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1.
Food Chem ; 448: 139153, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569410

RESUMO

Salivary proteins precipitation by interaction with polyphenols is the major mechanism for astringency. However, alternative mechanisms seem involved in the perception of different subqualities of astringency. In this study, adsorption of four astringent agents to in vitro oral models and their sensory properties were assessed. Overall, green tea infusion and tannic acid have shown a higher adsorption potential for models with oral cells and absence of saliva. Alum and grape seed extract presented higher adsorption in models with presence of oral cells and saliva. Multiple factor analysis suggested that adsorption may represent important mechanisms to elicit the astringency of alum. Models including saliva, were closely associated with overall astringency and aggressive subquality. Models with cells and absent saliva were closely associated with greenness, suggesting a taste receptor mechanism involvement in the perception. For the first time a correlation between an oral-cell based assay and astringency sensory perception was shown.

2.
J Peripher Nerv Syst ; 28(1): 119-124, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36721348

RESUMO

It was argued that researchers and clinicians are not able to make judgments between most categories of the original Medical Research Council (MRC) scale and that a modified short version would reach higher agreement levels. We aimed to assess the inter-rater reliability for both the original and the Rasch-modified MRC scoring criteria of Manual Muscle Strength tests (MMSt) in patients with neuromuscular diseases. Two MRC scoring criteria were used to score muscle strength using MMSt in 40 muscle groups of the upper and lower limbs in patients with neuromuscular disorders. Three investigators performed the evaluations; the order of the MMSt and the use of the scales were performed according to the preferences of the investigators. The agreement coefficient (Gwet's AC2 ) was used to compute the reliability. Sixty patients (mean age of 39.3 years ± 15.2) with neuromuscular diseases were included. The mean AC2 for the muscle groups of the upper limbs ranged from 0.82 to 0.96 using the modified MRC scale and from 0.86 to 0.96 using the original MRC scale. The AC2 for the lower limb muscle groups ranged from 0.80 to 0.91 (modified MRC scale) and from 0.87 to 0.93 (original MRC scale). These values might be interpreted as "almost perfect agreement" with no significant differences between the scales. The results indicate that both MRC scoring criteria have significant reliability among trained observers. Moreover, the Rasch-modified MRC scale is as reliable as the original MRC scale and can be used in future clinical studies.


Assuntos
Pesquisa Biomédica , Doenças Neuromusculares , Humanos , Adulto , Reprodutibilidade dos Testes , Músculo Esquelético , Força Muscular/fisiologia , Doenças Neuromusculares/diagnóstico
3.
J Agric Food Chem ; 71(4): 2070-2081, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36652684

RESUMO

It is well known that repeated exposure to phenolic compounds (PCs) raises astringency perception. However, the link between this increase and the oral cavity's interactions with salivary proteins (SPs) and other oral constituents is unknown. To delve deeper into this connection, a flavonoid-rich green tea extract was tested in a series of exposures to two oral cell-based models using a tongue cell line (HSC3) and a buccal mucosa cell line (TR146). Serial exposures show cumulative PC binding to all oral models at all concentrations of the green tea extract; however, the contribution for the first and second exposures varies. The tongue mucosal pellicle (HSC3-Mu-SP) may contribute more to first-stage astringency (retaining 0.15 ± 0.01 mg mL-1 PCs at the first exposure), whereas the buccal mucosal pellicle (TR146-Mu-SP) retained significantly less (0.08 ± 0.02 mg mL-1). Additionally, increased salivary volume (SV+), which simulates the stimulation of salivary flow brought by a food stimulus, significantly enhances PC binding, particularly for TR146 cells: TR46-Mu-SP_SV+ bound significantly higher total PC concentration (0.17 ± 0.02 mg mL-1) than the model without increased salivary volume TR146-Mu-SP_SV- (0.09 ± 0.03 mg mL-1). This could be associated with a higher contribution of these oral cells for astringency perception during repeated exposures. Furthermore, PCs adsorbed in the first exposure to cell monolayer models (+TR146 and +HSC3) change the profile of PCs bound to these models in the second exposure. Regarding the structure binding activity, PCs with a total higher number of hydroxyl groups were more bound by the models containing SP. Regarding the SP, basic proline-rich proteins (bPRPs) may be involved in the increased perception of astringency upon repeated exposures. The extent of bPRP precipitation by PCs in mucosal pellicle models for both cell lines (HSC3 and TR146) in the second exposure (76 ± 13 and 83 ± 6%, respectively) was significantly higher than in the first one (25 ± 14 and 5 ± 6%, respectively).


