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. 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.

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.

Background. Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, “neutrophilto- lymphocyte ratio” (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Material and methods. Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. Results. The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Conclusion. Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.

Objective. To characterize serum chemerin levels in obese patients with gestational diabetes mellitus (GDM). Design. Case–control study. Subjects and Methods. Forty seven obese women with newly diagnosed GDM at 24-28 weeks of pregnancy and 32 age, body mass index- and gestational age-matched, normal pregnant women were included. Metabolic patterns and serum chemerin concentrations were measured. Results. Serum chemerin levels were significantly higher in subjects with GDM as compared to healthy pregnant controls (p < 0.05). Fasting insulin was similar between the two groups. HOMA-IR tended to be higher in GDM group but did not reach statistical significance. Women with GDM had significantly higher triglyceride (p < 0.01) and lower highdensity lipoprotein cholesterol (p < 0.001) than controls. In multiple linear regression analyses, chemerin was significantly associated with BMI (beta-coefficient = 0.274, p = 0.01), HbA1c (beta-coefficient = 0.327, p < 0.01), HDL-cholesterol (beta-coefficient = -0.307, p < 0.01), triglyceride (betacoefficient = 0.236, p < 0.05), insulin levels (beta-coefficient = 0.236, p < 0.05) and HOMA index (beta-coefficient = 0.283, p = 0.01). Conclusions. Maternal chemerin levels were significantly increased in GDM at 24-28 weeks of pregnancy. The physiological significance of elevated serum chemerin in GDM remains unclear.

Context. Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective. The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods. Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results. In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/ mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion. Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

Cardiovascular disorders represented by congenital malformations, hypertension, aortic dilatation which can emerge in dissection or rupture and ischemic heart disease are common in Turner syndrome (TS) and life-threatening. Echocardiography and magnetic resonance imaging represent complementary diagnostic methods used to assess cardiovascular status. Unfortunately, normal reference ranges for cardiac and aortic measurements are established only in unselected TS patients, preventing a delineation between patients with and without cardiovascular pathology. We performed echocardiography in 15 patients with TS, aged 12-33 years (mean 21.8 years, standard deviation 6.37 years) without cardiovascular and renal malformations, hypertension or aortic dilatation and 30 normal controls; karyotype was 45,XO in 11 patients and 45,XO/46,XX in four patients. To minimize the influence of body size, ratios of aortic and cardiac chambers dimensions were calculated. As expected, we found smaller dimensions in TS versus controls but only the ascending aorta, left atrium and diastolic left ventricular diameters and the ratio diastolic / systolic left ventricular diameters reached statistical significance. Only aortic dimensions were entirely independent of age, height, weight and BMI with a 95% confidence interval of 14.28 &#8211; 25.32 (mean 19.8) mm for the aorta at the annulus and 95% CI 21.42 &#8211; 29.36 (mean 25.54) mm for the ascending aorta. The ratios ascending aorta/ systolic left ventricular diameter (95% confidence interval 0.54 &#8211; 1.34; mean 0.94), aorta at the annulus/systolic left ventricular diameter (95% CI 0.44 &#8211; 0.92; mean 0.68) and aorta at the annulus/ diastolic left ventricular diameter (95% CI 0.36 &#8211; 0.61; mean 0.49) are independent of age, height, weight and can also be reliable for detection of aortic dilatation.

Context: Vitamin D deficiency is extremely prevalent in nursing home residents and could be a risk factor for metabolic syndrome. Objective: To examine the association of serum vitamin D level with metabolic syndrome (MetS) in nursing home residents. Design: This was a case-control study. Subjects and Methods: We have investigated the status of vitamin D by measuring serum 25-hydroxyvitamin D (25OHD) concentrations in 45 older adults (28 women and 17 men, aged 58-89 years) living in a nursing-home in Iasi, Romania. Their vitamins D status (25-hydroxyvitamin D), C-reactive protein, fasting blood glucose, insulin, triglicerides, total and HDL cholesterol were assessed using venous blood. Systolic and diastolic blood pressure, weight, height and waist circumference were measured following standard protocols. Data was analysed using t-test, chi-square test, General Linear Model and multiple logistic regression. Results: In our study 56% of nursing home residents have serum 25(OH)D less than 30 nmol/l (vitamin D deficiency). Considering NCEP-ATP III criteria, the overall prevalence of the MetS in participants of this study was 35.5%. In the multivariate model (adjusted for sex, fasting serum glycemia, and triglycerides), vitamin D deficiency was significantly associated with being female (OR: 1.49; 95% CI: 0.38-5.73), abdominal obesity (OR: 1.34; 95% CI: 0.39-4.7), high systolic blood pressure (OR: 6.83; 95% CI: 1.09-42.9), low HDL-cholesterol (OR: 3.82; 95% CI: 0.55-26.6), and MetS (OR: 1.73; 95% CI: 0.27-10.8). Conclusions. This study highlights the high prevalence of vitamin D deficiency among nursing home residents and its association with multiple risk factors for metabolic syndrome.

Objective. To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). Study Design. Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. Results. Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18–166) and 51 IU (20–114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. Conclusion. T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.

Background. Early detection of coronary plaques in patients with diabetes mellitus (DM) could play a major role in improving the evolution of these patients, targeting a therapeutic intervention in early stages when the chances to reduce the progression of the disease are higher. Aim of the study was to evaluate the presence of coronary lesions and analyze the plaque morphology in patients with type 2 DM using multislice 64 computed tomography coronary angiography (MSCT), and to assess the cardiovascular risk expressed by calcium scoring (CS) in these patients. Methods. The study included 37 patients with type 2 DM. Mean age was 67.38 years (±19.62). In all cases MSCT was performed, CS was calculated and morphology of coronary plaques was analysed. Results. Coronary artery disease was present in 86.48% cases. CS was <100 in 6 patients (16.2%), between 100 and 400 in 7 patients (18.9%) and >400 in 24 cases (64.8%). Coronary plaques were classified as non-calcified in 142 segments, mixed in 78 segments and calcified in 114 segments. In 40.12% of lesions the plaques were nonobstructive, in 44.91% obstructive, and in 14.91% severely obstructive. Conclusions. In patients with type II DM there is a high incidence of coronary lesions and vascular calcification, which could represent an indicator of the severity of coronary artery disease even in asymptomatic diabetic patients. CS calculated with MSCT is increased in these patients, representing a marker of high cardiovascular risk.