Prenatal malnutrition is responsible for the onset of alterations in renal Na(+) transport in the adult offspring. Here we investigated the molecular mechanisms by which increased formation of reactive oxygen species during prenatal malnutrition affects the pathways that couple angiotensin II (Ang II) receptors (AT(1)R and AT(2)R) to kidney Na(+)-ATPase in adulthood, and how maternal treatment with α-tocopherol can prevent alterations in the main regulatory cascade of the pump. The experiments were carried out on the adult progeny of control and malnourished dams during pregnancy that did or did not receive α-tocopherol during lactation. Malnutrition during pregnancy increased maternal hepatic and adult offspring renal malondialdehyde levels, which returned to control after supplementation with α-tocopherol. In the adult offspring, placental malnutrition programmed: decrease in Na(+)-ATPase activity, loss of the physiological stimulation of this pump by Ang II, up-regulation of AT(1)R and AT(2)R, decrease in membrane PKC activity, selective decrease of the PKCε isoform expression, and increase in PKA activity with no change in PKA α-catalytic subunit expression. These alterations were reprogrammed to normal levels by α-tocopherol during lactation. The influence of α-tocopherol on the signaling machinery in adult offspring indicates selective non-antioxidant effects at the gene transcription and protein synthesis levels.

Vaccination coverage is decreasing worldwide, favoring the potential reemergence of vaccinepreventable diseases. In this study, we performed a longitudinal characterization of vaccination coverage in Brazil and compared the profiles between the distinct regions in the country to test whether there has been a substantial change over the last 5 years. Methods: De-identified publicly available data were retrieved from the repository of the Brazilian Ministry of Health, comprising detailed information on vaccination coverage in all age groups between 1994 and 2019. The vaccination coverage for the whole country and for each Brazilian region, by year, was examined, and a time-series pattern analysis was performed. Results: A significant decrease in overall vaccination coverage across the country regions was observed between 2017 and 2019, especially in childhood immunization. A reduction in BCG, hepatitis B, influenza, and rotavirus vaccine coverage was observed. Conversely, vaccines against measles, mumps, rubella, varicella, and meningococcus showed an increase in coverage. Region-specific changes in vaccination patterns within the study period were observed. Conclusions: A substantial reduction in vaccination coverage was detected in Brazil, a country already highly susceptible to the emergence of epidemic infectious diseases. Continuing evaluation of the immunization program actions may help to improve vaccination coverage and prevent new epidemics.

BackgroundSeveral studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na+-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated.Methodology/Principal FindingsFemale rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na++K+)ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K+. Programming doubled the ouabain-insensitive Na+-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT1 and decreased the expression of AT2 receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT2 receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na+ excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days.Conclusions/SignificanceMaternal protein restriction during lactation results in alterations in GFR, renal Na+ handling and in components of the Ang II-linked regulatory pathway of renal Na+ reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood.