Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera. These results were phenocopied in endothelial cells cultured in a medium containing high concentrations of glucose, which activates inducible nitric oxide synthase with a consequent increase of nitric oxide. Inhibition of the enzyme prevented high glucose-induced hyperpermeability, thus pointing to nitric oxide as the mediator involved in altering the endothelial barrier function. Since nitric oxide is much higher in sera from hyperglycaemic than normoglycaemic T1D patients, and the inhibition of inducible nitric oxide synthase prevents sera-dependent increased endothelial permeability, this enzyme might represent a promising biochemical marker to be monitored in T1D patients to predict alterations of the vascular wall, eventually promoting intimal lipid accumulation

Is Macronutrients Intake a Challenge for Cardiometabolic Risk in Obese Adolescents?

(1) Background: Pediatric obesity is an emerging public health issue, mainly related to western diet. A cross-sectional study was conducted to explore the association between macronutrients intake and cardiometabolic risk factors in obese adolescents. (2) Methods: Ninety-three Italian obese adolescents were recruited; anthropometric parameters, body composition, glucose and lipid metabolism profiles were measured. Macronutrients intake was estimated by a software-assisted analysis of a 120-item frequency questionnaire. The association between macronutrients and cardiometabolic risk factors was assessed by bivariate correlation, and multiple regression analysis was used to adjust for confounders such as age and sex. (3) Results: By multiple regression analysis, we found that higher energy and lower carbohydrate intakes predicted higher body mass index (BMI) z-score, p = 0.005, and higher saturated fats intake and higher age predicted higher HOmeostasis Model Assessment of insulin resistance (HOMA-IR) and lower QUantitative Insulin-sensitivity ChecK (QUICK) index, p = 0.001. In addition, a saturated fats intake <7% was associated with normal HOMA-IR, and a higher total fats intake predicted a higher HOMA of percent \u3b2-cell function (HOMA-\u3b2), p = 0.011. (4) Conclusions: Higher energy intake and lower carbohydrate dietary intake predicted higher BMI z-score after adjustment for age and sex. Higher total and saturated fats dietary intakes predicted insulin resistance, even after adjustment for confounding factors. A dietary pattern including appropriate high-quality carbohydrate and reduced saturated fat intakes could result in reduced cardiometabolic risk in obese adolescents

Use of Soy-Based Formulas and Cow's Milk Allergy: Lights and Shadows.

oybean (Glycine max) is a species of legume native to East Asia and used in childhood diet for over 2,000 years in the East. Soy protein formulas have been available for almost a century. Nowadays, the increase in cow's milk allergy and vegetarian dietary preferences are driving consumers toward cow's milk alternatives. In this paper, we reviewed the nutritional composition of soy-based infant formula and discussed their possible use in pediatric age, mainly focusing on prevention and treatment of cow's milk allergy. Protein quality is determined by digestibility and amino acid content. Purified or concentrated vegetable proteins (e.g., soy protein and gluten) have high digestibility (>95%), similar to those of animal ones. For some intact vegetable products (e.g., whole cereals and pulses), protein digestibility is lower (80-90%). Food processing and heat treatment also influence protein digestibility. Considering these data, we tried to evaluate the possible use of soybean and derivatives in pediatric age, including the nutritional composition of soy formulas and the clinical indications for their use. Moreover, since plant-based beverages are being perceived as healthy by consumers and their use is growing on the market, we recommend that soy drink should not be used as a substitute for infant formulas or cow's milk in children younger than 24 months

The role of fetal, infant, and childhood nutrition in the timing of sexual maturation

Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity

EXPOsure : Milan, May 1st-October 31st

The city of Milan is experiencing the great event of EXPO 2015 and heavy construction has been ongoing since 2012 over an area of more than 1 million meters squared in the north-west suburban area of the city. We compared the number of hospital admissions for upper and lower respiratory tract infections (URTI and LRTI) and acute asthma, in infants and children aged between 0 and 13 years from 2011 to 2014 in two Pediatric Departments, one near and one far from the EXPO construction area. Hospital admission frequencies resulted to be similar in the two Pediatric Departments

A New Selective PPARγ Modulator Inhibits Triglycerides Accumulation during Murine Adipocytes’ and Human Adipose-Derived Mesenchymal Stem Cells Differentiation

Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor \u3b3 (PPAR\u3b3) modulator, during adipose differentiation of murine pre-adipocytes and human Adipose Derived Stem Cells (hADSCs). We differentiated 3T3-L1 cells and primary hADSCs in the presence of various doses of GMG-43AC and evaluated the differentiation efficiency measuring lipid accumulation, the expression of specific differentiation markers and the quantification of accumulated triglycerides. The treatment with GMG-43AC is not toxic as shown by cell viability assessments after the treatments. Our findings demonstrate the inhibition of lipid accumulation and the significant decrease in the expression of adipocyte-specific genes, such as PPAR\u3b3, FABP-4, and leptin. This effect was long lasting, as the removal of GMG-43AC from culture medium did not allow the restoration of adipogenic process. The above actions were confirmed in hADSCs exposed to adipogenic stimuli. Together, these results indicate that GMG-43AC efficiently inhibits adipocytes differentiation in murine and human cells, suggesting its possible function in the reversal of adipogenesis and modulation of lipolysis

Potential role of omega-3 polyunsaturated fatty acids in pediatric food allergy

Polyunsaturated fatty acids (PUFAs) are involved both in immune system regulation and inflammation. In particular, within the PUFAs category, omega-3 (ω-3) may reduce inflammation, whereas omega-6 (ω-6) PUFAs are generally considered to have a proinflammatory effect. Recent evidence highlights an imbalance in the ω-3: ω-6 ratio with an increased intake of ω-6, as a consequence of the shift towards a westernized diet. In critical age groups such as infants, toddlers and young children, as well as pregnant and lactating women or fish allergic patients, ω-3 intake may be inadequate. This review aims to discuss the potential beneficial effects of PUFAs on pediatric food allergy prevention and treatment, both at prenatal and postnatal ages. Data from preclinical studies with PUFAs supplementation show encouraging effects in suppressing allergic response. Clinical studies results are still conflicting about the best timing and dosages of supplementation and which individuals are most likely to benefit; therefore, it is still not possible to draw firm conclusions. With regard to food-allergic children, it is still debated whether PUFAs could slow disease progression or not, since consistent data are lacking. In conclusion, more data on the effects of ω-3 PUFAs supplementation alone or in combination with other nutrients are warranted, both in the general and food allergic population

Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study

The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity