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Performance-enhancing drugs (PEDs) gained wide popularity not only among sportsmen but also among specific subsets of population, such as adolescents. Apart from their claimed effects on athletic performance, they are very appealing due to the body shaping effect exerted on fat mass and fat-free mass. Besides the ‘‘underestimated’’ massive misuse of PEDs, the short- as well as long-term consequences of such habits remain largely unrecognized. They have been strictly associated with serious adverse effects, but molecular mechanisms are yet to be elucidated. Here, we analyze the current understanding of the molecular effects of supraphysiological doses of doping agents in healthy biological systems, at genomic and proteomic levels, in order to define the molecular sensors of organ/tissue impairment, determined by their misuse. The focus is put on the anabolic androgenic steroids (AASs), specifically testosterone (T) and its most potent derivative dihydrotestosterone (DHT), and on the peptide hormones, specifically the growth hormone (GH) and the insulin-like growth factor-1 (IGF-1). A map of molecular targets is defined and the risk incidence for human health is taken into account.

The aim of the study was to assess food consumption in a group of Roman adolescents in order to compare the energy and nutrient intakes with requirements.The authors have carried out a food survey on the whole scholastic population of two schools of Rome from 2003 to 2005. Nutritional status of students was assessed by measuring height, weight according to international indications. Food consumption was assessed by food records.Seventy hundred and seventy three subjects (773) 52% males, with an average age of 12.3 + or - 0.9 years were surveyed. The average daily intakes of fruit (128 g), vegetables (161 g), and legumes (12 g) were lower than recommended. The percentage of energy intake from fat (39%) and that from saturated fats (12%) were high. On the other hand, the percentage of energy intake from carbohydrates was low (46%) even if that from saturated fats (12%) was rather high. The students' diet was characterized by low intakes of fibre (16 g), calcium (815 mg) and iron (12 mg) in both males and females.Results indicate that the diet of these students is unbalanced in terms of macronutrients and deficient for some micro-nutrients, suggesting the need for nutrition education policy.

The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. Copyright 2010 Elsevier B.V. All rights reserved.

The present study examined the cardiovascular health effects of 16 weeks of recreational football training in untrained premenopausal women in comparison with continuous running training. Fifty healthy women were matched and randomized to a football (FG, n=25) or a running (RG, n=25) group and compared with a control group with no physical training (CO, n=15). Training was performed for 1 h twice a week. After 16 weeks, systolic and diastolic blood pressure was reduced (P

We performed a pilot study using human peripheral blood lymphocytes (PBL) as a novel system to identify new biomarkers of dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-1) abuse in sport. First, to obtain a gene signature, we treated cultures of lymphocytes from sedentary males with three doses of 0.237 microg/ml DHT, each of which is 80-fold the physiological concentration in young adult male serum, at days 0, 2 and 4, or with a single dose of 1.25 microg/ml IGF-1, which is 5-fold the physiological concentration in young adult male serum. We then used the Human Genome U133 Plus 2.0 microarray to identify a gene signature related to DHT or IGF-1 administration. Gene expression was evaluated after 7 and 21 days of DHT treatment, and after 24 h, 72 h and 7 days of IGF-1 treatment. Microarray analysis yielded a list of genes whose expression was altered after DHT or IGF-1 treatment. Among these we selected the genes that are most representative of the pathways associated with skeletal and muscular disorders using the IPA bioinformatics tool. We identified six (IDO1, CXCL13, CCL1, GZMB, VDR and IL2RA) and two (FN1 and RAB31) genes that were up-regulated in lymphocytes from sedentary subjects after 7 days of DHT and IGF-1 treatment, respectively. The expression of these genes in lymphocytes from differently trained athletes was either down-regulated or similar to that in lymphocytes from sedentary subjects. This finding suggests that up-regulation was due to the drug and not to physical exercise. In conclusion, we demonstrate that PBL can be useful in anti-doping checks, and we describe new biomarkers of DHT and IGF-1 abuse which can be included in the Athlete's Biological Passport.

