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1.
Br J Neurosurg ; 28(4): 520-2, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24304265

RESUMO

External bleeding from any form of tumour of the central nervous system is unusual. We present a case where this difficult problem was controlled by the use of Gamma Irradiation from a focused delivery system.


Assuntos
Neoplasias Encefálicas/cirurgia , Sistema Nervoso Central/cirurgia , Raios gama , Hemorragias Intracranianas/radioterapia , Idoso , Seguimentos , Humanos , Hemorragias Intracranianas/cirurgia , Masculino , Resultado do Tratamento
2.
Eur J Pharmacol ; 883: 173377, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32687920

RESUMO

Lithium, commonly used to treat bipolar disorder, potentiates the ability of the muscarinic agonist pilocarpine to induce seizures in rodents. As this potentiation by lithium is reversed by the administration of myo-inositol, the potentiation may be mediated by inhibition of inositol monophosphatase (IMPase), a known target of lithium. Recently, we demonstrated that ebselen is a 'lithium mimetic' in regard to behaviours in both mice and man. Ebselen inhibits IMPase in vitro and lowers myo-inositol in vivo in the brains of mice and men, making ebselen the only known inhibitor of IMPase, other than lithium, that penetrates the blood-brain barrier. Our objective was to determine the effects of ebselen on sensitization to pilocarpine-induced seizures and neural activity. We administered ebselen at different doses and time intervals to mice, followed by injection of a sub-seizure dose of pilocarpine. We assessed seizure and neural activity by a subjective seizure rating scale, by monitoring tremors, and by induction of the immediate early gene c-fos. In contrast to lithium, ebselen did not potentiate the ability of pilocarpine to induce seizures. Unexpectedly, ebselen inhibited pilocarpine-induced tremor as well as pilocarpine-induced increases in c-fos mRNA levels. Both lithium and ebselen inhibit a common target, IMPase, but only lithium potentiates pilocarpine-induced seizures, consistent with their polypharmacology at diverse molecular targets. We conclude that ebselen does not potentiate pilocarpine-induced seizures and instead, reduces pilocarpine-mediated neural activation. This lack of potentiation of muscarinic sensitization may be one reason for the lack of side-effects observed with ebselen treatment clinically.


Assuntos
Anticonvulsivantes/farmacologia , Azóis/farmacologia , Encéfalo/efeitos dos fármacos , Cloreto de Lítio/toxicidade , Neurônios/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Pilocarpina , Convulsões/prevenção & controle , Animais , Anticonvulsivantes/toxicidade , Azóis/toxicidade , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Células CHO , Sinalização do Cálcio/efeitos dos fármacos , Cricetulus , Modelos Animais de Doenças , Fosfatos de Inositol/metabolismo , Isoindóis , Masculino , Camundongos , Neurônios/metabolismo , Compostos Organosselênicos/toxicidade , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Convulsões/induzido quimicamente , Convulsões/metabolismo , Convulsões/fisiopatologia
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