RESUMO
BACKGROUND AND AIMS: Tuberculosis (TB) is a major worldwide health problem in part due to the lack of new drugs and the emergence of multidrug-resistant strains (MDR). The aim of this study was to select anti-tuberculosis drug candidates from a collection of 69 synthetic sphingosine-ethambutol analogues through in vitro and in vivo evaluations. METHODS: The 69 compounds were evaluated in vitro against two Mycobacterium tuberculosis strains, a drug susceptible (H37Rv) and a MDR clinical isolate (CIBIN-99). Four selected compounds, those that exhibited the highest potency in vitro, were tested in vivo using a model of progressive TB in BALB/c mice infected with the drug susceptible strain, either alone or combined with conventional chemotherapy, as well as in mice infected with the MDR strain. The acute toxicity was evaluated on male and female adult BALB/c mice. RESULTS: Ten of the evaluated compounds resulted more potent in vitro than ethambutol. The experimental compound 2b (2-aminopalmitol benzyl ether) was the most efficacious and also showed additive effects in combination with conventional chemotherapy. It did not exhibit toxicity (LD50 >2000 mg/kg). CONCLUSIONS: Compound 2b can be considered as a new drug candidate to continue its development against M. tuberculosis MDR strains.
Assuntos
Antituberculosos/farmacologia , Etambutol/análogos & derivados , Etambutol/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Esfingosina/análogos & derivados , Animais , Farmacorresistência Bacteriana Múltipla , Etambutol/química , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Esfingosina/química , Esfingosina/farmacologia , Relação Estrutura-Atividade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
Fundamento: el objetivo principal de este estudio fue investigar la fuerza de asociación entre la práctica de la lactancia materna exclusiva y un grupo de factores relacionados con la lactancia materna en una población cerrada atendida en un hospital privado administrado por una empresa cervecera mexicana para atender a sus trabajadores. Material y métodos: se realizó un estudio hospitalario retrospectivo de casos y controles no pareados. De enero de 2001 a enero de 2002, se estudió una muestra de 124 parejas madre hijo en una unidad médica privada en Monterrey, México. Se determinó la asociación entre lactancia materna exclusiva y 11 factores relacionados por análisis bivariado para calcular razones de momios. Resultados: la consejería en lactancia y el contacto temprano entre las parejas madre hijo se encontraron asociadas positivamente a la lactancia materna exclusiva. Conclusión: la consejería en lactancia y el contacto temprano favorecen la lactancia materna exclusiva y se propone promoverlos en otras poblaciones.
Background: The aim of this study was to assess the association between exclusive breastfeeding (EBF) and some factors that may influence breastfeeding in a closely related population attending a private hospital sponsored by a major Mexican brewing company. Materials and methods: We carried out a retrospective hospital based unmatched case control study. A sample of 124 mother-newborn couples was interviewed in a private medical unit in Monterrey, Mexico, from January 2001 to January 2002. The association between EBF and 11 explanatory factors was analyzed by logistic regression analysis. Results: Counseling and early contact between mother-newborn couples were positively associated with EBF. Conclusion: Counseling and early contact improve EBF practice. We believe these two practices would favor better adherence to EBF in other populations.
