ACTA ENDOCRINOLOGICA (BUC)

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.

Context. The undercarboxylated form of osteocalcin (ucOC) and osteoprotegerin (OPG) are bonederived molecules involved in the endocrine crosstalk governing the bone, the adipose tissue and the pancreas. In addition, glucocorticoids are major determinants of both insulin resistance and osteoporosis. Objective. We aimed to investigate the response of ucOC and OPG to dysglycemia and/or dexamethasone (DXM) in primary human osteoblastic cell (HOC) cultures. Design and methods. Third-passage sub-confluent primary HOC cultures were treated with glucose: 2.8 mmol/L, 5.6 mmol/L, 11.1 mmol/L and 28 mmol/L, respectively. Alternatively, HOC cultures were subjected to DXM 1 μmol/L. In more complex experiments, HOC cultures were pre-treated with glucose (5.6 mmol/L) with/without insulin (1 pmol/L) followed by DXM (1 μmol/L). 24-hours posttreatment, culture medium ucOC and OPG were measured by ELISA. Results. ucOC production differed significantly (p<0.05) between cell groups, decreasing in a dosedependent manner as glucose concentration in the medium increased. Insulin prevented this effect. OPG levels appeared not to be significantly influenced by the hyperglycemic culture medium and were not related to ucOC concentration (p>0.05). Addition of DXM resulted in significantly lower ucOC concentrations compared to vehicle-treated cells (p<0.05). However, the effect of insulin co-treatment on ucOC was not counteracted by DXM (p<0.05). Conclusions. An obvious alteration of OC production/metabolism was observed as glucose levels changed in the bone microenvironment, to potentially be involved in diabetes-related osteopenia. DXM suppressed ucOC levels however not in insulin-rich environment.

Introduction. Adiponectin, resistin and osteoprotegerin (OPG) are cytokines expressed in the adipose tissue. Pregnancy is associated with gradually increased maternal\r\nlevels of these molecules, also detected in significant amounts in umbilical cord blood serum samples.\r\nAim, patients and methods. To establish the relationships of maternal and umbilical adiponectin, resistin and OPG levels to both maternal and fetal anthropometric measurements and insulin sensitivity, 28 mother-newborn pairs were enrolled in the study. Blood samples were collected in a fasting state, after delivery, and serum insulin, C-peptide, sex hormone-binding globulin, adipocytokines, OPG and bone specific alkaline phosphatase (BAP) were measured.\r\nResults. Compared to maternal values, umbilical serum adiponectin levels were about 3-fold higher; additionally, significantly higher resistin and lower OPG levels were\r\nobserved. Stratification of umbilical and maternal adiponectin levels according to tertiles of birth body weight demonstrated significantly lower maternal adiponectin\r\nlevels by tertiles of neonatal body weight. No relationships were noticed between infant birth weight and maternal or umbilical serum resistin and OPG, respectively. Umbilical resistin was significantly associated to both\r\nmaternal resistin and umbilical adiponectin. Multiple regression analysis showed that maternal BMI, umbilical insulin, C-peptide and resistin explained 71.83% of umbilical serum adiponectin variability. Umbilical resistin was independently predicted by umbilical adiponectin, umbilical C-peptide and maternal BMI, and the model explained 81.49% of umbilical resistin levels.\r\nConclusions. In human, umbilical serum adiponectin and resistin levels are significantly higher compared to adults. These adipokines may mediate the effects of maternal body mass on fetal development. The biology of the\r\nOPG/RANKL cytokine system in fetuses and newborns needs further research.

