Germán Iñiguez

Objective: To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion). Design: This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption. Setting: This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile. Results: Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05). Conclusions: this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.

Introduction: Fetal growth restriction may be the consequence of maternal, fetal, or placental factors. The insulin-like growth factors (IGFs) are major determinants of fetal growth, and are expressed in the mother, fetus and placenta in most species. Previously we reported higher placental protein content of IGF-I, IGF-IR, and AKT in small (SGA) compared with those from appropriate for gestational age (AGA) placentas. The protein Klotho, has been reported in placenta and may regulate IGF-I activity. In this study we determined Klotho gene expression and protein immunostaining in term (T-SGA y T-AGA) and preterm (PT-SGA y PT-AGA) human placentas. In addition, we assessed the effect of Klotho on the IGF-IR and AKT activation induced by IGF-I.Methods: Placentas (n = 1 17) from 32 T-SGA (birth weight (BW) = −1.74 ± 0.08 SDS), 37 T-AGA (BW = 0.12 ± 0.12 SDS), 20 PT-SGA (BW = −2.08 ± 0.14 SDS), and 28 PT-AGA (BW = −0.43 ± 0.13 SDS) newborns were collected. mRNA expression by RT-PCR in the chorionic (CP) and basal (BP) plates of the placentas, and the presence of Klotho was evaluated by immunohistochemistry (integral optical density, IOD). In addition, we developed placental explants that were incubated with IGF-I in the presence or absence of Klotho.Results: We found a lower mRNA expression and protein immunoreactivity of Klotho in the CP of SGA (term and preterm) compared with AGA placentas. We also observed a significant reduction in IGF-IR tyrosine activation induced by IGF-I 10 nM when preincubated with 2.0 nM of Klotho (2.4 ± 0.5 arbitrary units vs. 1.3 ± 0.3 AU), and similar results we observed on AKT and ERK_42/44 activation.Conclusion: We describe for the first time that Klotho mRNA and protein varies according to fetal growth and gestational age. In addition, Klotho appears to down-regulate the activation induced by IGF-I on IGF-IR and AKT, suggesting that Klotho may be regulating IGF-I activity in human placentas according to intrauterine fetal growth.

The human placenta expresses the IGF-I and IGF-IR proteins and their intracellular signal components (IRS-1, AKT and mTOR). The aim of this study was to assess the IGF-IR content and activation of downstream signaling molecules in placentas from newborns who were classified by gestational age and birth weight. We studied placentas from 25 term appropriate (T-AGA), 26 term small (T-SGA), 22 preterm AGA (PT-AGA), and 20 preterm SGA (PT-SGA) newborns. The total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by Western Blot and normalized by actin or with their respective total content. The effect of IGF-I was determined by stimulating placental explants with recombinant IGF-I 10^-8 mol/L for 15, 30, and 60 minutes. The IGF-IR content was higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in PT-placentas compared with their respective T-placentas. The effect of IGF-I on the phosphorylated forms of IGF-IR was increased in T-SGA (150%) and PT-SGA (300%) compared with their respective AGA placentas. In addition, AKT serine phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90% and 390% respectively). The higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a compensatory mechanism in response to fetal growth restriction.

Prepubertal hypertrichosis is a reportedly benign condition characterized by an excessive growth of vellous hair in non-androgen dependent areas of the body compared to the amount usually present in normal subjects of the same age, race and sex. Although this condition is usually considered idiopathic and regarded as benign, it may be very disturbing cosmetically, causing significant patient and parental anxiety.

Artículo de publicación ISIAim: To compare pubertal development in age-matched healthy girls born with low birth weight (LBW) or appropriate birth weight for gestational age (AGA). Subjects and methods: Girls with breast in Tanner stage II and normal body mass index were followed for 3 years with a complete physical exam, bone age, pelvic ultrasound, and measurement of gonadal hormones using a leuprolide test. Results: Forty-one girls (AGA 25/LBW 16) were followed up for 3 years. By 3 years, they had similar bone age, adjusted height, and body composition. In LBW girls, breast Tanner stage advanced faster during the first 2 years of followup, which was associated with higher serum androgens. Hirsutism score, ovarian volume, and number of follicles between AGA and LBW were not different nor was age of menarche. By the third year, basal and poststimulated levels of gonadotropins and androgens anti-M ü llerian hormone and inhibin B were similar in both groups and did not show differences related to birth weight or degree of catch-up growth. Conclusion: LBW recruits showed a slightly faster breast development but no differences in androgen excess signs, internal genitalia, and gonadal hormonal patterns

Possible etiologies of idiopathic short stature (ISS) include a range of conditions, some of which may be caused by defects in the modulation of the growth hormone (GH)-signaling pathway. The Janus kinase/signal transducer and activator of transcription pathway is regulated by several mechanisms, including negative feedback regulation by the suppressors of cytokine signaling (SOCS). However, the specific induction of SOCS transcript levels in fibroblasts from ISS patients has not been studied. We determined the transcript levels of the SOCS1-3 genes under basal conditions, and in the presence or absence of stimulation with rhGH for 24 h in skin fibroblast cultures obtained from patients with ISS and children with normal height. Under basal conditions, ISS patients express higher SOCS2-3 transcript levels than control children. After incubation with recombinant human GH (rhGH), the transcript levels of SOCS2 increased significantly in ISS patients compared to controls (0.79 +/- 0.06 vs. 0.55 +/- 0.07; p = 0.03), a pattern which did not achieve statistical significance for SOCS3 transcript levels (0.55 +/- 0.08 vs. 0.40 +/- 0.07). The higher baseline transcript levels of the SOCS genes, and the increase observed for SOCS2 after rhGH treatment in ISS patients, suggest that growth retardation in some of these children may be mediated, at least in part, by intracellular overexpression of the SOCS genes.

