RESUMO
The 5-HT(2A)-serotonin receptor is a major molecular target for most atypical antipsychotic drugs as well as most hallucinogens, which can exacerbate psychotic symptoms. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT(2A)-serotonin receptor could explain inter-individual variability in atypical antipsychotic and agonist drug response. We examined the in vitro pharmacology of four non-synonymous SNPs, which give rise to T25N, I197V, A447V, and H452Y variant 5-HT(2A)-serotonin receptors. Our data indicate that these non-synonymous SNPs exert statistically significant, although modest, effects on the affinity and functional effects of several currently approved atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone). Also, the 5-HT(2A) receptor SNPs slightly altered the potency and relative efficacy of a small number of selected agonists (2,5-dimethoxy-4-iodoamphetamine, tryptamine, 5-hydroxytryptamine, m-chlorophenylpiperazine, and 5-methoxy-N, N-dimethyltryptamine). In all, our results show that the in vitro pharmacological effects of the SNPs are drug specific.
Assuntos
Antipsicóticos/farmacologia , Polimorfismo de Nucleotídeo Único , Receptor 5-HT2A de Serotonina/genética , Agonistas do Receptor de Serotonina/farmacologia , Ligação Competitiva , Linhagem Celular , Clonagem Molecular , Relação Dose-Resposta a Droga , Humanos , Ligantes , Ensaio Radioligante , Receptor 5-HT2A de Serotonina/biossíntese , Agonistas do Receptor 5-HT2 de Serotonina , TransfecçãoRESUMO
The objective of this study was to investigate the calorie and protein adequacies, to establishoffe operation model and the operational difficulties of the School-Lunch Program in Campinas, Brazil. Six schools randomly selected (1,237 children) were investigated. Calorie and protein consumption were estimated by weighed records. A model food project was developed in order to analyse the city food-service operation. The adequacy values were very low: 48.6 +/- 17.3% for energy and 52.7 +/- 17.2% for protein. The Tukey test indicated that schools did not differ regarding adequacies (alpha = 0.005). The results suggested that the efficiency and/or the impact of Campinas program may be limited by both, lack of resources and several operation failures such as: preparation of large amount of food which is not served to the children; the type of the food served; the ineffective administrative controls; the low supervision frequency, low school garden production and inefficient staff training; as well as the lack of food quality control, evaluations, community participation, nutritional education had integration with health programs.