ACTA ENDOCRINOLOGICA (BUC)

Introduction. KCNJ11 gene activating mutations play a major role in the development of neonatal diabetes mellitus (NDM). KCNJ 11 gene encodes the Kir 6.2 subunit of ATP- sensitive potassium channel which is a critical regulator of pancreatic beta-cell insulin secretion. Aim. To study KCNJ11 gene mutations in infants with NDM and the effect of sulfonylurea treatment on the glycemic control in patients with KCNJ11 gene mutation. Subjects and methods. Thirty infants with NDM were screened for KCNJ11 gene mutations by DNA sequencing, insulin therapy was replaced by sulfonylurea treatment in patients with mutations. Results. R201C heterozygous mutation was found in one patient who was successfully shifted from insulin therapy to sulfonylurea treatment, while E23k, I337V, and S385C polymorphisms were detected in 14 patients. Conclusion. Screening for KCNJ 11 gene mutations could lead to identification of patients with mutations who can be successfully shifted from insulin therapy to sulfonylurea treatment improving their quality of life.

Objective. Endoplasmic reticulum stress (ERS) is suspected as an important factor in the initiation of insulin resistance. Aim. To explore the effects of exendin-4 (Ex- 4) on the endoplasmic reticulum stress (ERS)-mediated insulin resistance in 3T3-L1 adipocytes. In our study, 3T3-L1 adipocytes were pre-treated with ERS inhibitors tauroursodeoxycholic acid (TUDCA), Ex-4 and an ERS inducer tunicamycin (TM) then induced insulin resistance. Glucose consumption of the adipocytes was measured. Western blots determined the protein levels of ERS markers and insulin signaling pathway. Results. TM treatment reduced insulin-stimulated glucose consumption by 19.7% in 3T3-L1 adipocytes. This repression was blunted by 24h pre-treatment with TUDCA or Ex-4. Ex-4 augmented insulin-stimulated glucose consumption in adipocytes by 14.9%. Western blotting showed that TM treatment significantly increased the ER stress markers including p-IRE, p-JNK, p-PERK, p-eIF2a and ATF6 expression, whereas 24h pre-treatment of adipocytes with TUDCA or Ex-4 alleviated the ER stress. Ex-4 alleviates ERS-induced insulin resistance by upregulating the expression of phosphorylated Akt. Conclusion. ERs mediates insulin resistance in 3T3-L1 adipocytes, and exendin-4 significantly improves this insulin resistance.

Context. Hashimoto’s thyroiditis is the most common autoimmune disorder as cause of secondary hypothyroidism. The disease is associated with several metabolic disturbances and inflammatory disorders. Objectives. The aim of the current report was to evaluate several inflammatory and metabolic predictors of Hashimoto’s thyroiditis. Subjects and Methods. In the current study, forty patients with Hashimoto’s thyroiditis participated in the current study. They were aged between 20 to 50 years old. Anthropometric and nutritional measurements were assessed and biochemical factors including serum VEGF, IL-23, Nesfatin-1 and serum lipids were measured. Results. Waist circumference was higher among patients with lower serum TSH concentrations. Serum HDL and T4 concentrations were lower and serum IL-23 was higher among patients with higher TSH concentrations. BMI, WC and serum HDL were negative predictors of serum TSH while IL-23 was positively associated with TSH concentrations. Serum lipids including TC, TG and LDL were also negatively associated with T3 and T4 concentrations. Conclusions. According to our findings, VEGF and serum IL-23 were potent predictors of Hashimoto’s thyroiditis. However, further studies are warranted to better clarify these associations and underlying pathologic mechanisms.

Background. In the Carpathian area of Romania the Iodine Deficiency Disorders (IDD) including endemic goiter are a public health problem. Recently, the legislation imposing salt iodization was strengthened (from 10 to 20 ± 5 mg iodine/kg salt) and enlarged (universal salt iodization, USI, has been applied to bread industry since 2002). Objective. The effect of bread iodization by law upon the characteristics of goiter endemy was assessed in Arges county, Romania. Design. The characteristics of goiter endemy (as defined by WHO/ICCIDD/UNICEF) were determined in children in the years 1999 (control group C) and 2004 (study group S), two years after universal bread iodization. In the control group C there were 1,241 schoolchildren 6-14 years old, living in 5 villages and in Pitesti town. In the study group S there were 408 schoolchildren 6-12 years old, living in 7 villages and in Pitesti town. After universal bread iodization, a neonatal screening for hypothyroidism was also performed on 11,216 newborns in Arges county, between January 2003 and December 2004. The content of KIO3 in the salt was assessed both in samples collected from village shops in the years 1999 (10 samples) and 2004 (17 samples). The iodine content of drinking water in Arges county villages was assessed in 1999. Methods. Three parameters of IDD endemy were evaluated, i.e. the thyroid volume in schoolchildren by palpation or/and ultrasonography, urinary iodine by the Sandell-Kolthoff method, and neonatal blood TSH levels in dry spot by immunoassay. A questionnaire was filled in by 912 schoolchildren in 1999 and by 408 schoolchildren in 2004.

