Rodrigo Custodio

The emergence of the cortisol circadian rhythm in monozygotic and dizygotic twin infants : the twin-pair synchrony

Objective  Studies on the influence of genetic factors on the ontogeny of cortisol circadian rhythm in infants are lacking. This study evaluated the influence of twinning and the heritability on the age of emergence of salivary cortisol rhythm.

Measurement of salivary cortisol as a marker of stress in newborns in a neonatal intensive care unit.

Aims: The study was designed to evaluate the newborn (NB) stress response during the inpatient time in the neonatal intensive care unit. Methods: A quantitative, prospective, observational study was conducted with two NB groups. The first group consisted of 12 NB patients in the neonatal intensive care unit as the experimental group (EG), and the second included 43 NBs who were sent to their own homes and were considered the control group (CG). The EGs salivary cortisol concentration was measured on the 2nd day (D2) and 9th day (D9) of life. The CGs salivary cortisol concentration was measured on the 14th day of life at the childs own home. Results: The salivary cortisol concentration levels for the EG on D2 and D9 and for the CG were 4.3151 ± 2.6492, 1.826 ± 1.2252, and 1.0166 ± 0.8300 ng/dl, respectively. These findings indicated the presence of an adrenal response to stress during the first inpatient days. Conclusions: The salivary cortisol concentration is an accurate method to indicate neonatal stress. The glucocorticoids frequently used in the prenatal period suppress the adrenal glands and interfere with the stress response.

Fisiologia do eixo GH-sistema IGF

Growth, the main characteristic of childhood and adolescence, has a similar pattern in the majority of the individuals. Genetic background and GH-IGF axis are the factors that directly influence this process. Pituitary GH acts on growth mainly through the regulation of IGF system. The IGFs (IGF-1 and IGF-2) are growth factors produced in the majority of the organs and body tissues. They have autocrine, paracrine and endocrine actions on metabolism and cell proliferation, growth and differentiation. The IGFs bind with high specificity and affinity to a family of 6 binding proteins, called IGFBPs (1 to 6) that modulate their bioactivity. Most of the known IGF actions are mediated via IGF type 1 receptor (IGF1R). In this article we are going to review the composition and regulation of the GH-IGF axis and the role of each component in the regulation of the growth process.

Impact of hypoxia on IGF-I, IGF-II, IGFBP-3, ALS and IGFBP-1 regulation and on IGF1R gene expression in children

UNLABELLED Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans. OBJECTIVE The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children. DESIGN Twenty-seven previously health children (14 boys and 13 girls) aged 15 days to 9.5 years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test. RESULTS Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004, respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2(-ΔΔCT) was higher during HS than in NS (P=0.03). CONCLUSION The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process.

Localization of myosin-Va in subpopulations of cells in rat endocrine organs

Myosin-Va is a Ca2+/calmodulin-regulated unconventional myosin involved in the transport of vesicles, membranous organelles, and macromolecular complexes composed of proteins and mRNA. The cellular localization of myosin-Va has been described in great detail in several vertebrate cell types, including neurons, melanocytes, lymphocytes, auditory tissues, and a number of cultured cells. Here, we provide an immunohistochemical view of the tissue distribution of myosin-Va in the major endocrine organs. Myosin-Va is highly expressed in the pineal and pituitary glands and in specific cell populations of other endocrine glands, especially the parafollicular cells of the thyroid, the principal cells of the parathyroid, the islets of Langerhans of the pancreas, the chromaffin cells of the adrenal medulla, and a subpopulation of interstitial testicular cells. Weak to moderate staining has been detected in steroidogenic cells of the adrenal cortex, ovary, and Leydig cells. Myosin-Va has also been localized to non-endocrine cells, such as the germ cells of the seminiferous epithelium and maturing oocytes and in the intercalated ducts of the exocrine pancreas. These data provide the first systematic description of myosin-Va localization in the major endocrine organs of rat.

IGF-1R mRNA expression is increased in obese children

OBJECTIVES Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. METHODS Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls. Fasting blood samples were collected for IGF-IR mRNA expression in isolated lymphocytes and serum IGF-I, ALS, IGFBP-3, and IGFBP-1 concentration analysis. RESULTS Relative IGF-IR gene expression (2-ΔΔCT) was significantly (P=0.025) higher in obese children (median 1.87) than in controls (1.15). Fourteen of the 29 obese subjects showed 2-ΔΔCT values greater than or equal to 2, while only 2 individuals in the control group showed values above 2 (P=0.01). Obese children showed significantly (P=0.01) higher IGF-I concentrations than the control group (237ng/ml and 144ng/ml, respectively). Among obese patients, 65.5% had IGF-I values above the 75 percentile of the control group (P=0.02). ALS concentration was significantly (P=0.04) higher in the obese group, while IGFBP-3 levels were similar in obese and control children. IGFBP-1 concentration was lower in obese children, while insulin levels and HOMA-IR index were higher than in controls. CONCLUSIONS The higher IGF-IR mRNA expression observed in obese children, associated with the higher IGF-I and ALS and the lower IGFBP-1 levels, suggest that the higher stature observed in these children may be due to increased IGF-I bioactivity.

Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

Abstract Objective: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods: 40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Results: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. Conclusions: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy.

PO4-8: Subclinical hypothyroidism is associated with low IGF-I levels and decreased growth velocity

 Reduced serum IGF-I levels and GV were observed in children aged 4–36 months with SH. This was not found earlier in life.  These findings may reflect a direct action of thyroid hormones on IGF-I secretion rather than a modulation of GH action, as no changes were found on IGFBP-3 levels.  The real impact on height would demand a longer period of observation. Figure 1: Serum IGF-I and IGFBP-3 levels (Panel A) and GV-SDS (Panel B) in Groups IIA, IIB and IIC. Bars represent median (Panel A) or mean (Panel B).