ACTA ENDOCRINOLOGICA (BUC)

Background. Following recent years, there is an increased body of literature on the connections that might exist between type 2 diabetes mellitus and the efficiency of bariatric surgery in its reversal compared to other medical approaches such as dieting. Aim. To induce experimentally type 2 diabetes mellitus in rats in order to observe the effects of bariatric surgery in the recovery as well as the reestablishment of normal insulin levels in order to extend the findings in house animals. Materials and methods. This study was conducted in three stages: the first consisted in inducing type 2 diabetes mellitus (T2DM) in 40 young Wistar male rats, by initially feeding them human food high in vegetal fats, oleaginous seeds, simple and complex carbohydrates, sugars, lipids, fats, proteins and fructose for a period of 8 weeks followed by a single low dose of streptozotocin (STZ), administered through intraperitoneal injection. The second stage of the study started when the rats became obese and therefore qualified for the bariatric procedure and the third stage consisted of post-operation supervision and care. The surgical procedure, performed on 10 obese rats, consisted in reducing the size of the stomach by partial gastrectomy of a 1.5 – 2.0 cm wide and 6.5 – 7.5 cm long area on the large curvature. Results. Showed rapid improvements in body weight and blood sugar control after 9 days. Conclusion. After putting the rats on a diet high in carbohydrates, sugars, lipids and fats and administering them STZ, the induction of type 2 diabetes was successful and the partial gastrectomy led to a better blood sugar control. The bariatric procedure provides a faster therapeutic response than conventional diets.

Context. The expression of TSHR-C on the serum tetraiodothyronine (T4) and TSH receptor antibody (TRAb) levels are rarely studied. Objective. The effect of TSHR-c on T4 and TRAb levels and concomitant thyroid histological changes in mice was investigated. Design. Animal experimental study. Subjects and methods. Female BALB/c mice at 6-8 weeks of age were immunized with the thyroid stimulating hormone receptor antigen C-terminus (TSHR-C), and randomly divided into control group (treated with the corresponding concentrations of normal saline) and four experimental subgroups: TSHR-c1 subgroup (4 μg), TSHR-c2 subgroup (6 μg), TSHR-c3 subgroup (8 μg) and TSHR-c4 subgroup (10 μg). Serum T4 and TRAb levels were determined. Results. The serum T4 level decreased significantly in the experimental mice as the concentration increased. All the experimental mice were positive for serum TRAb (experimental groups: 40 positive/40, 100% vs. control group: 3 positive/10, 30%) compared to the control group (P =0.000). HE staining showed that the follicles in the control mice were composed of small to medium-sized round follicles, whereas the follicles in the experimental mice were irregularly enlarged under light microscope. Conclusions. TSHR-c immunization resulted in thyroid hormone changes like those observed in hypothyroidism, probably due to the induction of TRAb generation.

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Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR- 149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA.

The effects of daily evening melatonin (MT) injections on plasma T3 and T4 and pineal thyroxin 5’-deiodinase (5’-D) activity in euthyroid and hypothyroid rats were investigated. Circulating levels of thyroid hormones were monitored and 5’-D activity was measured in pineal homogenates throughout the daily light-dark cycle. In the euthyroid group, T3 and T4 concentrations and pineal 5’-D activity gradually increased during the L-phase of the L/D cycle to reach maximum levels early at night. The lowest values for pineal 5’-D activity and T4 were obtained later at night when endogenous MT production was the highest. MT treatment induced an opposite circadian variation of plasma T3, T4 and pineal 5’-D activity with significant increases later at night and decreases early at night vs. the control group. In the hypothyroid group, the serum T4 and T3 concentrations significantly decreased at all moments assayed. Treatment with MT did not lead to significant changes in the propylthiouracil effect on T4 and T3 levels, but maintained the biphasic response, observed in the MT treated euthyroid group. The increases induced by PTU in pineal 5’-D activity during the light phase, were reduced from 43.61 ? 2.35 ng T3/mg protein / h to 33.36?2.87 ngT3/mg protein/h (p=0.01) by MT injections. In conclusion, the results rendered the presence of the 5’-D in the rat pineal, its activity showing a circadian pattern similar to the circulating T4 levels. The MT treatment induced an opposite circadian variation of serum T3, T4 and pineal 5’-D activity suggesting an interaction between the light/dark cycle, 5’-D activity and responsiveness to MT.

Context. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1–7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. Objective. We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. Design. We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. Results. MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). Patients with lower MDA (when divided according to median value of 3.88 nmol/ mL) had higher uACE2 57.15(40.3-71.2) pg/mL compared to 38.5(31.8-45.95) pg/mL in patients with higher MDA (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). Conclusion. Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.

Background. Warthin-like tumor of the thyroid (WALTT) is a very rare variant of papillary thyroid cancer.We want to draw attention to this rare condition by reporting two cases. Patient reports. Patient 1 was a 24 year-old woman presented with 14×12 mm solid nodule on the left lobe of the thyroid gland. Fine needle aspiration biopsy of the nodule was reported as suspicious for papillary thyroid carcinoma. Patient 2 was a 40 year-old woman who had multinodular thyroid gland with a 31×26 mm major nodule on the left lobe. On fine neddle aspiration, cytologic findings were consistent with papillary thyroid carcinoma. Both underwent total thyroidectomy and histological examination of the cases revealed Warthin-like tumor of the thyroid. Summary and conclusion. We report two patients with WALTT. This rare variant of papillary thyroid cancinoma has four main histologic criteria: papillary architecture, oxyphilic cytoplasmic changes, papillary nuclear features and dense lymphoid infiltrate. WALTT can be distinguished from other aggressive variants with these distinct histological features. Since variants show different clinical behaviour, classification of these might be helpful to predict patient prognosis.

Objective. Adrenal incidentaloma are lesions which are stated incidentally by imaging methods when there is no suspicion of any disease in adrenal gland. Inappropriate Jak2 signaling causes some solid and hematological malignancies. But the Jak2 mutation has not been previously evaluated with regard to adrenal tumors. In this study, we aimed to positivity of the Jak2 mutation in patients with non functioning adrenal incidentaloma (NFAI). Methods. 45 (38 female–7 male) patients, who were followed due to NFAI at Tepecik Training and Research Hospital, Department of Endocrinology and Internal Medicine between February 2014 and March 2015, and 45 (31 female–14 male) healthy controls were included in the study. Results. The average age was 54.02±11.7 years and 38 patients were female, 7 were men. All patients underwent the following analyses for excluding a functioning adrenal mass, overnight dexamethasone suppression test, 24 hour urinary metanephrine and normetanephrine, plasma aldosterone/ renin activity ratio. Jak2 mutation of the patients who were diagnosed as NFAI was all negative. Conclusion. We could not identify the JAK2 gene mutation positivity in any sample. Since other possible mechanisms may throw fresh light on the etiology of adrenal incidentaloma, further clinical studies are needed on this subject.