Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells

Metformin (dimethyl-biguanide) is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays) and in mice (micronucleus assays). Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

Profile of micronucleus frequencies and DNA damage in different species of fish in a eutrophic tropical lake

Lake Paranoá is a tropical reservoir for the City of Brasilia, which became eutrophic due to inadequate sewage treatment associated with intensive population growth. At present, two wastewater treatment plants are capable of processing up to 95% of the domestic sewage, thereby successfully reducing eutrophization. We evaluated both genotoxic and cytotoxic parameters in several fish species (Geophagus brasiliensis, Cichla temensis, Hoplias malabaricus, Astyanax bimaculatus lacustres, Oreochromis niloticus, Cyprinus carpio and Steindachnerina insculpita) by using the micronucleus (MN) test, the comet assay and nuclear abnormality assessment in peripheral erythrocytes. The highest frequencies of MN were found in Cichla temensis and Hoplias malabaricus, which were statistically significant when compared to the other species. However, Steindachnerina insculpita (a detritivorous and lake-floor feeder species) showed the highest index of DNA damage in the comet assay, followed by C. temensis (piscivorous). Nuclear abnormalities, such as binucleated, blebbed, lobed and notched cells, were used as evidence of cytotoxicity. Oreochromis niloticus followed by Hoplias malaricus, ominivorous/detritivotous and piscivorous species, respectively, presented the highest frequency of nuclear abnormalities, especially notched cells, while the herbivorous Astyanax bimaculatus lacustres showed the lowest frequency compared to the other species studied. Thus, for biomonitoring aquatic genotoxins under field conditions, the food web should also be considered.

Pós-graduaçäo na área médica no Brasil: necessidades e alternativas estruturais / Pos-graduation in Brazilian medicine: necessity and alternatives

A relaçäo linear entre desenvolvimento científico e atividade de pós-graduaçäo quando confrontado com o estruturalismo das carreiras ligadas à saúde, especificamente na área médica, trouxe no Brasil desafios institucionais para conciliar os objetivos de carreira científica e acadêmica com as carreiras profissionais na área da saúde. Modelos acadêmicos com características curriculares diversas geraram diferentes programaçöes acadêmicas cujos resultados, hoje passíveis de avaliaçäo, denunciam uma necessidade urgente de alternativas que ofereçam maiores oportunidades aos profissionais brasileiros na área de saúde. Uma sinopse da evoluçäo histórica da pós-graduaçäo na área médica em comparaçäo com as ciências da saúde é discutida e apresentado uma proposta acadêmica valorizando a exigente formaçäo profissional (principalmente médica) dentro de um controle de qualidade cintífica de aceitaçäo universal. Portanto, seguindo as tendências atuais da pós-graduaçäo em reduzir o tempo de formaçäo do mestre e doutor.

Making sense of the hair zinc literature: where do we go from here?

Los autores hacen una revisión crítica de la literatura sobre los estudios del zinc encontrado en el cabello, anotando las principales contribuciones al respecto. Sugieren ciertas explicaciones, así como algunas soluciones con miras a terminar con la confusión existente a este particular. Se recomienda que el primer paso es medir con confiabilidad solamente el zinc de origen endógeno. Por consiguiente, el estado metabólico del zinc debe ser operacionalmente definido en función del zinc detectado en el cabello. De esta forma, cada una de las variables tendría que ser identificada, cuantificada y controlada. esas variables, cabe agregar, deberían incluir las diferencias en el metabolismo del zinc. Solamente así podrá obtenerse el valor referencial básico del zinc encontrado en el cabello. En la actualidad, los investigadores deberían buscar la relación funcional y no solamente el significado estadístico entre la concentración del zinc en el cabello y el estado metabólico del mismo. A la vez, habría que ratificar y comprobar los hallazgos del gran número de estudios de que se da cuenta en este trabajo, mediante la repetición de estudios de experimentación en animales