(+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy.

Genetic diversity of two Brazilian populations of the Pampas deer (Ozotoceros bezoarticus, Linnaeus 1758)

The Pampas deer (Ozotoceros bezoarticus) is one of the most endangered Neotropical cervid with populations that have been drastically reduced to small and isolated ones, mainly because of its habitat destruction. Random amplified polymorphic DNA (RAPD) markers were used to analyze population divergence and genetic variation within and between two populations corresponding to distinct subspecies. The RAPD markers displayed substantial genetic variation with all animals possessing unique RAPD phenotypes over 105 polymorphic bands produced by 15 primers. An analysis of molecular variance (AMOVA) and a neighbor-joining cluster analysis were performed to assess levels of differentiation between populations. No differentiation was recorded and about 96.0 percent (P < 0.00001) of the total variance was attributable to variation within populations. This result is quite distinct from data obtained by the analysis of the mtDNA control region, and is discussed on the basis of genetic differences between the different markers and the male-biased dispersal patterns generally observed in the mammal species. The data presented herein are potentially useful for future taxonomic and genetic studies in this species, for the monitoring of the genetic variation observed within these populations, and for the development of management guidelines for its conservation.

O Veado-campeiro (Ozotoceros bezoarticus) é uma das espécies de cervídeos neotropical mais ameaçadas devido à destruição de seu hábitat e conseqüente redução e isolamento de suas populações. Marcadores do tipo RAPD (Random amplified polymorphic DNA) foram utilizados na análise da divergência populacional e estimativa da variação genética dentro e entre duas populações correspondentes a diferentes subespécies. Os marcadores RAPD mostraram uma variação genética substancial, sendo que as 105 bandas polimórficas obtidas pelo uso de 15 primers produziram fenótipos únicos para todos os indivíduos analisados. Para avaliar o nível de diferenciação entre as populações, foi realizada uma análise da variância molecular (AMOVA) e uma análise de agrupamento utilizando o método de neighbor-joining. Nenhuma diferenciação foi observada, sendo aproximadamente 96,0 por cento da variação encontrada atribuída à variação dentro das populações estudadas. Este resultado difere do obtido através da análise da região controle do mtDNA, e é discutido levando-se em consideração as diferenças genéticas entre os diferentes marcadores utilizados e o padrão de dispersão geralmente observado nas espécies de mamíferos (realizada principalmente pelos machos). Os dados aqui apresentados poderão ser úteis para futuros estudos taxonômicos e genéticos desta espécie, para o monitoramento da variação genética observada em suas populações e para o desenvolvimento de estratégias de manejo para sua conservação.

Genetic diversity of two Brazilian populations of the Pampas deer (Ozotoceros bezoarticus, Linnaeus 1758).

The Pampas deer (Ozotoceros bezoarticus) is one of the most endangered Neotropical cervid with populations that have been drastically reduced to small and isolated ones, mainly because of its habitat destruction. Random amplified polymorphic DNA (RAPD) markers were used to analyze population divergence and genetic variation within and between two populations corresponding to distinct subspecies. The RAPD markers displayed substantial genetic variation with all animals possessing unique RAPD phenotypes over 105 polymorphic bands produced by 15 primers. An analysis of molecular variance (AMOVA) and a neighbor-joining cluster analysis were performed to assess levels of differentiation between populations. No differentiation was recorded and about 96.0% (P<0.00001) of the total variance was attributable to variation within populations. This result is quite distinct from data obtained by the analysis of the mtDNA control region, and is discussed on the basis of genetic differences between the different markers and the male-biased dispersal patterns generally observed in the mammal species. The data presented herein are potentially useful for future taxonomic and genetic studies in this species, for the monitoring of the genetic variation observed within these populations, and for the development of management guidelines for its conservation.

[The importance of oxygen free radicals in the neonatal period] / Importância dos radicais livres de oxigênio no período neonatal.

OBJECTIVE: Oxygen free radicals are extremely reactive species and they can lead to injury and cell death. The aim of this review is to study the main biochemical aspects of free radical formation and their role as an intermediate mechanism of injury in several neonatal diseases.METHODS: A brief history of oxygen therapy in neonatology and its relationship with complications associated with the production of free radicals. Definition, mechanism of action and antioxidant systems were described. Next, the neonatal factors of increased risk of free radical oxidative injury and the diseases associated with oxygen free radical toxicity were reviewed.RESULTS: Oxygen free radicals are reactive species that although crucial to normal biological processes, can lead to injury and cell death. They are implicated in the pathogenesis of many neonatal diseases such as perinatal asphyxia, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, intracranial hemorrhage, pulmonary hypertension and persistence of ductus arteriosus. Birth is associated with transition to a hyperoxic environment in comparison with uterine environment, which leads to increased generation free radicals. The newborn has undeveloped antioxidant systems and, therefore, may be at increased risk of free radical oxidative injury.CONCLUSIONS: The understanding of neonatal factors involved in the pathogenesis of "oxygen free radical diseases" will lead to the development of new therapies for prevention and treatment of these neonatal diseases.