Assuntos
Adstringentes , Flavonoides , Aspergillus fumigatus/metabolismo , Adstringentes/química , Azóis , Farmacorresistência Fúngica , Flavonoides/metabolismo , Proteínas Fúngicas/metabolismo , Fenóis/metabolismo , Saliva/química , Proteínas e Peptídeos Salivares/metabolismo , Chá/metabolismo , Boca
4.
Food Chem ; 375: 131642, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34838404

RESUMO

Astringency is a tactile sensation of puckering, tightening and dryness in the oral cavity, commonly induced by polyphenols. In this study, the interaction of two phenolic compound mixtures, one rich in gallotannins and the other in flavonols, with two oral models (tongue (HSC3) or buccal mucosa (TR146) was evaluated. Results provided evidence that gallotannins and flavonols seem to bind in a different way to the different oral constituents and models used. Gallotannins seems to bind more to the tongue than to the buccal mucosa cell line, but this difference is overcome by the presence of salivary proteins. Conversely, for the flavonol mixture, the presence of salivary proteins seems to restrain the interaction with oral cell lines. Structure-binding activity relationships were evidenced within each mixture: for gallotannins, interactions seem to increase along with the galloylation degree while for flavonol it was observed that increasing numbers of glucose residues decreased the binding activity.


Assuntos
Adstringentes , Proteínas e Peptídeos Salivares , Flavonóis , Boca , Fenóis
5.
Epilepsy Behav ; 112: 107469, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33181902

RESUMO

The most common form of genetic generalized epilepsy (GGE) is juvenile myoclonic epilepsy (JME), which accounts for 5 to 10% of all epilepsy cases. The gene EFHC1 has been implicated as a putative cause of JME. However, it remains debatable whether testing for EFHC1 mutations should be included in the diagnostic epilepsy gene panels. To investigate the clinical utility of EFHC1 testing, we studied 125 individuals: 100 with JME and 25 with other GGEs. We amplified and sequenced all EFHC1 coding exons. Then, we predicted the pathogenicity or benign impact of the variants using the analyses proposed by the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP). Mutation screening revealed 11 missense variants in 44 probands with JME (44%) and one of the seven individuals with generalized tonic-clonic seizures on awakening (14%). Six of the 11 variants (54%) were classified as 'benign,' and the remaining variants were considered variants of uncertain significance (VUS). There is currently a limitation to test for genes that predispose an individual to complex, nonmonogenic phenotypes. Thus, we show suggestive evidence that EFHC1 testing lacks a scientific foundation based on the disputed nature of the gene-disease relationship and should be currently limited to research purposes.


Assuntos
Epilepsia Generalizada , Epilepsia Mioclônica Juvenil , Proteínas de Ligação ao Cálcio/genética , Epilepsia Generalizada/genética , Humanos , Epilepsia Mioclônica Juvenil/genética , Linhagem , Fenótipo
6.
J Agric Food Chem ; 68(47): 13824-13832, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33170702

RESUMO

Procyanidins are widely associated with astringency perception and promptly interact/precipitate salivary proteins (SPs). In this work, the SP profile of 17 volunteers was monitored for 1 year, focusing on the SP families most related to astringency [aPRPs (acidic proline-rich proteins), bPRPs (basic proline-rich proteins), gPRPs (glycosylated proline-rich proteins), cystatins, P-B peptide, and statherin]. Although the total SP content remained constant, bPRPs showed high variability. Saliva from 5 volunteers was selected, each individual's saliva presenting a prominence in one of the referred SP families; each was used to interact with grape seed procyanidin oligomeric fraction. Independent of the prominences, a total depletion in statherin and P-B peptide was observed. These subjects performed a sensory assay and the limit of detection for astringency was determined. Overall, the specificity of SP toward procyanidins seemed to be more important in the interactions than the total SP content. The highest reactivity toward SPs was observed for epicatechin gallate, procyanidin dimers B7, B2g, and trimer C1.


