Eleni Kotanidou

Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells – an ultrastructural and immunohistochemical study

Summary Background Androgen abuse is an increasing problem amongst professional and amateur athletes. Moreover, testosterone, apart from its widely accepted indications, is used for a variety of other indications such as aging and ischemia. Its actions are mainly attributed to a specific genomic mechanism through the androgen receptor, but emerging evidence reveals non-genomic effects as well. The use of androgens has been linked with several adverse effects. The purpose of this study was to examine the effects of testosterone on the morphology and the ultrastructure of the myocardium and to investigate the possible role of apoptosis. Material/Methods We used 12 adult male Wistar rats, separated into 2 groups. Group A consisted of 6 rats that were administered high doses of testosterone enanthate, while group B consisted of 6 male Wistar rats that received placebo (normal saline) intramuscularly. After the last day of treatment, all rats were anesthetized and sacrificed, and the hearts were removed and processed for optical and electron microscopy and immunohistochemical detection of caspase-3, an apoptosis marker. Results We found significant myocardial hypertrophy along with abundant ultrastructural alterations. The immunohistochemical staining of the myocardial cells for caspase-3 was positive in group A (experimental group), which is interpreted as an activation of apoptosis by testosterone treatment. Conclusions Testosterone abuse has serious adverse effects, including myocardial hypertrophy, myocardial fibrosis and activation of apoptosis. These findings need to be taken into account whenever androgens are prescribed to improve performance or as hormone therapy.

Ten-year obesity and overweight prevalence in Greek children: a systematic review and meta-analysis of 2001-2010 data.

OBJECTIVE: While the US today has the highest rates worldwide of obesity, Europe, and particularly southern Europe, is catching up fast. The aim of this study was to report the prevalence of obesity in Greek children, aged 1–12 years. DESIGN: A systematic review—including all studies published in English and Greek from January 2001 until December 2010 regarding childhood obesity, using the IOTF criteria — was performed. Twenty-five out of 134 published studies were finally selected, including 219,996 boys and 210,772 girls. RESULTS: Meta-analysis revealed that 10.2% (CI 95%: 9.8–10.7%) of Greek children (1–12 years) are obese, 23.7% (CI 95%: 22.7–24.8%) are overweight and the combined prevalence of overweight and obesity is 34% (CI 95%: 32.7–35.3%). subgroup analysis by gender showed that 11% of the boys and 9.7% of the girls were obese, while 24.1% of the boys and 23.2% of the girls were overweight. The combined prevalence of excess in body weight predominated in boys (35%), while in girls the above prevalence was 32.7%. cumulative analysis revealed an upward trend of the phenomenon (2001–2003), followed by a stabilization (2003–2010). CONCLUSIONS: During the decade 2001–2010, 1/10 Greek children was obese and 3/10 were overweight. The implementation of policies to reverse childhood obesity is of the utmost urgency.

Apelin and G212A apelin receptor gene polymorphism in obese and diabese youth

The apelinergic system has been previously described to participate in fluid homeostasis, cardiac contractility, blood pressure and neo‐vascularization. The role of apelin in obesity and glucose metabolism has also lately gained interest; however, it still remains obscure. This study aimed to assess serum apelin levels in obese youngsters and to investigate any possible association with the G212A polymorphism of the apelin receptor (APLNR) gene.

Impaired glucose metabolism and bronchial hyperresponsiveness in obese prepubertal asthmatic children

Introduction: The prevalence of asthma and obesity has risen in parallel over the last decades, but the exact mechanisms linking these two diseases still remain unclear. The aim of the present study was to investigate the associations between bronchial hyperresponsiveness (BHR), impaired glucose metabolism, obesity, and asthma in prepubertal children. Methods: A total of 71 prepubertal children were included in the study and divided in four groups according to the presence of asthma and their Body Mass Index (BMI): Group 1‐Healthy Controls (HC), Group 2‐Non Obese Asthmatics (NOA), Group 3‐Obese Non Asthmatics (ONA), Group 4‐Obese Asthmatics (OA) Αll children underwent spirometry and bronchial hyperresponsiveness testing by using the cumulative Provoking Dose of mannitol (PD15, primary study variable); homeostasis model assessment‐estimated insulin resistance (HOMA‐IR) index was calculated in order to evaluate insulin resistance. Obese children also underwent an oral glucose tolerance testing (OGTT). Results: A statistically significant difference in bronchial hyperreactivity (mean ± SD) was detected in the group of obese asthmatic children who had lower values of PD15, (174.16 ± 126.42) as compared to normal weight asthmatic children (453.93 ± 110.27), (P < 0.001). Moreover, obese asthmatic children with confirmed insulin resistance (HOMA‐IR ≥2.5), had significantly lower PD15 values (89.05 ± 42.75) as compared to those with HOMA‐IR <2.5 (259.27 ± 125.75), (P = 0.006). Finally, obese asthmatic children with impaired OGTT had likewise significantly lower PD15 (81.02 ± 42.16) measurements as compared to children with normal OGTT (267.3 ± 112.62), (P = 0.001). Conclusion: Our findings suggest that obesity per se does not correlate to airway hyperreactivity unless it is accompanied by glucose intolerance and insulin resistance. Pediatr Pulmonol. 2017;52:160–166.