Context. In the year 2003-2004 a circumstantial investigation of young men reproductive health parameters was performed in Nordic and Baltic countries, but sexuality remained undetermined. Objective. To determine the suitability of the European Male Ageing Study – Sexual Function Questionnaire (EMAS – SFQ) for investigation of sexuality of 26–36 year aged general population and to investigate sexuality of Kaunas participants in the project “The reproductive function of Estonian, Latvian and Lithuanian Young men (2003-2004)” (KELLY), using EMAS – SFQ. Design. Sixty one 26–36 year aged KELLY men were recaptured from the list of participants in a 2003-2004 study and completed EMAS – SFQ. Their anthropometric characteristics, scores of sexuality (22 parameters from EMAS – SFQ, 3 calculated parameters and 2 parameters consisting from answers to the only question - masturbation and erectile function-for each participant) were analysed, in conjunction with anthropometric, sperm quality and hormone levels of 2003-2004 18–25 year old general population. Results. Overall sexual functioning and masturbation were higher as compared to all the published data for different age men and different testosterone concentration groups of EMAS study. Conclusions. KELLY sexuality results, obtained using EMAS – SFQ, would be considered as referral values for young men in countries with generally good reproductive health.

Aims: we wanted to check the importance of sunlight exposure and vitamin D supplementation in reverting secondary hyperparathyroidism at IIIrd age institutionalized patients.\r\nDesign: cross-sectional study of calcium and bone metabolism in a group of 123 institutionalized IIIrd age volunteers after winter period, followed by a prospective double blind placebo-controlled study of effects upon calcium and bone metabolism, serum 25OHD3, 1,25(OH)2D3 and PTH levels of daily sunlight exposure during the summer months, with or without vitamin D supplementation (2000 IU 25OH-D3 po, daily). The study was performed on volunteers from the Elderly Resting House of Copou,\r\nIasi, Romania. 25OH-D3 was measured by an inhouse RIA technique. 1,25(OH)2D3 was measured by HPLC, serum calcium by photocolorimetry, bone alkaline phosphatase by immunoenzymatic technique, whereas serum PTH and urinary deoxypyridinoline (DPD) were measured by IRMA. Data was compared using Student&#8217;s t test and correlation analysis (R2). Almost all volunteers (93.5%) had low 25OH-D3 values, but normal or even increased levels of the active hormone, 1,25(OH)2D3. High PTH was found in 41 cases (33.3%), of which three were primary hyperparathyroidism, whereas the others had low or low-normal calcium levels (secondary hyperparathyroidism). More than half of the cases had high DPD levels, suggesting high bone turnover. Bone turnover parameters were higher in females than in males (p<0.05). A positive correlation between PTH and urinary DPD was noticed (R2=0.351). We further supplemented the vitamin D intake in 42 volunteers with a daily dose of 2000 IU of 25-OHD3 for three months in the summer period, whereas other 42 volunteers received placebo (vitamin B). Normalization of 25-OHD3 levels was seen in both vitamin D and placebo-treated sun-exposed groups. A more significant increase in 25OHD3, and also of 1,25(OH)2D3 at the upper limit of normal was however observed in the vitamin D-treated group. Normalization of serum PTH, but not of turnover parameters was observed in both groups. Mild hypercalcemia and increase in serum creatinine were noticed in the vitamin D-treated group.\r\nConclusions: Secondary hyperparathyroidism might be of importance in high turnover bone loss at institutionalized IIIrd age patients. Women seem to be more at risk, possibly due to sex hormone depletion. PTH-induced 1&#945; hydroxylation in the elderly with undamaged kidney function partially compensates the paucity of vitamin D substrate, by normalizing active hormone levels. Mild sun exposure at institutionalized patients increases skin resources of vitamin D, normalizing 25OH-D3 levels and reverting secondary hyperparathyroidism. Oral vitamin D supplementation added to sunlight exposure should be done with caution, since it might be accompanied in certain patients by hypercalcemic or nephrotoxic effects at doses higher than 2000 IU/day.

Background. Osteoporosis has a high incidence after menopause, and at the same time the relationship between menopausal oestrogen deprivation and proinflammatory status is considered to be involved in postmenopausal bone turnover. Objective. The aim of this study was to evaluate the serum levels of IL-1β and of the TNFα in pre and postmenopausal women, as well as to investigate the relationship between these cytokines and bone mineral density. Design. A case-control study was performed during a period of 12 months. Subjects and Methods. The study included 150 women divided into 4 study groups. Serum levels of IL-1β and TNFα were determined using multiplex cytokine kits. BMD was measured by DXA at the level of the hip and lumbar spine. Results. Serum concentration of IL-1β is significantly higher in natural and surgically induced menopausal women, compared to women in the control group. Serum levels of TNFα in postmenopausal women and with surgically induced menopause are significantly higher than in fertile and premenopausal women. Serum levels of IL-1β are significantly higher in patients with osteopenia and osteoporosis compared to patients with normal BMD values. We found a negative correlation between serum levels of IL-1β, TNFα and BMD in pre and postmenopausal women, and in women with surgically induced menopause. Conclusions. Serum levels of IL- 1β and TNFα are significantly higher in menopausal women compared to fertile women. IL-1β is significantly higher in patients with osteopenia and osteoporosis than in women with normal BMD values, and IL-1β and TNFα associate negatively with BMD in pre and postmenopausal women, as well as in women with surgically induced menopause.

