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1.
Pediatr Neurol ; 147: 1-8, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499552

RESUMO

BACKGROUND: The purpose of this study was to determine the efficacy of lacosamide (LCM) on interictal epileptiform discharges (IEDs) and evaluate the relationships between IEDs and seizure outcome in pediatric patients with focal epilepsy. METHODS: Patient inclusion criteria included (1) newly diagnosed focal epilepsy with unknown etiology; and (2) electroencephalogram recorded twice (before and after starting LCM) under the same conditions. The difference between the highest number of IEDs over five successive minutes (IEDs/5 min) and the location of IEDs was determined. Seizure outcome was evaluated one year after achieving the maintenance dose of LCM. Responders were identified as showing a ≥50% reduction in the pre-LCM seizure frequency. RESULTS: Of 22 patients, 10 showed an increase in IEDs/5 min after starting LCM. The median IEDs/5 min before and after starting LCM was not significantly different, at 1.5 (interquartile range: 0, 31.75) and 10.5 (0, 80.5), respectively. No relationship was identified between the difference in IEDs/5 min and seizure outcome. Patients with multiple regional or diffuse IEDs had significantly poorer seizure outcome compared with patients without those IEDs (P = 0.036 and P = 0.039, respectively). Of 10 patients with single regional IEDs, a tendency of IEDs to disappear was observed between patients with frontal and non-frontal IEDs. CONCLUSION: The effects of LCM on the number of IEDs may be unrelated to seizure outcome. LCM may be ineffective at improving seizure outcomes in patients with multiple regional or diffuse IEDs.


Assuntos
Epilepsias Parciais , Humanos , Criança , Lacosamida , Epilepsias Parciais/tratamento farmacológico , Convulsões , Eletroencefalografia
2.
Nanotechnology ; 28(13): 135101, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28240988

RESUMO

Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines.


Assuntos
Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Administração Intravenosa , Animais , Plaquetas/metabolismo , Feminino , Hipotermia Induzida , Células de Kupffer/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Nanopartículas/toxicidade , Fator de Ativação de Plaquetas/metabolismo , Dióxido de Silício/toxicidade , Testes de Toxicidade Aguda
3.
Nat Nanotechnol ; 11(9): 808-16, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27240418

RESUMO

Many people suffer from metal allergy, and the recently demonstrated presence of naturally occurring metal nanoparticles in our environment could present a new candidate for inducing metal allergy. Here, we show that mice pretreated with silver nanoparticles (nAg) and lipopolysaccharides, but not with the silver ions that are thought to cause allergies, developed allergic inflammation in response to the silver. nAg-induced acquired immune responses depended on CD4(+) T cells and elicited IL-17A-mediated inflammation, similar to that observed in human metal allergy. Nickel nanoparticles also caused sensitization in the mice, whereas gold and silica nanoparticles, which are minimally ionizable, did not. Quantitative analysis of the silver distribution suggested that small nAg (≤10 nm) transferred to the draining lymph node and released ions more readily than large nAg (>10 nm). These results suggest that metal nanoparticles served as ion carriers to enable metal sensitization. Our data demonstrate a potentially new trigger for metal allergy.


Assuntos
Hipersensibilidade a Drogas , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Células Cultivadas , Orelha/diagnóstico por imagem , Orelha/patologia , Feminino , Linfonodos/citologia , Linfonodos/diagnóstico por imagem , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Tamanho da Partícula , Prata/química , Linfócitos T
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