RESUMO
OBJECTIVE: Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 to 5 years. Neuronal cell death offers a potential target for therapeutic intervention. Ursodeoxycholic acid is a cytoprotective, endogenous bile acid that has been shown to be neuroprotective in experimental Huntington and Alzheimer diseases, retinal degeneration, and ischemic and hemorrhagic stroke. The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration. METHODS: Eighteen patients were randomly assigned to receive ursodeoxycholic acid at doses of 15, 30, and 50 mg/kg of body weight per day. Serum and cerebrospinal fluid were obtained for analysis after 4 weeks of treatment. Treatment-emergent clinical and laboratory events were monitored weekly. RESULTS: Our data indicated that ursodeoxycholic acid is well tolerated by all subjects at all doses. We also showed that ursodeoxycholic acid is well absorbed after oral administration and crosses the blood-brain barrier in a dose-dependent manner. CONCLUSIONS: These results show excellent safety and tolerability of ursodeoxycholic acid. The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis.
Assuntos
Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Esclerose Lateral Amiotrófica/tratamento farmacológico , Colagogos e Coleréticos/líquido cefalorraquidiano , Colagogos e Coleréticos/uso terapêutico , Ácido Ursodesoxicólico/líquido cefalorraquidiano , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Idoso , Esclerose Lateral Amiotrófica/sangue , Análise de Variância , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/líquido cefalorraquidiano , Barreira Hematoencefálica/efeitos dos fármacos , Colagogos e Coleréticos/efeitos adversos , Colagogos e Coleréticos/sangue , Colagogos e Coleréticos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Ácido Ursodesoxicólico/efeitos adversos , Ácido Ursodesoxicólico/sangue , Ácido Ursodesoxicólico/farmacologiaRESUMO
This research examined whether mothers' expectations about their children's drinking behavior influenced their children's future alcohol use through self-fulfilling prophecies. It also investigated whether children's self-esteem, family social class, or the valence of mother expectations moderated this process. Analyses of longitudinal data from 505 mother-child dyads yielded results consistent with a self-fulfilling prophecy. The inaccurate portion of mother expectations predicted children's future alcohol use after accounting for relevant control variables. Moderation analyses indicated that this effect was stronger among higher self-esteem children and when mother expectations were positively valenced (i.e., when mothers underestimated their children's future alcohol use). The findings are discussed in terms of parent-child relationship quality, peer influences, self theories, and out-group stereotypes.