RESUMO
The anthracycline chemotherapeutic agent doxorubicin is converted by the enzyme carbonyl reductase 1 (CBR1) into its cardiotoxic metabolite doxorubicinol. Cbr1+/- mice have been shown to be protected from doxorubicin-induced cardiotoxicity, and the inhibition of CBR1 activity may be a useful means of ameliorating the side effects of doxorubicin in patients undergoing chemotherapy. Because reduced conversion to doxorubicinol increases circulating levels of the more effective parent drug doxorubicin, it was hypothesized that therapeutic efficacy against tumors might also be enhanced. Cbr1+/- mice were bred to mice transgenic for the polyomavirus middle T antigen (PyVT) to create offspring with palpable mammary tumors. Latency to initial tumor formation was similar in Cbr1+/- and Cbr1+/+ animals. Tumor regression was improved in Cbr1+/- animals, but only in male mice. Western blotting showed a marked sex difference in protein levels, with a much higher expression of Cbr1 in the female kidney and liver. Thus, the combined effects of a naturally low expression and the heterozygous Cbr1 null allele seem to have enhanced tumor regression in Cbr1+/- males. Future efforts to design a clinical CBR1 inhibitor to protect patients from the cardiac side effects of doxorubicin treatment should evaluate the effect of sex on anticancer efficacy.
Assuntos
Oxirredutases do Álcool/genética , Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Oxirredutases do Álcool/metabolismo , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/análogos & derivados , Doxorrubicina/metabolismo , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Neoplasias Mamárias Animais/tratamento farmacológico , Camundongos , Camundongos Mutantes , Camundongos TransgênicosRESUMO
Objetivo: Determinar las creencias relacionadas con la violencia de pareja en los pobladores del Centro Poblado "La Tierra Prometida" (Ica). Materiales y métodos: Se realizó un estudio observacional, descriptivo y transversal en el Centro Poblado "La Tierra Prometida" (Ica), que alberga aproximadamente 1800 familias y 3600 pobladores de 19 a 59 años de edad. La muestra de 361 pobladores se seleccionó mediante muestreo aleatorio multietápico. Resultados: La violencia de pareja fue reportada por 350 (97,0%) entrevistados, en 345 (95,6%) de ellos fue de tipo psicológico y en 271 (75,1%) de tipo físico. Se observó mayor aceptación (de acuerdo o muy de acuerdo) con el enunciado "la mujer no se da cuenta cuando maltrata a su pareja" (75,1%), "el hombre que maltrata a una mujer tiene problemas psicológicos" (73,4%) y "el hombre que se deja maltratar por una mujer tiene problemas psicológicos" (73,2%). La violencia psicológica se asoció con la actividad laboral y el antecedente de violencia infantil (p<0,5); la violencia física se asoció al grado de instrucción (p<0,05). Conclusiones: Las creencias de la población denotan la presencia de patrones culturales que estigmatizan al hombre frente a este problema y que podrían limitar su reconocimiento y denuncia. (AU)
Objective: To determine the beliefs related to intimate partner violence in the settlers of the "Promised Land" Populated Center (Ica). Materials and methods: An observational, descriptive and cross-sectional study was carried out in the "Promised Land" Town, which houses approximately 1,800 families and 3,600 residents aged 19 to 59 years. The sample of 361 inhabitants was selected by multistage random sampling. Results: Partner violence was reported by 350 (97.0%) interviewed persons, it was psychological one in 345 (95.6%) of them and physical type in 271 (75.1%). Greater acceptance was made according to the statement "the woman does not realize when she mistreats her partner" (75.1%), "the man who mistreats a woman has psychological problems" (73, 4%) and "the man who lets himself be mistreated by a woman has psychological problems "(73.2%). Psychological violence was associated with work activity and a history of childhood violence (p <0.5); physical violence was associated with the level of education (p <0.05). Conclusions: The beliefs of the population denote the presence of cultural patterns that are stigmatizing the man and that can be limiting its recognition and denunciation. (AU)