Assuntos
Biflavonoides , Proantocianidinas , Catequina , Humanos , Saliva , Proteínas e Peptídeos Salivares
7.
Sci Rep ; 10(1): 12638, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724226

RESUMO

Phenolic compounds (PC) are linked to astringency sensation. Astringency studies typically use simple models, with pure PC and/or proteins, far from what is likely to occur in the oral cavity. Different oral models have been developed here, comprising different oral epithelia (buccal mucosa (TR146) and tongue (HSC-3)) and other main oral constituents (human saliva and mucosal pellicle). These models, were used to study the interaction with two PC extracts, one rich in flavanols (a green tea extract) and one rich in anthocyanins (a red wine extract). It was observed that within a family of PC, the PC seem to have a similar binding to both TR146 and HSC-3 cell lines. When the oral constituents occur altogether, flavanols showed a higher interaction, driven by the salivary proteins. Conversely, anthocyanins showed a lower interaction when the oral constituents occur altogether, having a higher interaction only with oral cells. Epigallocatechin gallate, epicatechin gallate, epigallocatechin-3-O(3-O-methyl) gallate were the flavanols with the highest interaction. For the studied anthocyanins (delphinidin-3-glucoside, peonidin-3-glucoside, petunidin-3-glucoside and malvidin-3-glucoside), there was not a marked difference on their interaction ability. Overall, the results support that the different oral constituents can have a different function at different phases of food (PC) intake. These differences can be related to the perception of different astringency sub-qualities.


Assuntos
Antocianinas/metabolismo , Flavonóis/metabolismo , Mucosa Bucal/metabolismo , Extratos Vegetais/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Chá/química , Língua/metabolismo , Vinho/análise , Adulto , Células Cultivadas , Feminino , Humanos , Técnicas In Vitro , Masculino , Saliva/metabolismo , Adulto Jovem
8.
Molecules ; 25(11)2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32498458

RESUMO

Astringency and bitterness are organoleptic properties widely linked to tannin compounds. Due to their significance to food chemistry, the food industry, and to human nutrition and health, these tannins' taste properties have been a line of worldwide research. In recent years, significant advances have been made in understanding the molecular perception of astringency pointing to the contribution of different oral key players. Regarding bitterness, several polyphenols have been identified has new agonists of these receptors. This review summarizes the last data about the knowledge of these taste properties perceived by tannins. Ultimately, tannins' astringency and bitterness are hand-in-hand taste properties, and future studies should be adapted to understand how the proper perception of one taste could affect the perception of the other one.


Assuntos
Adstringentes/análise , Taninos/análise , Paladar , Análise de Alimentos , Indústria Alimentícia , Humanos , Polifenóis/química
9.
Carbohydr Polym ; 236: 116044, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172858

RESUMO

In this study, water and chelator-soluble pectic polysaccharide fractions were obtained from white grape skins, aiming to study their impact on the interaction between low polymerized grape seed procyanidins and salivary proteins. Water and chelator-soluble polysaccharide fractions were composed by uronic acids and neutral sugars, mainly arabinose and galactose, with water polysaccharide fraction showing a higher amount of branched pectic polysaccharides. Both polysaccharide fractions were able to mitigate salivary protein-procyanidin interactions, by a competition mechanism, resulting in a decrease of the amount of precipitated protein. Water polysaccharide fraction was the most effective in inhibiting salivary protein precipitation, especially for acidic proline-rich proteins, due to the higher affinity to interact with procyanidins (KA = 22222 M-1 and KA = 365 M-1 for water and chelator polysaccharides, respectively). The interaction between polysaccharides and procyanidins showed to be mainly governed by hydrophobic effect.


Assuntos
Biflavonoides/metabolismo , Catequina/metabolismo , Pectinas/química , Proantocianidinas/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Vitis/química , Biflavonoides/análise , Biflavonoides/isolamento & purificação , Catequina/análise , Catequina/isolamento & purificação , Frutas/química , Humanos , Pectinas/análise , Pectinas/isolamento & purificação , Proantocianidinas/análise , Proantocianidinas/isolamento & purificação , Ligação Proteica/efeitos dos fármacos
10.
J Agric Food Chem ; 67(46): 12833-12843, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657214

RESUMO

Some polyphenols have unpleasant taste properties such as astringency, which could interfere with consumers' choices. The knowledge on astringency mechanisms points that astringency is a complex phenomenon probably related to more than one physical-chemical mechanism. Thus, this work aims to develop a new and more realistic cell-based model containing human saliva, mucosa pellicle, and an oral cell line (HSC-3) to understand the oral molecular events that could contribute to the overall astringency perception. This model was then used to study the interactions with a food procyanidin fraction (PF) by HPLC. In general, the results revealed higher interaction (synergism) for the model with all the referred oral constituents (mucosa pellicle, salivary proteins, and HSC-3 cell line, HSCMuSp) when compared to the interaction with individual constituents, the PF + cells or PF + saliva. Regarding the procyanidins, a significant interaction was observed for the procyanidin monomer EcG, procyanidin dimers B7 and B2G, and trimer C1.


