ACTA ENDOCRINOLOGICA (BUC)

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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.

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Objective. To assess iodine status (median urinary iodine concentration) in 118 pregnant women during the third trimester from endemic or non-endemic areas, a decade after implementation of Universal Salt Iodization in Romania. Subjects and methods. One hundred and eighteen pregnant women in the third trimester were included in the study group (age range: 16 – 46 years, mean age: 28.78 years). Median urinary iodine concentration (UIC) and body mass index (BMI) were evaluated. Data regarding region of provenance, smoking habits during pregnancy, education level, iodized salt intake, bread intake, iodine supplements, comorbidities (iron deficiency anemia) and birth weight were assessed. Morning urine was collected to measure median UIC. The study was approved by the Local Ethics Committee. Results. Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. There is a statistically significant difference between pregnant women with and without iodine supplements from rural areas (281.5 versus 196.1 mcg/L, respectively, p=0.023). In the subgroup without iodine supplementation, there was a significant difference between overweight and obese subjects vs. normal weight subjects (232.5 versus 194 mcg/L, p=0.012). Only in the subgroup with a daily intake of less than 5 slices of bread (usually containing iodized salt) we found significant differences between those with and without iodine supplements (245.2 versus 128.3 mcg/L). Iron deficiency anemia was found in 29.66% and 19.49% were current smokers during pregnancy. Conclusions. Median UIC in the study group was 206 mcg/L, reflecting iodine sufficiency during pregnancy. The difference between the subgroup with iodine supplements and the subgroup without iodine supplements was not statistically significant, probably due to the excessive consumption of bread and other bakery products which is traditional in Romania.

Obesity is a worldwide public health problem (both in developed and developing countries), the most frequent nutritional disease in the world, with considerable morbiditymortality and high costs for the public healthcare systems. Bariatric surgery has been found to be the only method capable of maintaining proper and long-lasting weight loss for morbid obesity. Laparoscopy is the gold standard for bariatric procedures. We studied a group of 341 patients who underwent different types of laparoscopic bariatric surgical procedures: laparoscopic adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), laparoscopic gastric bypass (LGB) and laparoscopic biliopancreatic diversion (LBPD). They were evaluated preoperative (weight, BMI, comorbidities) and followed-up for 1 year: 238 patients LAGB, 46 LSG, 49 LGB and 8 LBPD. Mortality and conversion rate were nil for all groups. A significant reduction in patients’ weight was shown at 12 months postoperatively. BMI decreased from 45.6 kg/m2 to 37.9 for LAGB, from 54.12 to 40.8 kg/m2 for LGB and from 49.1 to 31.2 kg/m2 for LSG. The excess weight loss for LBPD was 63%. A significant improvement of co-morbidities was noticed; all patients with type 2 diabetes have normal serum glucose levels at 1 year after surgery. Bariatric surgery is safe with a low complication rate and the outcome was similar to literature data. Although we do not benefit of a long time follow-up, the favorable results allow us to state that minimally invasive surgical techniques deserve an important place in the efforts of struggling against obesity and its consequences.

Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Background. The peroxisome proliferatoractivated receptor-γ co-activator 1-α (PPARGC1A), a key transcription factor involved in the control of metabolism and energy homeostasis, is an important biological and positional candidate of the metabolic syndrome. Association studies of its polymorphisms, however, yielded inconsistent sometimes conflicting results, pointing to important ethnic differences, which call for replication in various populations. Objective. In order to study its most common - potentially functional - polymorphism Gly482Ser (rs8192678), we carried out a case-control study in a central Romanian population. Material and methods. Two hundred and ninety six patients affected by the metabolic syndrome diagnosed according to the International Diabetes Federation proposed criteria and 166 middle-aged control subjects have been investigated. Genotyping was done by PCR-RFLP, using the restriction enzyme MspI. Results. While the G(Gly)/A(Ser) allele frequencies (66.89/33.11 vs. 71.68/28.31 %) and GG/GA/AA genotype distribution (45.27-43.24-11.48 vs. 54.21-34.93-10.84 %) differed in the metabolic syndrome and control group, the risk of developing the metabolic syndrome did not reach the limit of statistical significance (OR=1.43; p=0.06, CI 95%: 0.97-2.09). Metabolic parameters in the two study groups did not show significant differences according to the genotype (p>0.05). Conclusion. rs8192678 could be a functional polymorphism contributing to the development of the metabolic syndrome, but probably its effect is minor, and might depend on gene–gene and gene-environment interactions. Clarification of very small effects would require larger sample sizes.

