts pessoais em voluntários saudáveis (n = 11) usando ressonância magnética funcional. MÉTODO: Mudanças no sinal dependente do nível de oxigenação sanguínea (blood-oxygen level dependent signal) foram registradas durante a apresentação por via auditiva de scripts pessoais de irritabilidade em contraste com scripts de felicidade ou de conteúdo emocional neutro. Escores em escalas de autoavaliação emocional e medidas de condutância da pele também foram obtidos. A aquisição de imagens foi realizada em aparelho de ressonância magnética de 1,5 T. Os mapas de ativação cerebral foram construídos a partir das imagens individuais, e as diferenças entre as condições experimentais foram investigadas utilizando testes não-paramétricos baseados em permutações. RESULTADOS: Em comparação com scripts neutros, a apresentação de scripts de irritabilidade levou a aumentos de sinal dependente do nível de oxigenação sanguínea na porção subgenual do giro do cíngulo anterior esquerdo e nas porções medial, ântero-lateral e póstero-lateral do córtex pré-frontal dorsal (cluster-wise p-valor < 0,05). Enquanto o envolvimento do cíngulo anterior subgenual e do córtex pré-frontal dorsal antero-lateral surgiu apenas em associação com o estado de irritabilidade, aumentos do sinal dependente do nível de oxigenação sanguínea nas porções dorso-medial e dorsal póstero-lateral do córtex pré-frontal também estiveram presentes durante indução de felicidade. CONCLUSÃO: Indução de irritabilidade está associada a mudanças de atividade funcional num conjunto restrito de regiões cerebrais previamente implicadas na mediação de estados emocionais. Mudanças na atividade de porções do giro do cíngulo e pré-frontais podem estar relacionadas a esforço de controle cognitivo associado à expressão de emoções de irritabilidade

Oligomerization, Membrane Association, and in Vivo Phosphorylation of Sugarcane UDP-glucose Pyrophosphorylase

Sugarcane is a monocot plant that accumulates sucrose to levels of up to 50% of dry weight in the stalk. The mechanisms that are involved in sucrose accumulation in sugarcane are not well understood, and little is known with regard to factors that control the extent of sucrose storage in the stalks. UDP-glucose pyrophosphorylase (UGPase; EC 2.7.7.9) is an enzyme that produces UDP-glucose, a key precursor for sucrose metabolism and cell wall biosynthesis. The objective of this work was to gain insights into the ScUGPase-1 expression pattern and regulatory mechanisms that control protein activity. ScUGPase-1 expression was negatively correlated with the sucrose content in the internodes during development, and only slight differences in the expression patterns were observed between two cultivars that differ in sucrose content. The intracellular localization of ScUGPase-1 indicated partial membrane association of this soluble protein in both the leaves and internodes. Using a phospho-specific antibody, we observed that ScUGPase-1 was phosphorylated in vivo at the Ser-419 site in the soluble and membrane fractions from the leaves but not from the internodes. The purified recombinant enzyme was kinetically characterized in the direction of UDP-glucose formation, and the enzyme activity was affected by redox modification. Preincubation with H2O2 strongly inhibited this activity, which could be reversed by DTT. Small angle x-ray scattering analysis indicated that the dimer interface is located at the C terminus and provided the first structural model of the dimer of sugarcane UGPase in solution.Fil: Soares, Jose Sergio M.. Universidade Estadual de Campinas. Instituto de Biologia. Departamento de Genética, Evolução e Bioagentes; BrasilFil: Gentile, Agustina. Universidade Estadual de Campinas. Instituto de Biologia. Departamento de Genética, Evolução e Bioagentes; BrasilFil: Scorsato, Valeria. Universidade Estadual de Campinas. Instituto de Química. Laboratório de Biologia Estrutural e Cristalografia; BrasilFil: Lima, Aline da C.. Universidade Estadual de Campinas. Instituto de Química. Laboratório de Biologia Estrutural e Cristalografia; BrasilFil: Kiyota, Eduardo. Universidade Estadual de Campinas. Instituto de Química. Laboratório de Biologia Estrutural e Cristalografia; BrasilFil: Santos, Marcelo Leite Dos . Universidade Federal do Sergipe. Centro de Ciências Exatas e Tecnologia. Núcleo de Química; BrasilFil: Piattoni, Claudia Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Agrobiotecnologia del Litoral; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Huber, Steven C.. University of Illinois at Urbana-Champaign. Department of Agriculture Agricultural Research Service, and Department of Plant Biology; Estados UnidosFil: Aparicio, Ricardo. Universidade Estadual de Campinas. Instituto de Química. Laboratório de Biologia Estrutural e Cristalografia; BrasilFil: Menossi, Marcelo. Universidade Estadual de Campinas. Instituto de Biologia. Departamento de Genética, Evolução e Bioagentes; Brasi