The aim of this study was to investigate the prevalence of overweight/obese and hypertensive roman adolescents belonging to a medium-low social environment. The purpose of this research was also to find out the correlations between high blood pressure and obesity, dietary habits and physical activity.Nutritional status of 474 subjects (age 12.7+/-0.9 years) of a low-medium social class public school was assessed by measuring height, weight and waist circumference according to international indications. Over-weight and obesity were defined by body mass index (BMI) according to International Obesity Task Force (IOTF). Blood pressure (BP) was measured in duplicate and hypertension was defined by international percentiles. Food habits and lifestyle were investigated by a questionnaire. Multivariate logistic regression was used to relate variables.The prevalence of overweight and obese adolescents was respectively 31.7% and 10.3% with a slight higher presence of males in both cases. The whole sample showed a prevalence of hypertension of 10.1%. Systolic and diastolic BP showed a direct association with BMI and waist circumference (P0.01). BMI and systolic and diastolic BP were lower in active students (7 h a week of physical activity). Food habits were not associated with hypertension.The high prevalence of hypertensive adolescents could be explained with the consistent number of overweight/obese subjects, their social medium-low context and their being sedentary. As reported in literature, all these factors may contribute to the ''metabolic syndrome'' aetiology.

The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with the main electrophysiological and mechanical features of CMs. The key issue to be solved is to achieve a degree of structural and functional maturity typical of adult CMs. In this perspective, we will focus on the main differences between fetal-like hiPSC-CMs and adult CMs. A viewpoint is given on the different approaches used to improve hiPSC-CMs maturity, spanning from long-term culture to complex engineered heart tissue. Further, we outline limitations and future developments needed in cardiomyopathy disease modeling., Centro de Investigaciones Cardiovasculares

New competencies may be learned through active experience (experiential learning or learning by doing) or observation of others’ experiences (learning by observation). Observing another person performing a complex action facilitates the observer’s acquisition of the same action. The present research is aimed at analyzing if the observation of specific explorative strategies adopted in a constrained environment, such as the Radial Arm Maze (RAM), could help young children to explore the maze and to build a cognitive spatial map of the explored environment. To this aim young children were randomly assigned to three groups: children who performed the RAM task following the observation of an actor solving the same maze by putting into action a highly structured exploratory strategy; children who performed the RAM task following the observation of the actor solving the same maze by putting into action a less structured exploratory strategy; children who directly performed the RAM task without any observation. The main result of the present research is that the children who observed the highly structured and correct exploratory strategy spent less time, made fewer errors, exhibited a longer spatial span, and thus they explored the maze more efficiently than the children who directly performed the RAM task without any observation. This finding indicates that when the observed explorative procedure is structured, sequential and repetitive the action understanding and information storage processes are more effective. Importantly, the observation of specific spatial strategies helped the children to build the cognitive spatial map of the explored environment and consequently to acquire/enrich the declarative knowledge of the environment.

The melanocortin-4 receptor (MC4R) is involved in regulating energy homeostasis; mutations in this gene have been associated with 1-5% of early-onset human obesity. The aim of this study was to functionally characterize MC4R mutations identified in morbidly obese subjects living in Southern Italy. We studied their ligand binding, signaling pathway and subcellular localization. As expected, mutants Q43X and S19fsX51, which produce truncated forms of receptor, were devoid of activity. The activity of mutants W174C and A175T were very different even though the mutations are adjacent and are in the same transmembrane helix (TMH). In fact, the production and expression of mutant A175T on the plasma-membrane (PM) was similar to that of the wild-type (wt) receptor and the mutant retained 70% of wt receptor activity; on the contrary, the production of W174C mutant in the cytoplasm was similar to that of the wt receptor and mutant A175T but was only barely detectable on the PM and was devoid of activity. Confocal microscopy showed that W174C remained entrapped in the endoplasmic reticulum (ER) of the cells. Structural analysis showed that substitution of Trp174, located in the middle of TMH4 and 100% conserved in all known MC4Rs, with Cys could impair the relative orientation of TMH2 and TMH4 thereby affecting the overall protein architecture. Furthermore, co-expression studies showed that mutant A175T but not W174C had a dominant negative effect on the wt receptor activity. © 2010 Elsevier B.V.

Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and metabolic impairment in Caucasians. We investigated whether common variants in these genes are associated with metabolic syndrome (MetS) in a large group of morbidly obese young adults from southern Italy. One thousand morbidly obese subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years) whose families had lived in southern Italy for at least 2 generations were recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933 (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus) and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference were also determined. Binomial logistic regression showed that the TA heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore, the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together with total cholesterol, BMR and age. Our results extend the knowledge on genotype susceptibility for MetS in relation to a specific geographical area of residence.