Epigenetic Factors in Cancer Risk: Effect of Chemical Carcinogens on Global DNA Methylation Pattern in Human TK6 Cells

In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6) cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2′-deoxycytidine. The effect of exposure on 5-methyl-2′-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

Background: Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. Methodology: The metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Principal Findings: Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. Conclusion: These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction

Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AAs that were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essential AAs were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels. Conclusion: We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate, which together reduce fetal AA demand. © 2013 International Pediatric Research Foundation, Inc

Factores psicosociales asociados a un alto, medio y bajo riesgo de síntomas depresivos en el posparto inmediato Psychosocial factors associated to low, medium and high risk of depressive symptoms in the immediate postpartum period

OBJETIVOS: evaluar factores psicosociales asociados a síntomas depresivos en el posparto inmediato. MÉTODOS: 45 mujeres puérperas de un hospital público de Buenos Aires, Argentina, fueron entrevistadas entre el 1er y el 3er día posparto, de marzo-diciembre 2010. La Escala de Depresión Posnatal de Edimburgo (EPDS) fue administrada para evaluar síntomas depresivos. La entrevista psicológica perinatal (EPP) fue administrada para detectar variables psicosociales. A partir de los resultados obtenidos en la EPDS, se separó la muestra en tres grupos con diferentes grados de riesgo de sintomatología depresiva: "negativas o de bajo riesgo", "positivas de riesgo medio" y "positivas de alto riesgo". Los puntajes de corte utilizados fueron 9 y 19. RESULTADOS: se encontraron diferencias significativas entre los tres grupos con violencia familiar, migración, historia previa de depresión, presencia de síntomas depresivos durante el embarazo y mayor cantidad de estresores. CONCLUSIONES: el establecimiento de los dos puntajes de corte en la EPDS permite una detección temprana de las mujeres que presentan síntomas depresivos. Se sugiere la utilidad del puntaje de corte de 19 para la detección temprana de mujeres con mayor riesgo de desarrollar depresión posparto.<br>OBJECTIVES: evaluate psychosocial factors associated to depressive symptoms during the immediate postpartum period. METHODS: a total of 45 argentine puerperal women hospitalized in a public maternal hospital of Buenos Aires, Argentina, were interviewed on the 1st and 3rd day postpartum from March to December 2010. Aiming to assess the presence of depressive symptoms, the Edinburgh Postnatal Depression Scale (EPDS) was administrated. The Perinatal Psychological Interview was administrated to explore psychosocial variables. Based on the scores obtained in the EPDS, the sample was separated in three different groups with increasing risk of depressive symptomatology: "negative or low risk", "positive medium risk" and "positive high risk". Cut-off scores were 9 and 19 points. RESULTS: out of the total psychosocial variables analyzed, statistically significant differences were found among the three groups regarding family violence, migration, previous history of depression, depressive symptoms during pregnancy and increasing number of life events. CONCLUSIONS: the setting of two cut-off scores in EPDS allows the early detection of women with depressive symptoms. It is suggested the usefulness of cut-off value of 19 for early detection of women at high risk to developing postpartum depression