Aromatase is the key enzyme for estrogen biosynthesis and is encoded by Cyp19 gene. In human placenta, Aro is expressed exclusively in syncytiotrophoblast. Alternative splicing of the coding region of Aro was previously described in other species but not in human. In male rat germ cells two unusual isoforms of Aro mRNAs lacking the last coding exon are expressed. In ovarian follicle of the fish Medaka, one of the two cDNAs described also lacks the sequence coding for the heme-binding domain. In rabbit preovulatory granulosa cells, a truncated Aro mRNAs is expressed. These findings suggest that alternative splicing events could be involved in the control of Aro expression. The aim of our study was to evaluate the expression of the IN9 variant (truncated mRNA lacking exon 10) in Pl. Total RNA was isolated from 15 Pl tissues from 6 males (m) and 9 females (f) newborn deliveries. Aro mRNA variant expression was analyzed by Real-time RT-PCR. Aro protein was analyzed by Western blot. We found expression of the IN9 variant in Pl. IN9 mRNA related to total Aro mRNA (CYP19) or active Aro mRNA (Arom) in m was significantly higher than in f (IN9/CYP19: 6.99±5.24 and IN9/Arom: 9.36±7.15 AU, mean±SD, n=6) (IN9/CYP19: 2.67±2.89 and IN9/Arom: 2.33±2.56 AU, mean±SD, n=11), p<0.05. We are describing for the first time a new Aro mRNA variant in human placenta that has a gender-specific expression. As the IN9 variant is a truncated Aro mRNA translating a non active protein, we propose that the expression of this variant would be involved in the regulation of Aro activity in human term placenta. Nothing to Disclose: RS, NS, GI, MAR, VM, AB

Fast growth in first 3 months of life adversely affects metabolic risks of young adults born at term.Controversy exists with regard to differences in metabolic risk in PT born SGA or AGA. Goal: To determine whether there are differences in BC, REE and metabolic variables between children born VLBW either AGA or SGA and whether these differences are related to a certain period of weight gain during the first year of life.67 VLBWPT(<32weeks /<1500g),(40AGA,27SGA). Followed as part of the National Program for VLBWPT infants from age 40 weeks until 7 yrs.BC by DEXA (Lunar DPX-L), REE by indirect calorimetry using the method Canopy (Deltatrac ®) and blood sampling at age 6.7±0.5 yr. Continuous variables: mean and SD and t Student test (independent groups). Categorical variables, frequencies and proportions compared by X2 (for independent groups). To assess the relationship of the different growth periods and body composition and energy expenditure: linear regression models with body composition and REE as dependent variables and the changes of weight SDS and length SDS as independents variables, were built. All these data were analyzed by a multivariate analysis.VLBWSGA children were leaner (p<0.05),shorter (p<0.01) and had lower waist and hip circumferences (p<0.005),HDL Chol(p<0.05) and higher % fat(p<0.05), % region of interest fat (ROI) (p<0.04), trunk fat (p<0.01) than their AGA counterpart (adjusted by age,sex,BMI).Weight gain patterns differed between SGA and AGA VLBW(p<0.001).The difference is observed by CA 0 and 3 months of life.After adjusting for age, gender and adequacy at birth (SGA/AGA) there was a direct correlation between weight gain in the first 3 months and total fat, % total fat, % ROI,% trunk fat and inversely with REE and FFM.Weight gain between 6-9 months in SGA was correlated with total and % fat mass and ROI whereas in AGA correlates only with REE and REE/fat free mass.Weight gain between 9 -12 months in SGA was correlated with total and % fat mass and trunk fat.By age 6 yr lower BW+higher fat mass subjects had higher Insulin and leptin(p<0.001).Summary:There were significant differences between SGA/AGA VLBW children in anthropometry, BC and calorimetry and these differences were correlated to early periods of growth.All periods of weight gain in SGA are correlated to fat mass whereas in AGA 6-9 months of weight gain are correlated with REE.We speculate that the difference in this period may be due to higher lean mass in AGA children. Sources of Research Support: Pfizer Individual Grant. Nothing to Disclose: CS, EP, CU, AA, GI, FC, VM

In humans, IGF-I and -II have an important role in pre- and postnatal growth. The IGFs circulate in plasma principally as a ternary complex with the IGF binding protein-3 and an acid-labile subunit (ALS), which increases their half life.

In humans, a direct relationship between IGF-I cord blood levels and birth weight has been demonstrated. To determine the placental IGF-I, IGF-II and IGF-IR mRNA and protein contents in full-term pregnancies from appropriate for gestational age (AGA), small for gestational age (SGA) and large for gestational age (LGA) newborns, we studied the placentas from 35 AGA, 30 SGA and 28 LGA pregnancies. The IGF-I, IGF-II and IGF-I receptor (IGF-IR) placental mRNA and protein contents were determined in the basal and chorionic plates of the placenta. IGF1 and IGF1R mRNA was higher in SGA compared to AGA and LGA placentas and lower in LGA compared with AGA placentas. In addition, a higher protein content of IGF-I and IGF-IR was observed in SGA compared with AGA and LGA placentas and lower contents in LGA compared with AGA placentas. These results suggest that the higher IGF-I and IGF-IR contents observed in SGA placentas and the lower contents observed in LGA placentas compared with AGA placentas may be influencing human fetal growth.