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The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.
Assuntos
Epilepsia do Lobo Temporal , MicroRNAs , Canal de Sódio Disparado por Voltagem NAV1.1 , Polimorfismo de Nucleotídeo Único , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , MicroRNAs/genética , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Masculino , Brasil , Adulto , Predisposição Genética para Doença , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Genótipo , Estudos de Coortes , Alelos , Frequência do Gene , Adolescente , Estudos de Casos e ControlesRESUMO
Introduction: Epilepsy affects about 50 million people worldwide, 80% of whom live in low- and middle-income countries. In Brazil, epidemiological studies are outdated and restricted to specific regions, mostly due to the continental size of country. Objective: We aimed to present the first evidence-based study on the epidemiological aspects of individuals with epilepsy, mapping the characteristics of this disease in a referral center in a region of Southeast Brazil. Methods: A retrospective study was carried out from January 2010 to March 2021. Patients were selected according to the International League Against Epilepsy Criteria. Results: From a total of 618 selected patients, 317 (51.3%) were men and 301 (48.7%) were women with an average age of 34.03 ± 20.66 years. The average age at the first seizure was 15.16 ± 17.61 years. The prevalence ratio was 1.30 cases/1,000 habitants. Childhood febrile seizure was present in 44 patients (7.9%) and family history of epilepsy in 231 (37.4%) patients. The predominant type of seizure was focal in 401 (64.9%) patients. The most frequent etiologies were structural in 254 (41.1%) patients and unknown in 238 (38.5%) patients. Most of the patients' treatments were based on anti-seizure drugs in monotherapy [389 (62.9%)] with 398 (64.4%) drug-responsive patients. Conclusions: Our epilepsy prevalence rate was lower than other studies in the Southeast Region of Brazil. In addition, the structural epilepsy type was predominant in our study compared with unknown causes, which is more frequent in other Brazilian regions and worldwide studies. The differences may be attributed to our region, which presents a high prevalence of neuroinfection, specially neurocysticercosis, and a referral center for traumatic brain injury. Moreover, the contrasting results reinforce the need for an adequate epidemiological assessment of epilepsy incidence in a region of Southeast Brazil.
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BACKGROUND: Gliomas are aggressive and resilient tumors. Progression to advanced stages of malignancy, characterized by cell anaplasia, necrosis, and reduced response to conventional surgery or therapeutic adjuvant, are critical challenges in glioma therapy. Relapse of the disease poses a considerable challenge for management. Hence, new compounds are required to improve therapeutic response. As hydrolyzed rutin (HR), a compound modified via rutin deglycosylation, as well as some flavonoids demonstrated antiproliferative effect for glioblastoma, these are considered potential epigenetic drugs. OBJECTIVE: The purpose of this study was to determine the antitumor activity and evaluate the potential for modifying tumor aggressivity of rutin hydrolysates for treating both primary and relapsed glioblastoma. METHODS: The glioblastoma cell line, U251, was used for analyzing cell cycle inhibition and apoptosis and for establishing the GBM mouse model. Mice with GBM were treated with HR to verify antitumor activity. Histological analysis was used to evaluate HR interference in aggressive behavior and glioma grade. Immunohistochemistry, comet assay, and thiobarbituric acid reactive substance (TBARS) values were used to evaluate the mechanism of HR action. RESULTS: HR is an antiproliferative and antitumoral compound that inhibits the cell cycle via a p53- independent pathway. HR reduces tumor growth and aggression, mainly by decreasing mitosis and necrosis rates without genotoxicity, which is suggestive of epigenetic modulation. CONCLUSION: HR possesses antitumor activity and decreases anaplasia in glioblastoma, inhibiting progression to malignant stages of the disease. HR can improve the effectiveness of response to conventional therapy, which has a crucial role in recurrent glioma.