Assuntos
Boca/metabolismo , Polifenóis/metabolismo , Linhagem Celular , Humanos , Modelos Biológicos , Polifenóis/análise , Proantocianidinas/análise , Proantocianidinas/metabolismo , Saliva/metabolismo , Paladar
11.
J Agric Food Chem ; 67(34): 9579-9590, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31381329

RESUMO

The first contact of tannins with the human body occurs in the mouth, where some of these tannins are known to interact with salivary proteins, in particular with proline-rich proteins (PRPs). These interactions are important at a sensory level, especially for astringency development, but could also affect the biological activities of the tannins. This study gathers information on the relative affinity of the interaction, complex stoichiometry, and tannin molecular epitopes of binding for the interactions between the families of PRPs (bPRPs, gPRPs, and aPRPs) and three representative ellagitannins (castalagin, vescalagin, and punicalagin). These interactions were studied by saturation-tranfer difference NMR and microcalorimetry. The effect of the PRP-ellagitannin interaction on their antioxidant ability was also assessed by ferric reduction antioxidant power (FRAP) assays. The results support a significant interaction between the studied tannins and PRPs with binding affinities in the micromolar range. Punicalagin was always the ellagitannin with higher affinity. aPRPs were the salivary PRPs with higher affinity. Moreover, it was observed that when ellagitannins are present in low concentrations (5-50 µM), as occurs in food, the antioxidant ability of these tannins when complexed with salivary PRPs could be significantly impaired.


Assuntos
Taninos Hidrolisáveis/química , Proteínas Salivares Ricas em Prolina/química , Antioxidantes/química , Antioxidantes/metabolismo , Adstringentes/química , Adstringentes/metabolismo , Humanos , Taninos Hidrolisáveis/metabolismo , Cinética , Ligação Proteica , Saliva/química , Saliva/metabolismo , Proteínas Salivares Ricas em Prolina/metabolismo , Paladar
12.
Pharmacogenomics J ; 19(1): 72-82, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30131588

RESUMO

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.


Assuntos
Galanina/genética , Esclerose Múltipla/genética , Receptor Tipo 2 de Galanina/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Estudos de Casos e Controles , Linhagem Celular , Feminino , Células HEK293 , Humanos , Fosforilação/genética , Polimorfismo de Nucleotídeo Único/genética , Transdução de Sinais/genética , Adulto Jovem
13.
Epilepsy Behav ; 86: 124-130, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30017836

RESUMO

Executive deficits and impulsiveness are extensively reported in juvenile myoclonic epilepsy (JME). Previous literature suggests that intelligence may mediate these deficits. In this study, we evaluated and compared the performance of adults with JME with high and low intelligence quotient (IQ) and controls on tasks for executive function (EF) and impulsive traits. We investigated the neuropsychological performance of 53 adults with JME and below average IQ (57% women; 26.9 [±7.88] years; mean IQ: 89.8 [±5.1]), 26 adults with JME and average or above average IQ (53.8% women; 28.2 [±9.33] years; mean IQ: 110.7 [±8.3]), 38 controls with below average IQ (55% women; 28.4 [±8.4] years; mean IQ: 90.1 [±5.8]), and 31 controls with average or above average IQ (61.3% women; 32.20 [±11.3] years; mean IQ: 111.6 [±10.5]) with a comprehensive battery of neuropsychological tests that measure executive/attentional function. Impulsive traits were assessed using the Cloninger et al.'s Temperament and Character Inventory (novelty seeking (NS) domain). The group with JME with higher IQ presented worse performance compared with controls with higher IQ on Controlled Oral Word Association (COWA) and Wisconsin Card Sorting Test (WCST) (errors). This group showed worse performance than controls with lower IQ on Stroop Color-Word Test (SCT) 1, Trail Making (TM) A, COWA, and WCST (errors). Patients with lower IQ showed worse performance than controls with higher IQ on Digit Span Forward (DSF), Digit Span Backward (DSB), SCT1, SCT2, SCT3, TM A, COWA, and WCST (errors and failure to maintain set). Patients with lower IQ showed worse performance than controls with lower IQ on DSF, DSB, SCT1, SCT2, SCT3, TM A, TM B, COWA, and WCST (errors and failure to maintain set). Patients from groups with low and high IQ showed higher scores than controls with higher and lower IQ on impulsivity for NS1 and NS2 (except for patients with higher IQ versus controls with lower IQ). Adults with JME and higher IQ show less evidence of EF deficits compared with those with JME and below average IQ, suggesting that a higher degree of intellectual efficiency may act as a compensatory mechanism. However, it does not minimize some aspects of impulsive traits. Patients with JME and higher cognitive reserve may create strategies to dodge their cognitive obstacles. In this context, intelligence may protect and, at the same time, "mask" impairments that could be detected earlier.


