ACTA ENDOCRINOLOGICA (BUC)

Objective. To assess in a bicentric study the current iodine status of schoolchildren, ten years after implementation of the universal salt iodization (USI) in Romania. Subjects and methods. 102 children from 2 towns, aged between 6 and 11 years, were included in the study group: 66 children from Sibiu, a previously endemic area for iodine deficiency disorders and 36 children from Bucharest, a previously borderline iodine intake area. Body mass index (BMI), total body surface area (BSA), median urinary iodine concentration (UIC) and prevalence of goiter were evaluated. Thyroid volume was measured by ultrasonography. The study was approved by the Local Ethics Committee. An informed consent from the parents was obtained. Results. From the 102 schoolchildren in the study group, 59 were girls and 43 were boys. Median UIC in the total number of samples was 175.2 mcg/L, reflecting a sufficient iodine intake, with statistically significant differences between the two urban regions. The median UIC was 187.35 mcg/L in the Sibiu subgroup and 160.2 mcg/L in the Bucharest subgroup (p < 0.001). The total percentage of goiter in the studied subjects was 5.88%. Percentage of goiter, determined by adjusting ultrasound thyroid volume to sex and BSA, was 1.51% in Sibiu and 13.88% in Bucharest, a statistically significant difference (p = 0.011). None of the subjects showed ultrasonographic pattern suggestive of Hashimoto thyroiditis or macronodules. There was no statistically significant difference between the percentages of overweight or obesity in the two subgroups. Conclusions. Ten years after implementation of USI in Romania, a bicentric study suggests that our country is iodine sufficient in urban areas. In order to prevent recurrence of mild iodine deficiency in schoolchildren, a persistent surveillance, use of sustainable measures and public awareness are required. Recurrence of mild iodine deficiency should be avoided, because even mild iodine deficiency impairs cognition in children.

Context. The inflammatory disorders of the urinary bladder represent one of the most frequent disorders associated with hormonal unbalances caused by menopause. The involvement of estrogens and mast cells in this complex mechanism mediated by neuro-hormonal pathway is well known, but the pathogenesis through which the hormonal deprivation is affecting the Estrogen Receptor expression and is predisposing to urinary bladder inflammatory changes is still argued. Objective. To determine the structural changes associated with surgically induced menopause, and the effect of estrogen replacement therapy (ERT) in the urinary bladder morphology, mast cell population and Estrogen Receptor (ERα) expression. Subjects and methods. The effect of ovariectomy and ERT was monitored by quantifying the number of mast cells and the structural changes that the urinary bladder suffers. By immunohistochemistry we assessed the changes of the Estrogen Receptor Alpha (ERα) expression in the urothelium and detrusor muscle. The study was carried out on ovariectomised female rats over a period of 42 days. Results. The main alterations associated with the hormonal deprivation were represented by the growth in number of the bladder mast cells, atrophy of the urothelium and amplification of the expression of ERα from the urothelium, but not from the detrusor muscle. ERT significantly decreased the tissue expression for ERα, reduced the severity of bladder atrophy and the number of mast cells. Conclusions. The estrogenic hormonal substitution can diminish the severity of the atrophic, inflammatory and ERα changes in bladder disorders associated with ovarectomy in rat.

Type 2 diabetes (T2D) increases the risk of coronary artery disease (CAD) in patients with type 2 diabetes compared with nondiabetic subjects. Several genetic variants are considered as risk factors for CAD, including those implicated in dyslipidaemia and oxidative stress. The PPARGC1A gene is considered as a key regulator of pathophysiological processes contributing to CAD. Aim. We investigated whether the Gly482Ser polymorphism (rs8192678) increased susceptibility to CAD in Iranian population and whether it was associated with clinical and metabolic parameters. Patients and methods. A total of 290 subjects including 149 CAD patients with a history of diabetes and 149 controls were included in our study. The Gly482Ser polymorphism was genotyped using ARMS-PCR method. Based on the type of variables, by the use of SPSS software (Statistical Package for Social Sciences Inc., Chicago, IL, USA) statistical analyses were performed. Results. We found a significant difference in the Gly482Ser substitution between the case and control subjects in Iranian population. However, no significant association was observed between Gly482Ser genotypes and physiologic variables. Conclusion. This gene polymorphism PPARGC1A Gly482Ser may be a potential marker for increased risk of CAD in diabetic patients in clinical treatment and diagnosis in clinical treatment and diagnosis in the Iranian population.

Purpose. The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods. This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results. Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR- 222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions. The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS.

Context. Hypoxic exposure has been associated with a metabolic perturbation that might affect basal energy expenditure (BEE). Objective. The aim was to examine the metabolic response during hypoxic exposure of men and women adults. Design. Crossover design with two experimental trials: normoxic and hypoxic exposure. Subjects and Methods. Twenty-nine healthy subjects (14 women) participated in (1) control study (NOR), subjected first to normoxic exposure (FiO2 = 20.9%) and (2) after that, to passive normobaric hypoxic exposure study (HYP) (FiO2 = 15%). Respiratory gases and blood glucose samples were recorded every hour in hypoxia chamber (8 points in total), and blood lactate samples were collected at baseline, at 4 and 7 h to exposure. Results. In females, basal energy expenditure was significantly higher at 2h, 4h, 6h and 7h compared with NOR group. Also, BEE was lower in females compared with men from 2h of hypoxia exposure. In the HYP group the blood lactate concentration increased significantly at 4h and 7 h relative to NOR group (P < 0.05) in males. Conclusion. An exposure to moderate normobaric hypoxia did not alter metabolic response, but induced a different response on substrate oxidation in adults men and women.