Assuntos
Anaplasia/complicações , Anaplasia/prevenção & controle , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/complicações , Glioblastoma/tratamento farmacológico , Rutina/farmacologia , Rutina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Hidrólise , Camundongos , Recidiva , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The optogenetic tools have been described as valuable techniques to study neural activity through light stimulation, as well as potential neuromodulator approaches in the management of several central nervous system (CNS) diseases. Since the first bacteriorhodopsin protein described as a single-component light-activated regulator of transmembrane ion flow description, in 1980's, the focus has been on channel proteins for neurobiology; however, the advances in engineering techniques showed involvement changes in cellular biological behavior in several types of proteins involved in cell cytoskeleton regulation, motility and gene expression. Although the use of this technology has been published in many papers, a question still remains regarding real results and potential clinical applicability in CNS diseases, as well as the publications scarcity that systematically analyses the published results. Lastly, the aim of this review is to discuss the experimental results, molecular mechanisms and potential clinical applications of optogenetic tools in epilepsy and depression treatment, as well as its applicability in the treatment of CNS tumors.
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BACKGROUND AND OBJECTIVE: This paper was based on a literature search of PubMed and Scielo databases using the keywords "Flavonoids, Neuroprotection, Quercetin, Rutin, Isoquercitrin, Alzheimer, Parkinson, Huntington" and combinations of all the words. METHOD: We collected relevant publications, during the period of 2000 to 2016, emphasizing in vivo and in vitro studies with neurological assessment of flavonol's potentials, as well as classifying studies according to evidence levels, in order to elucidate evidence-based literature and its application on clinical research. In addition, we highlight the importance of flavonols in modern research fields, indicating their neuroprotective potential and use thereof as preventive and therapeutic treatment of numerous neurodegenerative disease. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, represent worldwide a major health problem with great financial impact. They are multifactorial diseases, hallmarked by similar pathogenesis that covers conditions such as oxidative stress, formation of free radicals, abnormal protein dynamics (degradation and aggregation), mitochondrial dysfunction, lipid peroxidation and cellular death or senescence. Flavonols are polyphenolic compounds, widely distributed in the plant kingdom and found in high concentrations in vegetables, fruits and teas. Their neuroprotective effects are mainly related to their antioxidant, anti-proliferative and anti-inflammatory properties. CONCLUSION: It was this paper's intention to contribute with an evidence analysis of recent studies approaching neuroprotective effects of flavonols and the potential to conduct human clinical studies.
Assuntos
Modelos Animais de Doenças , Flavonóis/farmacologia , Flavonóis/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Animais , HumanosRESUMO
Os autores apresentam a experiência adquirida com parte dos pacientes submetidos às derivaçoes ventricular, peritoneal e atrial, desde o início do Serviço de Neurocirurgia, em 1983. A técnica operatória, apesar de simples, tem ainda muitas controvérsias, em virtude do número elevado de revisoes que os sistemas de inúmeras procedências necessitam, levando ao aparecimento de complicaçoes, algumas vezes graves. Com estas ressalvas, a mortalidade foi de 14,28 por cento, comparável a outras séries. O primeiro shunt peritoneal é creditado a Ferguson, em 1898. Foi feito com agulha de prata, comunicando o espaço subaracnóide com o peritônio, através do corpo vertebral de L5. Este e outros métodos utilizados em tempos mais remotos falharam e novas tentativas somente foram feitas e publicadas 25 anos após. Quando a válvula Spitz Holter e os cateteres flexíveis começaram a ser usados, a cirurgia do shunting começou a ficar mais popular. Desde entao vem-se notando que as complicaçoes com a DVA usada na época nao eram tao infreqüentes. A partir de 1967, Ames & Murgathi chamaram a atençao para a possibilidade de utilizar a cavidade peritoneal para o desvio ventricular. Trabalhos mais recentes têm mostrado que tanto a DVA quanto a DVP sao eficientes para o tratamento dos hidrocéfalos, existindo significantes vantagens para o sistema peritoneal quando se leva em conta a gravidade das complicaçoes com a DVA.
