ACTA ENDOCRINOLOGICA (BUC)

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3?-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on a subject of fundamental scientific interest.

The development of cancer in humans involves genetic and epigenetic changes that\r\nlead to cell cycle progression, inhibition of apoptosis, cell immortalisation, angiogenesis and\r\nthe ability to metastasise. One signalling pathway common to these events is the activation\r\nof phosphatidylinositol-3-kinase (PI3K) that affects downstream molecules involved in\r\nmalignant transformation. The article reviews the present data on the PI3K signalling, its\r\nderegulation in endocrine tumours, and new therapeutic strategies targeting this pathway in\r\nhuman neoplasia.

Aims. To provide growth references for school-aged children in western Romania, to compare them with other national and\r\ninternational growth charts and evaluate the prevalence of overweight and obesity.\r\nMethods. A total of 3731 children, aged 7-19 years, from Timis county, were examined by medical students, between\r\nFebruary 2010-June 2011. Growth references for height, weight, and body mass index (BMI) were constructed with LMS method and LMSChartMaker software. The Romanian 3rd, 50th and 95th percentile for height and BMI were compared with national and international growth references. The prevalence of overweight and obesity was determined with IOTF definition.\r\nResults. Crude and smoothed percentiles for weight, height and BMI were shown for this population. The comparison\r\nprovided data regarding the variation of growth models in different populations. Our results demonstrated a high prevalence of overweight (18.2%) and obesity (7.2%) in our\r\npopulation, higher in boys versus girls.\r\nConclusions. Our study constructed growth references for a Romanian population. The comparison with other growth references reflected the regional differences in growth\r\npatterns between populations.

Objectives. The aim of this study was to evaluate serum levels of interleukin (IL)-8 in pre- and postmenopausal women and in patients with surgically-induced menopause, and the relationship between IL-8 and vasomotor symptoms. Material and Method. 175 women were enrolled and were divided into 5 groups (I – Fertile women; II – Pre- and perimenopausal women; III – Postmenopausal women; IV – Surgically-induced menopause; V – Chronic inflammation). Multiplex cytokine kits were used to evaluate serum levels of interleukin-8. We determined the serum levels of the follicle stimulating hormone, of the luteinizing hormone, 17β-estradiol, progesterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate using sandwich ELISA. The severity of the vasomotor symptoms was evaluated according to FDA guidelines. Results. Serum concentration of IL-8 in women with natural menopause (233.0±226.5 pg/ml; p<0.001) and in women with surgically-induced menopause (148.0±162.0 pg/ml; p=0.045) is significantly higher than in women of reproductive age (84.88±82.32 pg/ml). Serum levels of IL-8 in premenopausal women, postmenopausal women, and in women with surgically-induced menopause, respectively, with severe and moderate hot flashes, on one hand (174.8±90.94 pg/ml, 369.3±194.2 pg/ml, respectively 274.1±146.3 pg/ml), is significantly higher than in women without vasomotor symptoms or with mild hot flashes, on the other hand (19.97±22.15 pg/ml, 28.66±35.72 pg/ml, respectively 28.94±37.68 pg/ml; p<0.001). Serum levels of IL-8 are significantly higher in women of reproductive age with chronic inflammatory pathology (152.3±121.0 pg/ml) than in women without such pathology (84.88±82.32 pg/ml; p=0.02). Conclusions. IL-8 is significantly higher in postmenopausal women with vasomotor symptoms than in women without vasomotor symptoms. In the postmenopausal group, the serum levels of IL-8 are similar to those in women with chronic inflammatory pathology. IL-8 could be a key factor in occurrence of hot flashes in menopause and could be associated with peripheral vasodilatation in these women.

Context. DEXA is recommended for osteoporosis screening. However, the rate of screening with DEXA is very low. Therefore, methods that can be used more easily and cost effectively are needed. Objective. The objective of this study is to develop a clinical risk assessment tool of osteoporosis (OSTEORISKAPP) by using syndromic approach. Design. A methodological study was performed. Subjects and Methods. Three hundred and fiftysix participants who are above 50 years old are participants of study and take history and physical examination. Positive likelihood ratio (LR), pre and post test probability, is calculated. A logistic regression analysis and a ROC analysis are made with the model constructed by those criteria. Results. Eighteen different clinical risk indices are diagnosed. According to LR, 4 of these criteria are minimally effective, 11 of them are weakly effective and 3 of them are medium effective criteria According to results of logistic regression analysis, back pain, waist pain, and usage of cortisone for more than 3 months, vertebra tenderness in physical examination, having dorsal kyphosis and being obese are turned out to be statistically significant in 89.9% confidence interval. AUC is found to be 0.948 and diagnostic test is found to have perfect distinction ability. Conclusion. Syndromic diagnostic criteria that will be used for osteoporosis screening of population and that is cost effective, no need to refer, practical, reliable and has tried to be developed.

Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). Objective. In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. Design, Subjects and Methods. This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. Results. Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. Conclusions. We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.

Background. Adiponectin, vaspin and leptin are only a few of these numerous adipocytokines. Little is known about the behavior of adipocytokines and how adipose tissue metabolism is affected in this Type 1 DM model. In this study we investigated the serum levels of adiponectin, leptin, vaspin in streptozotocin(STZ) induced diabetic rats. Material and methods. Twelve Spraque Dawley albino rats were included in the study. The animals were divided into two groups. The first group was diabetic (D) (n: 6) and 60mg / kg STZ was administered intraperitoneally (i.p.) to these rats. The second group was the non-diabetic control (ND) group (n: 6). All the animals were euthanized by cervical dislocation. Quantification of vaspin, Adiponectin, leptin in serum was performed using the ELISA kit. Results. Adiponectin, vaspin levels of diabetic group were found to be statistically lower than of control group (p<0.05). Leptin levels were significantly higher in the diabetic group (P<0.05). Conclusion. There is a need for new researches that can explain the relationship between Vaspin, Leptin and Adiponectin and Type 1 diabetes. New studies in this area will open new horizons for the identification of new biomarkers in the diagnosis and treatment of Type 1 diabetes.

Context. Coronary artery disease (CAD) is one of the common diseases in patients with type two diabetes mellitus (T2DM). The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPARγ) plays a vital role in dyslipidemia, and oxidative stress is involved in atherogenesis. Objective. The study aimed to determine the association between Pro12Ala polymorphism of the PPARγ2 gene(rs1801282) and CAD risk in T2DM patients in the Iranian population. Design. A group of 145 T2DM patients with a history of CAD were enrolled, together with 145 sex and gender-matched individuals who had neither CAD nor history of T2DM who were enrolled in a case-control study. Subjects and Methods. Polymerase chain reactionrestriction fragment length polymorphism technique was applied to genotype the PPARγ2 gene polymorphisms. Statistical analysis was done using SPSS version 22. Results. CC and GC genotypes of Pro12Ala had a higher frequency in the control and case groups, respectively. The GC genotype was associated with a significantly increased CAD risk compared to the CC genotype (adjusted OR= 2.66, 95% CI = 1.5-29.5, p<0.01). The mean triglycerides and total cholesterol level were significantly higher in the CC genotype than the GC genotype in both case and control groups (p<0.05). The mean level of fasting blood glucose was significantly higher in the CC genotype compared to GC genotype in the case group (p<0.05). The mean of creatinine, lipid profiles, microalbuminuria, and hemoglobin A1c had no significant difference between CC and GC genotypes in both groups (p>0.05). Conclusion. PPARγ2 Pro12Ala polymorphism could be an essential indicator for the increased risk of CAD in the Iranian people with T2DM.

Purpose. To determine the effectiveness of the basal calcitonin (CTb) determination in the early postoperative period to predict the possible recurrence (persistence) of medullary thyroid cancer (MTC). Material and Methods. A retrospective study of the treatment results in 194 patients with MTC (148 (76.3%) primary – group 1 and 46 (23.8%) recurrent – group 2) according to the levels of CTb in the first week after surgery and one year later. All groups were analyzed by staging, the level of preoperative and postoperative basal calcitonin 5 days and 1 year after the primary surgery. Findings. Among all patients, women prevailed – 144 (74.2%), the average age was (48.7±15.2), the average follow-up period was 67.5 months. Basal calcitonin was studied in patients of all groups in the preoperative and serially in the postoperative periods: 5 days and 1 year after the most radical surgical volumes. To test the hypothesis about the possibility of using CTb indicators in the early postoperative period, the degree of compliance with normal calcitonin indicators (≤18 pg/mL) was assessed by observation groups 5 days and 1 year after surgery. Conclusions. 1. The CTb value 5 days after surgery is no less a reliable marker of the result of surgical treatment of MTC than the currently recommended CTb measurement 2-3 months after surgery. 2. The technique is applicable for both primary and reoperations used for recurrent forms of medullary thyroid cancer.

Objectives. The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.- 280G>T) polymorphisms and endometriosis in Romanian women. Material and methods. We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results. There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.- 280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions. FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.