The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice

Background: Multiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). the expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated.Methodology/Principal Findings: Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG(35-55) peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B(1)R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B(1)R antagonist suppressed the production/expression of antigen-specific T(H)1 and T(H)17 cytokines and transcription factors, both in the periphery and in the CNS. in the chronic phase of EAE, the blockade of B(1)R consistently impaired the clinical progression of EAE. Conversely, administration of the B(1)R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. of note, blockade of the B(2)R only showed a moderate impact on all of the studied parameters of EAE progression.Conclusions/Significance: Our results strongly suggest that kinin receptors, mainly the B(1)R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Programa de Apoio aos Nucleos de Excelencia (PRONEX), BrazilFundacaode Apoio a Pesquisa Cientifica Tecnologica do Estado de Santa Catarina (FAPESC), BrazilUniv Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, Florianopolis, SC, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilWeb of Scienc

Effect of an extract of Centella asiatica on the biodistribution of sodium pertechnetate (Na^99mTcO₄) and on the fixation of radioactivity on blood constituents

This study evaluates the effects of an acute treatment with a Centella asiatica (CA) extract on the biodistribution of the radiopharmaceutical Na99mTcO4 and on the fixation of technetium-99m on blood constituents. Wistar rats were treated with CA extract and, 1 hour after, Na99mTcO4 was administered; organs/tissues were withdrawn and weighted. The radioactivity was counted to calculate the percentage of activity per gram (%ATI/g). Also, blood samples were withdrawn, plasma (P), blood cells (BC), insoluble fraction (IF) and soluble fractions of P and BC were isolated and the radioactivity was counted to calculate the percentage of activity (%ATI). Data indicated that the acute treatment with CA extract changed significantly (p99mTcO4 and the fixation of the technetium-99m on blood constituents in an acute treatment

High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population

OBJECTIVE: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). RESULTS: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (

Corpus Callosum Microstructural Changes Correlate with Cognitive Dysfunction in Early Stages of Relapsing-Remitting Multiple Sclerosis: Axial and Radial Diffusivities Approach

The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes

Correlation between hippocampal volumes and proton magnetic resonance spectroscopy of the posterior cingulate gyrus and hippocampi in Alzheimer&apos;s disease

Abstract -Prior studies have reported hippocampal volume loss, decrease in N-Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration in patients with Alzheimer&apos;s disease (AD). The purpose of this study was to evaluate hippocampal volumes of AD patients and their correlation with metabolic changes detected by proton spectroscopy (1H MRS) of hippocampal formations and the posterior cingulate region. Materials and Methods: 22 patients with probable AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were enrolled in the study. Hippocampal volumetric measurements, singlevoxel 1H MRS of the posterior cingulate region and of hippocampal formations were obtained. The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA. Statistical analysis was performed to detect differences and correlations between these parameters in patients and controls. Results: The hippocampal volume of patients and controls did not differ significantly. The results of 1H MRS differed significantly between patients and controls in the hippocampal formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr, mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate region, having a sensitivity of 0.899 and specificity of 0.800. There was no correlation between hippocampal volumes and the results of 1H MRS in patients with AD. Conclusions: The results of 1H MRS differed significantly between patients and controls in hippocampal formations and the posterior cingulate region, with NAA/Cr proving to be the best predictor for AD. No correlation between hippocampal volumes and the results of 1H MRS in patients with AD was observed. Key words: hippocampal volumetry, proton magnetic resonance spectroscopy, Alzheimer&apos;s disease. Correlação entre os volumes hipocampais e a espectroscopia por ressonância magnética do giro do cíngulo posterior e dos hipocampos na doença de Alzheimer Resumo -Estudos anteriores demostraram redução do volume hipocampal, redução da concentração de NAcetilaspartato (NAA) e aumento da concentração de mio-inositol (mI) em pacientes com doença de Alzheimer (DA). O objetivo deste trabalho foi de avaliar os volumes hipocampais de pacientes com DA e correlacioná-los com as alterações metabólicas detectadas pela espectroscopia de próton das formações hipocampais e da região do cíngulo posterior. Material e Métodos: 22 pacientes com provável DA (18 leve, 4 moderada) e 14 controles sem sintomas cognitivos foram incluídos neste estudo . Medidas volumétricas hipocampais, espectroscopia de próton de voxel único das formações hipocampais e da região do cíngulo foram obtidos. As seguintes razões de metabólitos foram avaliadas NAA/Cr, mI/Cr, mI/NAA. Análise estatística foi realizada para detectar as diferenças e correlações entre estes parâmetros nos pacientes e nos controles. Resultados: Os volumes das formações hipocampais dos pacientes e dos controles não foram significativamente diferentes. Os resultados d