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Lesões Encefálicas/cirurgia , Aqueduto do Mesencéfalo/cirurgia , Fossa Craniana Posterior/cirurgia , Cisticercose/cirurgia , Doenças do Sistema Nervoso/cirurgia , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Meningite/cirurgia , Meningomielocele/cirurgia , Derivação Ventriculoperitoneal , Derivação Ventriculoperitoneal/efeitos adversos , Derivações do Líquido CefalorraquidianoRESUMO
The authors studied the angiographic aspects in nine cases of central nervous system blastomicosis, concluding that the images suggests "A vascular Lesions" with small shift of the cerebral blood vessels. They found only one case with slight opacification
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Angiografia , Sistema Nervoso Central , ParacoccidioidomicoseRESUMO
Os meningeomas constituem frequente causa de compressöes medulares. Estes tumores, quando localizados no interior do canal vertebral, podem causar síndrome de compressäo medular e ou radicular. Constituem patologia benigna e quando precocemente diagnosticados e operados, permitem aos pacientes, na maioria das vezes, um bom prognóstico. No entanto, quando o diagnóstico e a cirurgia säo retardados, a pressäo exercida pelo tumor pode interferir na circulaçäo e nutriçäo da medula, causando dano irreparavel em funçäo do processo isquemico decorrente. É fundamental, portanto, que além dos neurologistas e neurocirurgiöes, os demais médicos estejam familiarizados com os aspectos que dizem respeito aos meningeomas intra-raquianos. Este trabalho tem por finalidade, a análise que observamos em 35 casos de meningeomas intra-raquianos, catalogados entre os casos de meningeomas diagnosticados e operados ao longo de vários anos na Disciplina de Neurocirurgia da Escola Paulista de Medicina
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MeningiomaRESUMO
Os tumores intracranianos representam uma das neoplasias mais freqüentes que ocorrem na infância e adolescência, superados somente pela leucemia. Na infância, os tumores intracranianos säo também um problema diagnóstico, porque a maior parte deles produz poucos sintomas, muitas vezes atípicos e facilmente confundíveis com patologias próprias da criança. Para sua detecçäo, é de decisiva importância que o médico que examina a criança tenha isto em mente e que considere tumor intracraniano como diagnóstico diferencial toda vez que exista um desvio, mesmo discreto, do padräo intelectual ou do comportamento da criança, havendo ou näo alteraçäo funcional de natureza somática ou neurológica presentes, visto que o diagnóstico precoce pode levar a menores riscos operatórios, menor morbilidade e, muitas vezes, à recuperaçäo completa da criança. A bibliografia a esse respeito, em nosso meio, é escassa, sendo, em sua maior parte, relato de casos isolados ou determinados subgrupos histológicos ou topográficos, contando-se somente poucos trabalhos de análise geral do problema. O propósito deste estudo é analisar os tumores intracranianos em crianças do nosso meio, quanto aos aspectos de idade, sexo, localizaçäo e natureza, com o que esperamos poder contribuir para um melhor conhecimento deste grave problema
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Lactente , Pré-Escolar , Criança , Adolescente , Humanos , Masculino , Feminino , Neoplasias EncefálicasRESUMO
Os tumores intracranianos representam uma das neoplasias mais frequentes que ocorrem na infancia e adolescencia, superado somente pela leucemia. Na infancia, os tumores intracranianos sao tambem um problema diagnostico, porque a maior partes deles produz poucos sintomas, muitas vezes atipicos e facilmente confundiveis com patologia proprias das criancas. Para sua deteccao, e de decisiva importancia que o medico que examina a crianca tenha isto em mente e que considere tumor intracraniano como diagnostico diferencial toda vez que exista um desvio, mesmo discreto, do padrao intelectual ou do comportamento da crianca, havendo ou nao alteracao funcional de natureza somatica o diagnostico precoce pode levar a menores riscos operatorios, menor mortabilidade e, muitas vezes, a recuperacao completa da crianca. A bibliografia a esse respeito, em nosso meio, e escassa, sendo, em sua maior parte, relato de casos isolados ou determinados subgrupos histologicos ou topograficos, contando-se somente poucos trabalhos de analise feral do problema. O proposito deste estudo e analisar os tumores intracranianos em criancas do nosso meio, quanto aos aspectos de idade, sexo, localizacao e natureza, com o que esperamos poder contribuir para um melhor conhecimento deste grave problema.