RESUMO
We report a family with complex febrile seizures (FS). The proband is a 15-year-old boy with seizures that persisted beyond 6 years of age. His father, aunt, and cousin also have the histories of FS until 8, 9, and 8 years old, respectively. A base substitution 5569G-->T of voltage-gated sodium channel alpha-1 subunit gene was found in DNA derived from the affected members of this family.
Assuntos
Epilepsia Generalizada/genética , Saúde da Família , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Convulsões Febris/genética , Canais de Sódio/genética , Análise Mutacional de DNA/métodos , Epilepsia Generalizada/complicações , Humanos , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Proteínas do Tecido Nervoso/sangue , Linhagem , Convulsões Febris/sangue , Convulsões Febris/complicações , Homologia de Sequência , Canais de Sódio/sangueRESUMO
The cytotoxic effects of HMN-176 ((E)-4-[[2-N-[4-methoxybenzenesulfonyl] amino] stilbazole] 1-oxide; a newly synthesized compound, were evaluated and compared with those of the clinically used antitumor agents cis-platinum, adriamycin, etoposide, taxol, and vincristine in 22 human tumor cell lines isolated from various organs. HMN-176 exhibited potent cytotoxicity with IC(50) values in the nM range, and the variance of its cytotoxic efficacy was remarkably small. Drug-resistant cell lines also showed low cross-resistance to HMN-176 corresponding to overall resistance indices of less than 14.3. HMN-214 was synthesized as an oral prodrug because of the poor oral absorption of HMN-176 itself. Pharmacokinetic studies showed that HMN-214 was an acceptable oral prodrug of HMN-176. In the in vivo analysis of the schedule-dependency of HMN-214, the repeated administration for over 5 days elicited potent antitumor activity, as expected from the exposure-dependency of the cytotoxicity of HMN-176 and from the cytometric studies. The antitumor activity of HMN-214 against human tumor xenografts was equal or superior to that of clinically available agents, including cis-platinum, adriamycin, vincristine, and UFT without severe toxicity such as neurotoxicity. Because of its good activity in preclinical trials, HMN-214 has entered Phase I clinical trials in the USA.