Assuntos
Inteligência , Epilepsia Mioclônica Juvenil/psicologia , Adolescente , Adulto , Atenção , Cognição , Função Executiva , Feminino , Voluntários Saudáveis , Humanos , Comportamento Impulsivo , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Teste de Stroop , Teste de Sequência Alfanumérica , Testes de Associação de Palavras , Adulto Jovem
14.
J Clin Densitom ; 21(1): 48-53, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28302355

RESUMO

Reduction of bone mineral density and the risk of osteopenia have been reported to occur in phenylketonuria (PKU) patients. This study aimed to evaluate the short-term effects of calcium supplementation in phenylketonuric children and adolescents. The study included 18 patients with PKU aged 5-18 yr (61% male) under clinical and nutritional treatment. Evaluation of food intake, anthropometry, and biochemical and phalangeal quantitative ultrasound were performed before (phase 1) and after (phase 2) calcium supplementation (1000 mg/d) for 34 d. Statistical analysis was performed using t test for paired samples, Wilcoxon's test, and McNemar's test (p <0.05). There was an inadequate intake of phosphorus and vitamin D, the same occurring with serum concentrations of these nutrients. About 50% of the patients had an accumulation of adipose tissue measures, with a negative correlation between Z-score, body mass index, and phalangeal quantitative ultrasound (amplitude-dependent speed of sound [AD-SoS]). There was a significant difference in urinary phosphorus excretion with higher values before supplementation. Comparison of the two phases revealed significantly higher AD-SoS values after the supplementation (p = 0.017). The reduction in phosphorus excretion associated with increased AD-SoS between the two phases suggested increased bone formation, and showed no negative effects in relation to short-term calcium supplementation in children and in adolescents with PKU.


Assuntos
Cálcio/sangue , Cálcio/uso terapêutico , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/metabolismo , Fósforo/urina , Adiposidade , Adolescente , Índice de Massa Corporal , Densidade Óssea , Cálcio/administração & dosagem , Cálcio/urina , Criança , Pré-Escolar , Dieta , Suplementos Nutricionais , Feminino , Falanges dos Dedos da Mão/diagnóstico por imagem , Humanos , Masculino , Fenilalanina/sangue , Fenilcetonúrias/complicações , Fósforo/sangue , Fatores de Tempo , Ultrassonografia , Vitamina D/sangue
15.
NeuroRehabilitation ; 39(2): 301-4, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27372365

RESUMO

BACKGROUND: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). OBJECTIVE: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. METHODS: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. RESULTS: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. CONCLUSION: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.


Assuntos
4-Aminopiridina/uso terapêutico , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/tratamento farmacológico , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológico , Bloqueadores dos Canais de Potássio/uso terapêutico , 4-Aminopiridina/farmacologia , Adulto , Idoso , Feminino , Transtornos Neurológicos da Marcha/epidemiologia , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Bloqueadores dos Canais de Potássio/farmacologia , Estudos Prospectivos
16.
Clin Immunol ; 169: 47-57, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27318116

RESUMO

High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8(+)T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1(+)CD8(+)T-cells and of PD-1-expressing CD19(+) B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla Recidivante-Remitente/terapia , Linfócitos T/imunologia , Timo/imunologia , Adulto , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Progressão da Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Avaliação de Resultados em Cuidados de Saúde , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos , Transdução de Sinais/imunologia , Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fatores de Tempo , Transplante Autólogo , Adulto Jovem
17.
Epilepsy Behav ; 54: 95-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26687293