Objective. The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)- induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway. Methods. Total 21 paraffin-embedded testicular tissues of control (n=7), streptozotocin (STZ)-induced diabetic (n=7) and insulin-treated diabetic (n=7) Wistar albino rats were used in this study. Testicular damage was examined histologically and by Johnsen’s score was also evaluated. Immunohistochemical stainings of HGF and c-Met were analysed by using antibodies against HGF and c-Met. Results. We found the degeneration in seminiferous tubule epithelium and disorganization of spermatogenetic cell series in testis tissues of diabetic rats. We also determined decrease both in seminiferous tubule diameter and Johnsen’s scores in diabetic group. The expressions of HGF and c-Met in seminiferous tubule epithelium and in spermatogenic cells (especially spermatocytes and spermatids) were significantly increased in diabetic rats compared to those of control. Insulin treatment significantly reduced the diabetes-induced morphological changes and HGF/c-Met over expressions in the diabetic rat testis. Conclusion. HGF/c-Met pathway might have a role in diabetes- induced testicular damage. Drugs acting on this pathway might be effective to prevent or delay the testicular damage induced by diabetes.

Hypothalamic kisspeptin signaling has been recently observed to correlate with seasonal breeding in free ranging male rhesus monkeys. Recent evidence also suggests that excitatory and inhibitory amino acid neurotransmitters contribute in regulation of kisspeptin neurons. Objective. The present study was focused on analyzing the interplay of Kiss1 neurons with afferent excitatory and inhibitory signals in the brain of male rhesus monkeys during the breeding and non breeding seasons. We hypothesized that: kisspeptin stimulation may occur due to the increase in N-methyl-D,L-aspartate (NMDA) dependant excitatory inputs and decrease in inhibitory γ-aminobutyric acid (GABA) based cues during the breeding season Materials and Methods. Messenger ribonucleic acid (mRNA) was extracted from the medio basal hypothalamus (MBH) of five free ranging adult male rhesus monkeys (Macaca mulatta) during the breeding season (n=3; October; plasma testosterone levels: 26.15±2.64 nmol/L; testicular volume: 69.00 ± 0.57 ml); and the non-breeding season (n=2; July; plasma testosterone levels: 4.09±1.64 nmol/L; testicular volume: 12.88±0.31 ml). Real time polymerase chain reaction (RT-PCR) was used to quantify the levels of Kiss1, Kiss1r, NR1 and glutamic acid decarboxylase (GAD67) mRNA, relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results. Significantly high (p<0.05) expression of Kiss1, Kiss1r and NR1 mRNA and low (p<0.05) expression of GAD67 mRNA in the hypothalamus were found to be in synchrony with the breeding season. Conclusion. Based on correlative gene expression changes in the adult male monkey hypothalamus we suggest that in higher primates increased kisspeptin signaling during breeding season may be entrained by an increase in NMDA excitatory inputs; while decreased kisspeptin signaling during the non-breeding season may be driven by an increase in GABA based inhibitory cues.

Introduction. Diabetic chronic kidney disease has more fatal clinical progresses and this situation can be related to volume overload, which is seen more commonly in diabetic chronic kidney disease patients than in non-diabetic chronic kidney disease patients. Therefore, we examined the effect of diabetes mellitus on volume overload in newly diagnosed stage 5 chronic kidney disease patients whose volume overloads were not showing signs of improvement from renal replacement therapy. Method. One hundred and five patients (46 diabetic, 59 non-diabetic) with end-stage chronic kidney disease, who had glomerular filtration rate (GFR) under 15 mL/min for at least three months were enrolled in this prospective study. We determined the body volume overload and configuration using a bioimpedance device. NT-proBNP levels were recorded. Results. There was a statistically significant difference between diabetic and non-diabetic groups according to overhydration (OH, p=0.003), extracellular water (ECW, p=0.045), intracellular water (ICW, p<0.001) and OH/ECW (p=0.003). In addition, there was a statistically significant difference between groups in terms of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP levels, p=0.008). Discussion. We compared diabetic and nondiabetic end-stage chronic kidney disease patients who were not in renal replacement therapy yet. We found more volume overload and extracellular fluid volume in the diabetic group.

Introduction. Primary hyperparathyroidism is diagnosed earlier and more frequently with the introduction of routine serum calcium measurements. In literature, it is shown that mortality and morbidity decrease after parathyroidectomy. In our study, we aimed to determine the effect of parathyroidectomy on oxidative stress. Materials and Methods. The results of 41 patients who underwent parathyroidectomy for primary hyperparathyroidism between March 2018 and end of December 2018 were evaluated prospectively. Total antioxidant capacity (TAC), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), 8-hydroxy- 2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), parathyroid hormone, calcium and albumin were measured before and after parathyroidectomy. Results. The mean age of the patients in the study was 45 ± 13.1 years (age range: 18-76 years). The female/ male ratio was 32/9. Postoperative values of 8OHdG, MDA and SOD 1 were significantly lower than preoperative values (p <0.05). There was no significant difference between preoperative and postoperative TAC and TBARS values. Conclusion. Oxidative stress decreased in patients with primary hyperparathyroidism after parathyroidectomy. Randomized prospective studies are needed to show the relationship between biochemical and clinical parameters in order to see the clinical reflection of the study.

Context. Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. Material and Methods. Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Results. Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=- 0.359, p=0.007) was observed. Conclusion. Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.