Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay.

Objective: To analyze the GNRHR in patients with normosmic isolated hypogonadotropic hypogonadism (IHH) and constitutional delay of growth and puberty (CDGP).

Design: Molecular analysis and in vitro experiments correlated with phenotype.

Setting: Academic medical center.

Genetic predictors of long-term response to growth hormone (GH) therapy in children with GH deficiency and Turner syndrome: the influence of a SOCS2 polymorphism.

Background: There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling.

Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.

Background: Although chronic adrenocorticotropic hormone (ACTH) and androgen hyperstimulation are assumed to be involved in the pathogenesis of adrenal myelolipomas associated with poor-compliance patients with congenital adrenal hyperplasia (CAH), the expression of their receptors has not yet been demonstrated in these tumors so far.

Methods: We analyzed Melanocortin 2 receptor (MC2R), Androgen Receptor (AR), Leptin (LEP), and Steroidogenic factor 1 (SF1) expression using real-time qRT-PCR in two giant bilateral adrenal myelolipomas from two untreated simple virilizing CAH cases and in two sporadic adrenal myelolipomas. In addition, the X-chromosome inactivation pattern and CAG repeat numbers in AR exon 1 gene were evaluated in the 4 cases.

[Analysis of an iodide radioimmunoassay for 11-deoxicortisol measurement].

Objective: Our aim was to correlate 11-deoxycortisol levels obtained by two currently available techniques for 11-deoxycortisol measurement: radioimmunoassay, and high performance liquid chromatography followed by tandem mass spectrometry (MS/MS). The latter is the gold standard method for steroid hormone measurement.

Materials And Methods: We selected 88 samples and the results of these two methods were compared by Deming regression.

Clinical management of transsexual subjects.

Transsexual subjects are individuals who have a desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex, and a wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex. They seek to develop the physical characteristics of the desired gender, and should undergo an effective and safe treatment regimen. The goal of treatment is to rehabilitate the individual as a member of society in the gender he or she identifies with.

[Advances in the etiology, diagnosis and treatment of central precocious puberty].

The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys.

Long-term followup of a large cohort of patients with ovotesticular disorder of sex development.

Purpose: We present the followup of a large cohort of patients with ovotesticular disorder of sex development treated at a single tertiary center.

Materials And Methods: We reviewed the records of 20 patients with ovotesticular disorder of sex development. We retrospectively evaluated clinical and surgical characteristics.

Temporal genetic structure of major dengue vector Aedes aegypti from Manaus, Amazonas, Brazil.

In recent years, high levels of Aedes aegypti infestation and several dengue outbreaks with fatal outcome cases have been reported in Manaus, State of Amazonas, Brazil. This situation made it important to understand the genetic structure and gene flow patterns among the populations of this vector in Manaus, vital pieces of information for their management and development of new control strategies. In this study, we used nine microsatellite loci to examine the effect of seasonality on the genetic structure and gene flow patterns in Ae.

Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3.

Context: Loss-of-function mutations in makorin ring finger 3 (MKRN3), an imprinted gene located on the long arm of chromosome 15, have been recognized recently as a cause of familial central precocious puberty (CPP) in humans. MKRN3 has a potential inhibitory effect on GnRH secretion.

Objectives: The objective of the study was to investigate potential MKRN3 sequence variations as well as copy number and methylation abnormalities of the 15q11 locus in patients with apparently sporadic CPP.

Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome.

Objectives: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population.

Qualitative analysis of anatomopathological changes of gastric mucosa due to long term therapy with proton pump inhibitors: experimental studies x clinical studies.

Introduction: For a few decades the long-term use of proton pump inhibitors has had wide application in the treatment of several gastrointestinal diseases. Since then, however, several studies have called attention to the possible development of anatomical and pathological changes of gastric mucosa, resulting from the long term use of this therapeutic modality. Recent experimental and clinical studies suggest that these changes have connection not only to the development of precancerous lesions, but also of gastric tumors.

The sitting height/height ratio for age in healthy and short individuals and its potential role in selecting short children for SHOX analysis.