Objective. Medical Nutrition Therapy (MNT) is important in the treatment and regulation of diabetic patients. In this study, it was aimed to evaluate the effects of medical nutrition therapy on Pentraxin-3, hsCRP and body composition analysis in Type 2 diabetes patients (DM). Methods. This study included 160 individuals who were admitted and diagnosed with Type 2 DM. Laboratory, clinical, anthropometric and body composition parameters were obtained 3 months after baseline evaluation of the patients and the MNT was given by the dietitian. Results. After 3 months MNT, weight, body mass index, waist circumference, body fat weight, body fat ratio and visceral fat area (p<0.001), glucose (p<0.001), insulin (p=0.033), HOMA index (p=0.004), HbA1c (p<0.001), total cholesterol (p=0.001), LDL (p=0.008), ALT (p<0.001) and hsCRP (p<0.001) levels were significantly lower than they were before MNT. There wasn’t significant difference in triglyceride (p=0.509), HDL (p=0.079), Pentraxin-3 (p=0.706) levels and waist-to-hip ratio (p=0.802). The level of Framingham risk score after MNT was significantly lower (p<0.001). Conclusion. In this study, it was cocluded that MNT, applied to patients with Type 2 DM decreased cardiovascular risk and inflammation, contributed to the maintenance of glycemic control, and a significantly improved the body composition.

Background. Lithium, a well known antimanic drug, has adverse effects on endocrine functions; but it is unknown in aged animals.\r\nAim. Untoward effects of lithium on thyroidal and extra-thyroidal thyroid hormones were investigated in adult and aged rats.\r\nMaterials and methods. Lithium was injected intraperitoneally at a dose of 2 mEq/kg\r\nbody weight daily to one group of rats for 10 days and the other for 25 days respectively. Thyroid and serum T3 and T4, and extrathyroidal liver and kidney T3and T4 levels were\r\nmeasured by ELISA. Pituitary and serum TSH-like substance was determined using a human-TSH immunoassay kit. Thyroperoxidase profile was measured spectrophotometrically.\r\nResults. Lithium decreased thyroid and serum T3 and T4 levels, and increased pituitary and serum TSH-like profiles after 10 and 25 days of treatments respectively in adult and aged rats. Thyroperoxidase activity was decreased in all the treatments of adult and aged rats. Liver\r\nand kidney T3 and T4 profiles were also decreased in lithium recipients. Lithium actions were severe after 10 days of treatment in adult rats and 25 days treatment in aged rats.\r\nConclusion. Lithium has untoward effects on thyroid and extra-thyroidal thyroid hormone synthesis irrespective of the age of rats.

Objective. Cardiovascular disorders in diabetes condition arise from increased oxidative stress. Both regular mild exercise and testosterone influence on body’s antioxidant system in diabetes. In this study, we evaluated treatment of testosterone and voluntary exercise, alone or together on oxidative stress in the heart and blood of diabetic rats. Methods. Type 1 diabetes was induced by intraperitoneal injection of 50 mg/kg of streptozotocin in rats. Sixty three rats have been divided into eight groups as follows: Diabetes, diabetes+ testosterone, diabetes+ exercise, diabetes+ testosterone+ exercise, diabetes+ castration, diabetes+ castration+ testosterone, Diabetes+ castration+ exercise, Diabetes+ castration+ exercise+ testosterone. Type 1 diabetes was induced by intraperitoneal injection of 50 mg/ kg of streptozotocin in the male Wistar rats and after a week, castration was performed. After 42 days of treatment with testosterone (2 mg/kg/day) or voluntary exercise alone or in combination, SOD, GPX and CAT activities and MDA levels were measured in the blood and heart tissue samples in the groups of study. In the end of study, SOD, GPX and CAT activities and MDA levels were measured in blood and heart tissue samples in the groups of study. Results. SOD, GPX and CAT activities significantly (p<0.05) increased in groups that treated either testosterone or exercise and MDA level significantly (p<0.01) decreased in the blood and heart tissue of diabetic and castrated diabetic rats. Simultaneously, treatment with testosterone and exercise had a synergistic effect on antioxidant enzymes level in diabetic and diabetic castrated rats. In the castrated animals with diabetes, SOD, GPX and CAT activities significantly decreased (p<0.05) and MDA levels significantly increased (p<0.05) in blood and heart tissue. Conclusion. Voluntary exercise and testosterone alone or together heightened body’s antioxidant system and were able to reduce the MDA levels in blood and heart of diabetic and castrated diabetic rats.