Educational status, testosterone replacement, and intelligence outcomes in Klinefelter syndrome.

Most male hypergonadotropic hypogonadism associated with infertility can be attributed to a single genetic condition such as Klinefelter syndrome (KS). This disease's wide phenotypic variability is frequently associated with mosaic 47,XXY lineages and testosterone replacement. Early diagnosis and treatment have been associated with better cognitive and intellectual outcomes, but the scope of this influence requires further investigation. Objective: This study aimed to investigate the intelligence profile of a cohort of patients with KS, considering the influence of educational level and clinical variables. Methods: Twenty-nine (9-65 years) individuals were submitted to the measures of intelligence quotient (IQ) (Wechsler's Scales) and adaptive behavior (Vineland-II). Linear regression analysis included the participants' educational level and clinical variables (i.e., comorbidities and use of testosterone) as predictors and intellectual performance and adaptive behavior as outcomes. Results: Scores varied from intellectual deficiency to average ranges (82.5+15.8). There were significant differences between adult's and children's IQ and between verbal and nonverbal indexes. The level of education predicted both IQ and adaptive behavior. Testosterone replacement therapy and absence of seizures predicted only adaptive behavior. Conclusions: The level of education and hormonal therapy can be selectively implicated in the intellectual variability in KS.

A maioria dos casos de hipogonadismo hipergonadotrófico masculino associado à infertilidade pode ser atribuída a uma única condição genética ­ a síndrome de Klinefelter (KS). A ampla variabilidade fenotípica dessa doença está frequentemente associada a linhagens de mosaico 47,XXY e também à reposição de testosterona. O diagnóstico e o tratamento precoces têm sido associados a melhores desfechos em termos de cognição e inteligência, mas o escopo dessa influência requer maior investigação. Objetivo: Este estudo investigou o perfil de inteligência de uma coorte de pacientes com KS, considerando a influência do nível educacional e das variáveis clínicas. Métodos: Vinte e nove indivíduos (9­65 anos) foram submetidos a medidas de quociente de inteligência (escalas Wechsler) e de comportamento adaptativo (escala Vineland-II). A análise de regressão linear considerou o nível educacional dos participantes e variáveis clínicas (comorbidades, uso de testosterona) como preditores e desempenho intelectual e comportamento adaptativo como desfechos. Resultados: Os resultados mostraram escores que variaram de deficiência intelectual à faixa média (82,5+15,8). Houve diferenças significativas entre os quocientes de inteligência de adultos e crianças e entre os índices verbais e não verbais. O nível educacional influenciou tanto o quociente de inteligência quanto o comportamento adaptativo. A terapia de reposição de testosterona e a ausência de convulsões influenciaram apenas o comportamento adaptativo. . Conclusões: Sendo assim, nível educacional e terapia hormonal podem estar seletivamente implicados na variabilidade intelectual na KS.

Analyzing the toxicity of bisphenol-A to microalgae for ecotoxicological applications.

Bisphenol-A (BPA) is a chemical used in the production of polycarbonate plastic and epoxy resins that may be related to the occurrence of human endocrine disorders. The present study aims to indicate a microalgae for use in ecotoxicological tests concerning BPA contamination of aquatic environments by analyzing its toxicity for the freshwater species Pseudokirchneriella subcapitata, and the two marine species Tetraselmis chuii and Skeletonema costatum. The standardization of the test involved determination of suitable nominal concentrations of BPA and the most appropriate species for use as biomarkers. S. costatum and P. subcapitata demonstrated resistance to BPA, features that are not of interest for toxicity markers. T. chuii presented an adequate sensitivity to BPA, compatible with parameters used in human toxicology for this substance, and is indicated as a potential biomarker for the presence of BPA in marine environments. The IC50 of T. chuii was 2.5 µM with R2 = 0.9, indicating reliability to demonstrate that low concentrations of BPA has significant toxicity to this species.

Estrogen and Thyroid Hormone Receptor Activation by Medicinal Plants from Bahia, Brazil.

Background: A number of medicinal plants are traditionally used for metabolic disorders in Bahia state, Brazil. The aim of this study was to evaluate the estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts prepared from 20 plants. Methods: Species were extracted and assayed for receptor activation through both ER and TR gene-reporter assays, using 17ß-estradiol and triiodothyronine (T3), respectively, as the positive controls. Results: Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria verticillata (Rubiaceae) were able to activate ER as much as the positive control (17ß-estradiol). These three plant species were also assayed for TR activation. At the concentration of 50 µg/mL, C. cajans exerted the highest positive modulation on TR, causing an activation of 59.9%, while B. verticillata and A. cochliacarpus caused 30.8% and 23.3%, respectively. Conclusions: Our results contribute towards the validation of the traditional use of C. cajans, B. verticillata, and A. cochliacarpus in the treatment of metabolic disorders related to ER and TR functions. The gene-reporter assay was proven effective in screening crude plant extracts for ER/TR activation, endorsing this methodology as an important tool for future bioprospection studies focused on identifying novel starting molecules for the development of estrogen and thyroid agonists.

Anatomical specificity of the brain in the modulation of Neuroglobin and Cytoglobin genes after chronic bisphenol a exposure.

The aim of this study was to investigate the influence of Bisphenol A (BPA) exposure on Neuroglobin (Ngb) and Cytoglobin (Cygb) as well as oxidative stress gene expression in the cerebellum, hippocampus, hypothalamus and cortex. Male Wistar rats were randomly divided into 3 groups: Control and two groups receiving 2 different daily BPA dosages, 5 or 25 mg/kg from postnatal day 50 (PND50) through PND90 and they were euthanized at PND105. In the cortex, we found an increase in Ngb gene expression and also in superoxide dismutase 1 and Catalase (Cat). In the cerebellum, we found an increase in Ngb and Cat, in the hypothalamus, there was a decrease in Cygb and an increase in glutathione peroxidase and Cat and in hypoxia-inducible factor 1 alpha (Hif1α) at the low dosage and a decrease in Hif1α at the high BPA dosage. Finally, in the hippocampus, we observed a decrease in Ngb and Cygb and an increase in Hif1α. In summary, BPA promotes the modulation of both Ngb and Cygb, but such changes occur by different mechanisms depending on the exposure dose and anatomical area.

Molecular insights into the possible role of Kir4.1 and Kir5.1 in thyroid hormone biosynthesis.

INTRODUCTION: Thyroid morphogenesis is a complex process. Inwardly rectifying potassium (Kir) genes play a role in hormone release, cell excitability, pH and K(+) homeostasis in many tissues. OBJECTIVES: To investigate the thyroid developmental expression of three members, Kir4.1, Kir4.2 and Kir5.1, in mice. To postulate the K(+) channel role in thyroid hormone secretion. MATERIAL AND METHODS: Quantitative RT-PCR analysis of Kir4.1, Kir4.2 and Kir5.1 in mice of different stages (E13.5-E18.5). RESULTS: mRNA for Kir4.1, Kir4.2 and Kir5.1 were identified and increased with age in mice. Both Kir4.1 and Kir4.2 genes are better expressed after E16.5. Kir4.2 greatly increases from E13.5 to E16.5 (p ≤ 0.05). CONCLUSION: Quantitative PCR shows that the mouse thyroid presents increased expression for Kir channels during development. The role of Kir in thyroid morphogenesis and differentiation might be understood in future studies. We speculate that thyroglobulin trafficking might be modulated by Kir4.1/5.1.