Suboptimal glycaemic control enhances the risk of impaired prothrombotic state in youths with type 1 diabetes mellitus

Objective: To estimate markers of prothrombotic state and endothelial dysfunction in youths with type 1 diabetes mellitus (T1DM) and investigate possible associations with anthropometric/demographic data, glycaemic control and lipid profile. Methods: In a cross-sectional design, we recruited 155 youths with T1DM and determined levels of plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids and glycosylated haemoglobin (HbA1c). Results: Of all the participants, 76 (49%) had increased levels of at least one of prothrombotic factors. Suboptimal glycaemic control was associated with a worse lipid profile and an eightfold increased risk of elevated vWF-Ag levels. Higher vWF-Ag concentrations were also correlated with impaired lipid profile and increased HbA1c values, whereas PAI-1-Ag was positively correlated only with triglyceride levels. After adjustment for potential confounders, only HbA1c contributed independently to the variation in vWF-Ag levels. Conclusion: Impaired prothrombotic state and consequently endothelial dysfunction are present in youths with T1DM, representing a cumulative risk factor for future cardiovascular disease (CVD). Achievement and maintenance of euglycaemia and normolipidaemia are crucial to decelerate progress of this process.

Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes

BackgroundThe association of selective immunoglobulin A (IgA) deficiency with type 1 diabetes (T1D) remains unclear. This study was to evaluate serum IgA concentrations in Greek children and adolescents with T1D.MethodsIn two hundred individuals with T1D, serum IgA concentrations were quantitatively determined using nephelometry.ResultsImmunoglobulin A deficiency was detected in 6 (3.0%) of 200 patients who were subjected to immunological evaluation. Recurrent infections were not recorded, but human papilloma virus infection was clinically suspected and confirmed by laboratory examination in a 5-year-old girl. In regard to coincidence of selective IgA deficiency with autoimmune diseases, celiac disease was detected in a girl and juvenile idiopathic arthritis in a boy. Serum IgA concentrations differed significantly when patients were grouped according to age at the beginning of the study (P<0.001), age at diagnosis of T1D (P=0.015) and coincidence of celiac disease (CD) (P=0.038). However, when the age of the patients was adjusted, difference in serum IgA concentrations was not statistically significant despite CD was present or not. Moreover, serum IgA concentrations were positively correlated with serum IgG (P<0.001) and IgE (P=0.001) concentrations and negatively correlated with serum antigliadin antibody IgG (P=0.035) concentrations. There was no association or correlation of serum IgA concentrations with glycemic control.ConclusionThe prevalence of selective IgA deficiency in Greek children and adolescents with T1D is high (3.0%). The correlation of serum IgA concentrations with serum IgG, IgE and anti-gliadin antibody IgG concentrations needs further investigation.

Secondary nocturnal enuresis related to central diabetes insipidus as an early manifestation of intracranial germinomatous germ cell tumors in a series of male youngsters

Nocturnal enuresis is a common symptom in children. It is usually attributed to benign causes and diagnostic evaluation is not carried out. We report three male young patients initially presenting with short stature and nocturnal enuresis, related to diabetes insipidus, caused by intracranial germinomatous germ cell tumors. In all three cases, water deprivation tests confirmed diabetes insipidus. Extensive endocrinological investigation also showed further hormone deficiencies. Magnetic resonance imaging of the brain revealed the presence of a central nervous system lesion and histology confirmed the final diagnosis. Surgery, radiation with or without chemotherapy was conducted and the patients were treated with hormone replacement therapies. The patients after a long follow-up were free of disease. We present these cases to alert clinicians to bear in mind that the presence of an intracranial germinomatous germ cell tumor should at least be considered in a child presenting with bed wetting, especially if additional symptoms and signs, including late onset puberty and growth delay or morning hypernatremia, may coexist.

A Novel Variant c.97C>T of the Growth Hormone Releasing Hormone Receptor Gene Causes Isolated Growth Hormone Deficiency Type Ib

Congenital isolated growth hormone deficiency (IGHD) type 1b is an autosomal recessive genetic condition caused by mutations of growth hormone (GH)-1 or the growth hormone releasing hormone receptor (GHRH-R) genes. Affected subjects present with symptoms of growth hormone deficiency (GHD) with low but detectable levels of growth hormone (GH), short stature and responsiveness to GH therapy. We describe a 13-month old girl with severe growth failure who showed a low GH response to two GH provocation tests and a modest increase of insulin-like growth factor-1 (IGF-1) to an IGF-1 generation test. Whole exome sequencing revealed a novel homozygous variant of the GHRH-R gene (c.97C>T), leading to a premature stop codon. Administration of recombinant human GH improved linear growth. This is the first report of a c.97C>T mutation of the GHRH-R gene.

l-selenomethionine supplementation in children and adolescents with autoimmune thyroiditis: A randomized double-blind placebo-controlled clinical trial

Although a beneficial effect of selenium (Se) administration has been proposed in adults with autoimmune thyroiditis (AT), there is a paucity of similar data in children and adolescents. The purpose of the study was to investigate whether administration of a high dose of organic Se (200 μg daily as l‐selenomethionine) has an effect on antithyroid antibody titres in children and adolescents with AT.

Osteoprotegerin increases parallel to insulin resistance in obese adolescents

ABSTRACT Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). Material and Methods: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. Results: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents’ subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. Conclusions: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.