Background. The occurrence of mixed dementia defined as the association of Alzheimer’s disease with vascular dementia is increasing due to the global aging of the human population. Since thyroid hormones play a role in cognition and alterations of the thyroid axis occur with aging it is reasonable to assume that thyroid function and cognitive decline in mixed dementia are linked. Objective. To investigate whether there is a link between TSH, oxidative stress, cognitive decline and depression in female patients with mixed dementia. Methods. Fourty female patients with mixed dementia and 10 healthy controls were included in the study. MMSE, depression score (Cornel Scale of depression), TSH, MDA, glutathione were determined. Serum TSH levels correlated with the cognitive decline measured by MMSE (r=0.55 p=0.0002) and with de depression score (r=0.34 p=0.0314). Furthermore an increase in the oxidative stress marker MDA (p=0.0004) and in the antioxidant defense marker Glutathione (p=0.0013) was observed in patients with mixed dementia. In addition the levels of Glutathione correlated with cognitive decline (r=-0.4997 p=0.001) and with the levels of TSH (r=-0.4997 p=0.001). Conclusion. Our results suggest that thyroid function, oxidative stress and mixed dementia are corelated. However, a possible cause and effect relationship is not yet proved.

The aim of this study was to examine the highglucose and high fatty acid status effect on the development of atherosclerosis. Materials and Methods. We used rat thoracic aorta smooth muscle cell line A7r5. We investigated mechanisms underlying high-glucose and high fatty acid (oleic acid) conditions on vascular smooth muscle cell (VSMC) mimicking concurrent status of diabetes and dyslipidemia. Results. Glucose-oleic acid stimulated cell proliferation and migration while the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 were activated. In addition, the expressions of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) enhanced by glucose-oleic acid were increased. The proliferation signal mediated by glucoseoleic acid condition was demonstrated via CTGF/FASN, while MMP-2 was regulated by CTGF but not FASN. Conclusion. Oleic acid in the presence of high glucose level can induce VSMC proliferation and migration leading to diabetes-associated vascular atherosclerosis. Furthermore, via activation of CTGF, increased expression of FASN suggested a possibility of lipogenesis in VSMC which may also contribute to diabetes-associated vascular atherosclerosis.

Background. Chronic inflammation is associated with different cancers, and is identified as a key pathogenic mechanism in ovarian cancer. The purpose of our study was to evaluate systemic inflammation markers, as predictive and prognostic factors, in ovarian cancer patients with initial surgical treatment. Subjects and Methods. We performed a retrospective study on 60 ovarian cancer patients with primary cytoreduction surgery, between 2010-2018, with a follow-up period of at least one year. We analyzed systemic inflammation markers and their correlations with the clinical, paraclinical, tumor characteristics, or treatment particularities, and evaluated them as prognostic factors for overall survival. Results. In the univariate analysis, no statistically significantly differences were observed, by correlating the systemic inflammation markers with age, reproductive status, FIGO stage, or type of cytoreduction. Higher neutrophillymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were statistically significant associated with deceased patients, and lower lymphocyte-monocyte ratio (LMR) had statistical significance for living patients. For the patients in the group, the increase of NLR, as well as of PLR leads to the increased risk of death, and the increase of LMR leads to the decrease of this risk. In the multivariate regression analysis, the increase of NLR determined an increased risk of death by 9.7%, and for LMR a reduced risk of death by 46.9%. Conclusions. Systemic inflammation markers had no statistical significance correlated with age, reproductive status, FIGO stage, serous cancer type, or type of cytoreduction but only with overall survival. NLR is an independent risk factor, while LMR is an independent protection factor as well as optimal cytoreduction.