RESUMO

INTRODUCTION: Patients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy- and hard-to-control epilepsies. METHODS: Essentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory - novelty seeking domain. Then, patients were categorized according to seizure control as having easy- and hard-to-control JME. RESULTS: Patients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking - subfactor impulsiveness (p=0.002). SIGNIFICANCE: Our study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos da Memória/diagnóstico , Epilepsia Mioclônica Juvenil/diagnóstico , Fenótipo , Adulto , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Feminino , Seguimentos , Humanos , Comportamento Impulsivo , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Epilepsia Mioclônica Juvenil/epidemiologia , Epilepsia Mioclônica Juvenil/psicologia , Testes Neuropsicológicos , Inventário de Personalidade , Adulto Jovem
18.
Indian J Med Res ; 144(5): 657-660, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28361817

RESUMO

Epilepsy is a highly prevalent chronic neurologic disorder and leads to social, behavioural, health and economic consequences. 'Treatment gap' varies from 10 per cent in developed countries to 75 per cent in low-income countries. Stigma and discrimination related to epilepsy are prevalent worldwide. Electroencephalography (EEG) is considered the most important tool for evaluating the patient with epilepsy. Video-EEG monitoring is an important tool for confirming the seizure type and estimating the epileptogenic zone in the brain. Neuroimaging evaluation is important to determine the aetiology of the epilepsies. Genetic testing has increased the probability of identifying the causes of some types of epilepsies. Epilepsy can be treated in an affordable way with low-cost medications. Refractory epilepsies occur in approximately one-third of recently diagnosed patients with epilepsy. For this group of patients, there are options of surgical treatment, diets and neurostimulation to improve seizure control and quality of life. In poorly organized societies, there is a lack of prioritization of epilepsy in national health policies, limited resources for trained personnel and a shortage of basic antiepileptic medications. There is evidence of improvement in the understanding of epilepsy and a clear progress in the management of epileptic seizures in recent times.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Convulsões/fisiopatologia , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/genética , Humanos , Convulsões/diagnóstico , Convulsões/tratamento farmacológico
19.
Clin Neuropsychol ; 29(6): 836-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26513484

RESUMO

OBJECTIVE: To investigate the reliability and validity of a Brazilian-Portuguese adaptation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). METHOD: A Brazilian sample of 58 multiple sclerosis (MS) patients and 58 healthy controls (HC) were administered the Brazilian-Portuguese BICAMS test battery, comprising the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test Second Edition (CVLT2), and the Brief Visuospatial Memory Test Revised (BVMTR). Mean differences between groups on BICAMS tests were assessed using analysis of covariance (ANCOVA), controlling for age, gender, education, anxiety, and depression. Test-retest data were obtained from 49 of the MS patients, two weeks after the initial assessment. RESULTS: The MS patient group scored significantly lower on all BICAMS tests (CVLT2 F1,110 = 28.99, p < .001; BVMTR F1,110 = 7.77, p < .01; SDMT F1,110 = 21.09, p < .001). Mixed-factor ANCOVAs tested differences in learning curves across trials for CVLT2 and BVMTR. HCs had significantly steeper learning curves on both CVLT2 (F1,111 = 10.82, p < .01) and BVMTR (F1,110 = 7.816, p < .01). These findings support diagnostic validity of the Brazilian-Portuguese adaptation. Test-retest reliability was satisfactory for SDMT, CVLT2, and BVMTR (.86, .84, and .77, respectively). CONCLUSION: The results suggest that this Brazilian version of the BICAMS will be a valid and reliable measure once complete normative data become available.


Assuntos
Transtornos Cognitivos/diagnóstico , Esclerose Múltipla/psicologia , Testes Neuropsicológicos/normas , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
20.
Epilepsy Behav ; 45: 44-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25819744

RESUMO

OBJECTIVE: The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. METHOD: The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5±8.95years old), 20 patients with temporal lobe epilepsy (TLE) (37.7±13.25years old), and 26 healthy controls (31.86±11.25years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. RESULTS: Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p<0.001 and JME vs controls: 28.60 vs 14.12, p<0.001), attentional (JME vs TLE: 21.55 vs 13.45, p<0.001 and JME vs controls: 21.55 vs 14.88, p<0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p<0.001 and JME vs controls: 28.05 vs 16.15, p<0.001). CONCLUSION: Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity.


Assuntos
Epilepsia do Lobo Temporal/psicologia , Comportamento Impulsivo/fisiologia , Epilepsia Mioclônica Juvenil/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
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