In this study we aimed to evaluate and quantify optic nerve damage caused by long standing compressive pituitary macroadenomas with conventional (ophthalmoscopy) and modern techniques such as fundus camera, confocal scanning laser tomography for quantitative measurements of the thickness of retinal layers as well as visual evoked potentials (VEP) for electrophysiological quantification. Seven patients with large, long standing pituitary macroadenomas were submitted to ophthalmologic evaluation, including a visual field (VF), visual acuity (VA) and eye fundus (F). Heidelberg retinal tomography (HRT) was used for retinal thickness and evaluation of nerve fibers loss, and VEP were measured by pattern reversal and flash stimulus. In addition, all patients underwent tumor imaging (MRI/CT) and specific endocrine evaluation. All cases presented with macroadenomas with suprasellar extension and residual or progressive optic chiasma syndrome; all but one (prolactinoma) were nonfunctioning adenomas, after radical treatment (surgery ? radiotherapy). Adrenal and thyroid substitutive treatment was instituted in all cases due to associated pituitary failure. Evaluation of VF showed 9 eyes with temporal hemianopia, 2 with nasal islands of vision and 1 with nasal hemianopia in a homonymous hemianopia case; another case presented for left 3rd nerve palsy due to a cavernous sinus syndrome, therefore the visual field was not measurable in 2 eyes. Visual acuity was very low (counting fingers) in 4 eyes, while in the rest the VA was between 0.5-0.9. The fundus revealed total atrophy in 2 eyes, band atrophy in 4, temporal pallor in 5 and global pallor in 1. Cup/disk ratio in the case with 3rd nerve palsy was 0.5 (RE) and 0.3 (LE). HRT II stereometric analysis of the optic nerve head showed abnormal values, documenting retinal nerve fiber layer (RNFL) loss that correlated with fundus appearance and visual field defects. Mean RNFL thickness had abnormal values in 8 eyes (from 0.074 to 0.173 &#956;m), correlated with RNFL cross sectional area in 7 eyes (from 0.362 to 0.846 &#956;m2) and 1 eye with low limit values (1000 &#956;m2). In agreement with these data, VEP&#8211;P100 presented increased latency over 120 ms in 8 eyes, borderline (100-120 ms) in 5 and 97.5 ms in only 1 eye. In conclusion, HRT can document the papilla and nerve fiber layer more objective, permitting quantification of the disc&#8217;s alterations due to compressive pituitary macroadenomas. HRT is useful in quantifying RNFL loss in other conditions than glaucoma, when other optic disc imaging tools are not available.

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.

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. 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.

Aim. The aim of this study is to present the personal experience of the authors regarding the use of positron emission tomography-computer tomography fusion image (PET/CT), with 18Ffluoro-2-deoxy-D-glucose (FDG), in the follow-up of differentiated thyroid carcinoma (DTC).\r\nPatients and Methods. Twenty seven cases of DTC admitted and treated in the &#8220;Prof. Ion Chiricu??&#8221; Institute of Oncology Cluj-Napoca (IOCN), performed PET/CT investigation\r\nbetween 2007 and 2009, in DOTE Centre Debrecen (Hungary) and Pozitron Center Oradea (Romania). The patients underwent the surgical intervention and had histology of differentiated carcinoma; they received radioiodine therapy with I-131, had suppression therapy with thyroid hormones and had in the follow-up whole body scans (WBS) with I-131, neck ultrasound and serological determination of thyroglobulin (Tg) and anti-thyroglobulin antibodies (anti-Tg). All patients were referred to PET/CT after radical treatment, after a negative WBS I-131 and a dynamic increase of the serological level of Tg or anti-Tg, without any clinical signs of\r\nrecurrence and no neck ultrasound pathological findings.\r\nResults. All patients included in this study presented abnormal levels of Tg: between 2.76 ng/ml and 4173 ng/ml, with a median value of 43.15 ng/ml. In 23 cases (85.1%) the PET/CT results revealed the neoplasm recurrence, in 3 cases we obtained true negative results and in 1 case a false negative image; in 2 cases (7.4%) we found a second malignancy. All patients needed to change the treatment strategies.\r\nConclusion. The significant increase of the number of DTC and the more aggressive behaviour of the disease in some situations, determines the existence of a clear strategy of\r\ntreatment and monitoring, where the role of PET/CT is well defined.