Language Impairment in Children of Mothers with Gestational Diabetes, Preeclampsia, and Preterm Delivery: Current Hypothesis and Potential Underlying Mechanisms : Language Impartment and Pregnancy Complications.

Many conditions may impair or delay language development, including socioeconomic status, parent's education, or intrauterine environment. Accordingly, increasing evidence has described that pregnancy complications, including gestational diabetes mellitus (GDM), preeclampsia, and preterm delivery, are associated with the offspring's impaired neurodevelopment. Since language is one of the high brain functions, alterations in this function are another sign of neurodevelopment impairment. How these maternal conditions may generate language impairment has yet to be entirely understood. However, since language development requires adequate structural formation and function/connectivity of the brain, these processes must be affected by alterations in maternal conditions. However, the underlying mechanisms of these structural alterations are largely unknown. This manuscript critically analyzes the literature focused on the risk of developing language impairment in children of mothers with GDM, preeclampsia, and preterm delivery. Furthermore, we highlight potential underlying molecular mechanisms associated with these alterations, such as neuroinflammatory and metabolic and cerebrovascular alterations.

Acoustic parameters and salivary IL-6 levels in overweight and obese teachers.

OBJECTIVE: Either obesity or vocal loading task leads to elevation of proinflammatory cytokines such as interleukin 6 (IL-6). However, it is unknown whether vocal parameters after vocal loading are correlated with body mass index (BMI) or IL-6. We hypothesize that vocal loading induces an elevation of acoustic parameters of voice and salivary IL-6 in overweight and obese people. METHODS: A total of 33 schoolteachers without any self-reported voice alterations were invited to participate in this study. Participants were classified according to BMI into normal, overweight, and obese groups. The vocal loading task consisted of loud speech (60-90 minutes) in their classroom. Salivary and voice samples were taken before and after vocal loading. Perceptual and self-reported voice alterations and objective voice analyses were investigated. The relative concentration of salivary IL-6 was estimated by a colorimetric assay. RESULTS: Obese teachers showed a significant elevation in fundamental frequency value after vocal loading. In addition, reduction in harmonics-to-noise ratio (HNR) was observed in teachers with normal weight after vocal loading but not in overweight or obese groups. No significant correlation was observed between BMI and any of the acoustic parameters analyzed or salivary IL-6 levels. Furthermore, teachers who were overweight showed a significant increase in the salivary IL-6 levels after vocal loading. Interestingly, salivary IL-6 levels were positively correlated with HNR value in the overweight group after vocal loading. CONCLUSION: Excessive body weight is related to alterations in fundamental frequency and HNR. In addition, HNR, but not BMI, is associated with salivary IL-6 levels in overweight teachers.

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia.

To investigate whether fetal endothelial cell proliferation and migration are modulated by the A2A adenosine receptor (A2AAR), nitric oxide (NO) and the vascular endothelial growth factor (VEGF) signaling pathway, we isolated human umbilical vein endothelial cells from normal pregnancy (n = 23), preterm delivery (n = 4), and late-onset (LOPE, n = 10) and early-onset preeclampsia (EOPE, n = 8). We used the non-selective adenosine receptor agonist (NECA) and the selective agonist (CGS-21680) and/or selective antagonist (ZM-241385) for A2AAR. Also, the nitric oxide synthase (NOS) inhibitor, L-NAME, was used in co-incubation with CGS-21680. Compared to normal pregnancy, EOPE exhibited low cell proliferation and migration associated with reduced expressions of A2AAR and VEGF and NO synthesis (i.e., total and phosphorylated serine(1177) endothelial NOS and nitrite formation). In contrast, LOPE exhibited the opposite behavior in all these markers compared to normal pregnancy or EOPE. Cell proliferation and migration were increased by CGS-21680 (or NECA) in all analyzed groups (EOPE>LOPE>normal pregnancy) compared to their respective basal conditions, an effect that was associated with high NO and VEGF synthesis and blocked by ZM-241385 with significantly different IC50 for each group (EOPE>LOPE>normal pregnancy). The differences seem independent of gestational age. L-NAME blocked the CGS-21680-mediated cell proliferation and migration in normal pregnancy and LOPE (IC50 = 36.2 ± 2.5 and 8.6 ± 2.2 nM, respectively) as well as the VEGF expression in normal pregnancy. Therefore, the A2AAR/NO/VEGF signaling pathway exhibits a pro-angiogenic effect in normal pregnancies and LOPE, whereas impairment in this pathway seems related to the reduced angiogenic capacity of the fetal endothelium in EOPE.

Elevated concentrations of plasma adenosine in obese children.

There are no data regarding adenosine levels in obese children, even though is a ubiquitous molecule implicated in the regulation of lipid metabolism in humans. To determinate whether adenosine plasma levels are related with anthropometric and biochemical markers in children, we studied 51 students belong to Ramon Belmar School in Linares, Chile. Review of clinical data and frequent food questionnaire were taken in order to collect the information. Plasma adenosine levels were measured by high-performance liquid chromatography and biochemical parameters including insulin, glucose, total proteins, and lipid profile by using standard colorimetric assays. Children with detectable (above 0.1 µM) adenosine plasma levels (n = 30; BMI, 22.3 ± 0.7) had higher total cholesterol (P < 0.05); triglycerides (P < 0.01) and LDL-cholesterol (P < 0.05) concentrations than children with undetectable adenosine levels (n = 21; BMI, 23.9 ± 0.61). Among the analyzed variables, only BMI and BMI standard deviation score (BMI-SDS) were positively correlated with adenosine levels. Besides, obese children (n = 10) showed significantly high adenosine levels compared to controls (n = 11; 1.8 ± 0.2 vs. 1.2 ± 0.1 µM/mg protein, respectively. P < 0.05), but not compared to overweight children (n = 9). In conclusion, obesity in children is associated to high adenosine plasma levels. This study opens a new perspective to investigate the role of adenosine in the regulation of lipid metabolism in obese children.