Aims: To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for SHOX analysis.

Methods: Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with SHOX defects (SHOX-D) and 193 females with Turner syndrome (TS).

Results: The frequency of abnormal body proportion, defined as SH/H SDS >2, in ISS children was 16.

Chromosomal location of retrotransposable REX 1 in the genomes in five (Teleostei: Characiformes.

Transposable elements are repetitive DNA sequences comprising a group of segments able to move and carry sequences within the genome. Studies involving comparative genomics have revealed that most vertebrates have different populations of transposable elements with significant differences among species of the same lineage. Few studies have been conducted in fish, the most diverse group of vertebrates, with the objective to locate different types of transposable elements.

Karyotypic conservatism in five species of Prochilodus (Characiformes, Prochilodontidae) disclosed by cytogenetic markers.

The family Prochilodontidae is considered a group with well conserved chromosomes characterized by their number, morphology and banding patterns. Thence, our study aimed at accomplishing a cytogenetic analysis with conventional methods (Giemsa staining, silver staining of the nucleolus organizer regions-AgNOR, and C-banding) and fluorescence in situ hybridization (FISH) with 18S and 5S ribosomal DNA probes in five species of the Prochilodus genus (Prochilodus argenteus, Prochilodus brevis, Prochilodus costatus, Prochilodus lineatus and Prochilodus nigricans) collected from different Brazilian hydrographic basins. The results revealed conservatism in chromosome number, morphology, AgNORs 18S and 5S rDNAs location and constitutive heterochromatin distribution patterns.

Molecular and gene network analysis of thyroid transcription factor 1 (TTF1) and enhanced at puberty (EAP1) genes in patients with GnRH-dependent pubertal disorders.

Background/aim: TTF1 and EAP1 are transcription factors that modulate gonadotropin-releasing hormone expression. We investigated the contribution of TTF1 and EAP1 genes to central pubertal disorders.

Patients And Methods: 133 patients with central pubertal disorders were studied: 86 with central precocious puberty and 47 with normosmic isolated hypogonadotropic hypogonadism.

Obesity and familial predisposition are significant determining factors of an adverse metabolic profile in young patients with congenital adrenal hyperplasia.

Background/aims: Glucocorticoid (GC) therapy is known to predispose to an adverse metabolic profile. Therefore, we investigated the prevalence of obesity and metabolic syndrome (MetS) in young patients with congenital adrenal hyperplasia (CAH) and to correlate this prevalence with GC treatment and family history.

Methods: The study population consisted of 33 young CAH patients who received cortisone acetate during their growth periods; those who were salt wasters also received fludrocortisone.

PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation.

Objective: The expression of transcription factors involved in early pituitary development, such as PROP1 and POU1F1, has been detected in pituitary adenoma tissues. In this study, we sought to characterize the transcriptional profiles of PROP1, POU1F1, and TBX19 in functioning and nonfunctioning pituitary adenomas in an attempt to identify their roles in tumorigenesis and hormone hypersecretion.

Methods: RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n=10), somatotrophinomas (n=8), and nonfunctioning adenomas (n=6).

Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age.

Objective: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth.

Patients And Methods: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively.

Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease.

Objectives: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease.

Late brain alterations in sepsis-survivor rats.

Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long-term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP).

Central precocious puberty caused by mutations in the imprinted gene MKRN3.

Background: The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Early activation of the hypothalamic-pituitary-gonadal axis results in central precocious puberty. The timing of pubertal development is driven in part by genetic factors, but only a few, rare molecular defects associated with central precocious puberty have been identified.

Combined use of multiplex ligation-dependent probe amplification and automatic sequencing for identification of KAL1 defects in patients with Kallmann syndrome.

Objective: To investigate the role of KAL1 abnormalities in Brazilian patients with Kallmann syndrome.

Design: In vitro experiments.

Setting: Academic medical center.

Unrecognized diabetes and myocardial necrosis: predictors of hyperglycemia in myocardial infarction.

Background: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood.

Objective: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis.