RESUMO
Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped versions of 4 such as the succinyl derivative 5 can be administered by the iv route at more than 10 times the LD(50) of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.
Assuntos
Antineoplásicos/síntese química , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/síntese química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Pró-Fármacos/síntese química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Cromatografia Líquida de Alta Pressão , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/toxicidade , Estabilidade de Medicamentos , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Oligopeptídeos/toxicidade , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/toxicidade , Soluções , Testes de Toxicidade Aguda , Células Tumorais Cultivadas , Ultrafiltração , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A total of 436 milk samples from non-infected and 80 from infected quarters were investigated: 24.5% of the samples collected from non-infected and 55% of those collected from infected quarters were positive. Normal milk yielded not less than 16 different species and among them many potentially pathogenic yeast species such as C. parapsilosis, C. guilliermondii, C. tropicalis, C. glabrata and T. asahii, all five able to grow at 40 degrees C. In contrast, the yeasts isolated from infected quarters were from 3 species: C. kefyr, C. catenulata and C. lambica, which were also among the yeasts species recovered from normal milk. Among the three species, only one i.e. Candida kefyr is able to grow above 40 degrees C and from there can be considered as potentially pathogenic, even if bacterial association is necessary to cause mastitis.