Correlation between hippocampal volumes and proton magnetic resonance spectroscopy of the posterior cingulate gyrus and hippocampi in Alzheimer&apos;s disease

Abstract -Prior studies have reported hippocampal volume loss, decrease in N-Acetylaspartate (NAA) concentration and increased myo-inositol (mI) concentration in patients with Alzheimer&apos;s disease (AD). The purpose of this study was to evaluate hippocampal volumes of AD patients and their correlation with metabolic changes detected by proton spectroscopy (1H MRS) of hippocampal formations and the posterior cingulate region. Materials and Methods: 22 patients with probable AD (18 mild, 4 moderate) and 14 elderly controls without cognitive symptoms, were enrolled in the study. Hippocampal volumetric measurements, singlevoxel 1H MRS of the posterior cingulate region and of hippocampal formations were obtained. The following metabolite ratios were evaluated: NAA/Cr, mI/Cr, mI/NAA. Statistical analysis was performed to detect differences and correlations between these parameters in patients and controls. Results: The hippocampal volume of patients and controls did not differ significantly. The results of 1H MRS differed significantly between patients and controls in the hippocampal formations (mI/Cr, mI/NAA) and posterior cingulate region (NAA/Cr, mI/Cr, mI/NAA). The best predictor of AD diagnosis was NAA/Cr in the posterior cingulate region, having a sensitivity of 0.899 and specificity of 0.800. There was no correlation between hippocampal volumes and the results of 1H MRS in patients with AD. Conclusions: The results of 1H MRS differed significantly between patients and controls in hippocampal formations and the posterior cingulate region, with NAA/Cr proving to be the best predictor for AD. No correlation between hippocampal volumes and the results of 1H MRS in patients with AD was observed. Key words: hippocampal volumetry, proton magnetic resonance spectroscopy, Alzheimer&apos;s disease. Correlação entre os volumes hipocampais e a espectroscopia por ressonância magnética do giro do cíngulo posterior e dos hipocampos na doença de Alzheimer Resumo -Estudos anteriores demostraram redução do volume hipocampal, redução da concentração de NAcetilaspartato (NAA) e aumento da concentração de mio-inositol (mI) em pacientes com doença de Alzheimer (DA). O objetivo deste trabalho foi de avaliar os volumes hipocampais de pacientes com DA e correlacioná-los com as alterações metabólicas detectadas pela espectroscopia de próton das formações hipocampais e da região do cíngulo posterior. Material e Métodos: 22 pacientes com provável DA (18 leve, 4 moderada) e 14 controles sem sintomas cognitivos foram incluídos neste estudo . Medidas volumétricas hipocampais, espectroscopia de próton de voxel único das formações hipocampais e da região do cíngulo foram obtidos. As seguintes razões de metabólitos foram avaliadas NAA/Cr, mI/Cr, mI/NAA. Análise estatística foi realizada para detectar as diferenças e correlações entre estes parâmetros nos pacientes e nos controles. Resultados: Os volumes das formações hipocampais dos pacientes e dos controles não foram significativamente diferentes. Os resultados d

Preliminary identification of the bioremediation limiting factors of a clay bearing soil contaminated with crude oil

Bioremediation is an attractive alternative to treat soils contaminated with petroleum hydrocarbons. However, the effectiveness of biodegradation process can be limited by both contaminant characteristics and its bioavailability in soil. This work aims at establishing a preliminary procedure to identify the main factor (hydrocarbon recalcitrance or its bioavailability) that impairs the biodegradation, possibly resulting in low remediation efficiencies. Tests in soil microcosms were carried out applying biostimulation and bioaugmentation techniques. Similar experiments were conducted using liquid medium containing crude oil and microorganisms, both of them extracted from a weathered contaminated soil sample, nutrients and microbial inoculum constituted of Rhodoturula glutinis and Nocardia nova. After 30 days, highest microcosms biodegradation levels (98.8%) were obtained with bioaugmentation in liquid medium, pointing out that the main problem of petroleum hydrocarbon utilization by microorganisms was associated to its availability and not only to the intrinsic recalcitrancy of remaining pollutants