ACTA ENDOCRINOLOGICA (BUC)

Introduction. Induction of heme oxygenase (HO) gene expression can protect lungs from Hypoxic Pulmonary\r\nVasoconstriction (HPV). Furthermore, there is evidence that Rho-kinase (ROCK) may be involved in HPV. Studies are going on to detect the real mechanisms involved in the phenomenon. Ghrelin, a 28-amino-acid peptide, has been shown that it may protect lungs from HPV side effects. The aim of this study was to evaluate the effect of exogenous ghrelin on HO and ROCK isoforms gene expression during chronic hypoxia (CH).\r\nMaterial and Method.Twenty four adult male Wistar rats were divided randomly in three groups. Hypoxic rats with saline or ghrelin treatment were placed in a normobaric hypoxic chamber (O2 11%), for two weeks. Controls remained in room air. HO and ROCK isoforms gene expression was measured by Real-Time RT-PCR. Lung tissues were histologically processed and stained with hematoxylin-eosin for morphometric analysis.\r\nResults. Morphometric analysis showed that ghrelin reversed the hypoxia induced pulmonary artery wall thickness (P < 0.001). In hypoxic animals, the amount of HO-1 expression increased but there was suppression in HO-2 gene expression (P < 0.05). Both ROCK-1 and ROCK-2 gene expressions were diminished after two-week hypoxia. Ghrelin treatment reduced the overexpression of HO-1 (P < 0.05), but had noeffect on ROCK gene expression.\r\nConclusion. Ghrelin by decreasing the expression of HO-1 and HO-2 in hypoxic animals may be involved in an adaptation\r\nmechanism during CH. However, ghrelin did not change ROCK isoforms gene expression, thus it could not affect HPV in this way. Nevertheless, more studies are needed to justify the protective roles of ghrelin for HPV.

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.

Aims. To test the effect of Hsa-miR-183-3p on cell aging and disc degeneration in lumbar intervertebral disc. Methods. This study combined clinical research with basic cell experiment, analyzing clinical data from patients with lumbar disc degeneration and traumatic lumbar spine fracture, as well as the differences in baseline data. The degree of lumbar disc injury in patients of different ages was also compared. Differentially expressed miRNAs were predicted via GEO database, and qPCR confirmation was determined by collecting cartilage endplates from two groups. ACAN, Col2A1, p16, p21, and p53 were detected by immunofluorescence, Western blot and qPCR in human nucleus pulposus cells. Changes of cell senescence were detected. The binding of Hsa-miR-183-3p to ataxiatelangiectasia mutated protein was confirmed by dual luciferase reporter assay. Results. Degenerative discs showed elevated expression of hsa-miR-183-3p, which may be upregulated by TNF-α via NF-κB signaling pathway and target ataxiatelangiectasia mutated protein regulation. Conclusion. Degeneration of the intervertebral disc can be accelerated by TNF-α. Additionally, Hsa-miR- 183-3p passed NF-κB signaling pathway is blocked via upregulation of TNF-α to reduce inflammation via targeting ataxia-telangiectasia mutated protein. As a result, this negative feedback mechanism may assist in maintaining a low degenerative load and preserving chronic disc degeneration.

Introduction. Vitamin D [25(OH)D] deficiency is prevalent in chronic kidney disease (CKD), related to bone turnover and potentially involved in arterial calcifications. Objective. To evaluate vitamin D status in nondialysis CKD patients and its relationships with bone turnover markers (BTM) and arterial calcifications. Design. Cross-sectional, prospective, multicentric study. Subjects and methods. One hundred twenty-eight CKD patients (median age 61 years, 58% males, median eGFR 29mL/min) were included. Comorbidities, mineral and bone metabolism parameters were evaluated. Total alkaline phosphatase (T-ALP) was used to assess bone turnover. Atherosclerosis was evaluated by carotid intima-media thickness (CIMT), endothelial calcifications by aortic calcification score (ACS), and arterial stiffness by cardio-ankle vascular index (CAVI). Vitamin D deficiency was defined as 25(OH)D <15 ng/mL. Factors associated with vitamin D, T-ALP and vascular parameters were assessed in multivariate regression models. Results. Prevalence of vitamin D deficiency was 63% and median 25(OH)D was 12.8 ng/mL. Older age, female sex and higher parathormone were predictors of vitamin D deficiency. Increased T-ALP was predicted by higher parathormone, suggesting high turnover bone disease. While age was a determinant of all evaluated vascular parameters, lower 25(OH)D was associated only with endothelial calcifications, which correlated with CAVI, suggesting a direct relation between vitamin D deficiency mediated plaques calcification and arterial stiffness. Conclusion. Vitamin D deficiency was highly prevalent in this non-dialysis CKD cohort and was related to age, sex and parathormone. Vitamin D deficiency was associated with increased calcifications of endothelial plaques, which seemed to increase arterial stiffness.

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.

Objective. Data about iodine status in pregnant women in Turkey is not sufficient. We aimed to determine the iodine status, goiter prevalence, iodized salt consumption among first trimester pregnant women living in Edirne. Design and Setting. Cross-sectional study was performed on pregnant women living in Edirne. Subjects and Methods. A total of 275 pregnant women in their first trimester were examined regarding iodized salt use, median urinary iodine concentration (UIC), presence or absence of goitre and thyroid function. Goitre status was determined by palpation. Participants filled out a questionnaire, which included questions regarding sociodemographic features, iodized salt consumption, knowledge, and behavior regarding iodine deficiency. UIC was measured using colorimetric method based on Sandell–Kolthoff reaction. Thyroid hormones and TSH were measured by chemiluminescence immunoassays. Results. While the proportion of iodized salt use was 96.6%, UIC was below 150 μg/L in 88.4 % of the women. The median UIC was 77 μg/L, indicating insufficient iodine intake. Total goitre rate was 19.3%. Conclusions. Our study shows that iodine deficiency is a serious problem among pregnant women in Edirne. We suggest that pregnant women living in Edirne should be supplemented by iodine-containing preparations in addition to iodized salt.

Context. Oxytocin has been investigated as a potential medication for psychiatric disorders. Objective and design. This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. Subjects and methods. Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, β-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. Results. Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). Conclusions. These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.

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.

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.

Objective. The existing studies involving omentin-1 have mainly focused on relationships with single cardiovascular risk factor. Whether omentin-1 is associated with the aggregation of cardiovascular risk factors has not been reported. We investigate the relationship between the serum omentin-1 level and aggregation of cardiovascular risk factors in adolescents. Subjects and Methods. A total of 741 young students, 11–16 years of age, were enrolled using a stratified cluster sampling method. The participants were given a questionnaire survey and underwent a physical examination. The aggregation of cardiovascular risk factors was defined as two or more cardiovascular risk factors occurring simultaneously in the same individual. Results. Partial correlation analysis suggested that serum omentin-1 level was significantly correlated with waist circumference (R=-0.086, P=0.019) and Body Mass Index (R=-0.096, P=0.009). Logistic regression analysis showed that as the serum omentin-1 level increased, the risk of aggregation of cardiovascular risk factors decreased. Cardiovascular risk factors which were most closely associated with a decrease in the serum omentin-1 level were obesity calculated by Body Mass Index (OR=0.988, P=0.043) and central obesity calculated by waist circumference (OR=0.993, P=0.012). Conclusions. The serum omentin-1 level in adolescents is inversely associated with the aggregation of cardiovascular risk factors. Waist circumference and Body Mass Index are factors most closely associated with a decrease in the serum omentin-1 level.