ACTA ENDOCRINOLOGICA (BUC)

Thyroid hormones play a crucial role in the regulation of the mitochondrial oxidative\r\nmetabolism. Hyperthyroidism caused by the acceleration of the energy metabolism leads to\r\nthe occurrence of cellular oxidative stress.\r\nThe aim is to evaluate the pro-oxidant / antioxidant balance and the effect of vitamin\r\nE supplementation in damage caused by the excessive administration of thyroid hormones.\r\nMaterials and Methods. White, male Wistar rats were used in the study. Thirty male\r\nWistar rats were divided into three groups (1:control group, 2:animals treated with LThyroxine\r\n10 &#956;g/animal/day for 30 days, 3:L-Thyroxin treated rats protected with vitamin\r\nE 10 mg/animal/day). Malondialdehyde (MDA), the marker of lipid peroxidation, carbonyl\r\nproteins, SH groups, glutathione (GSH) and superoxide dismutase (SOD) were determined\r\nfrom the serum, while MDA, carbonyl proteins, SH groups and GSH were determined from\r\nthe thyroid tissue homogenates.\r\nThe results showed increased levels of carbonyl proteins (1.31?0.33 nmol/mg protein,\r\np=0.0001) in serum in thyrotoxic group versus control, while MDA levels did not differ\r\nsignificantly from the control. Significantly low values of the SH groups, GSH and SOD were\r\nfound (p<0.001) in the plasma of Thyroxin treated rats. Vitamin E supplementation\r\nsignificantly increased plasma MDA levels in the Thyroxin treated group as compared with\r\nthe control group (p=0.01) and with the animals treated only with Thyroxin (p=0.04).\r\nCarbonyl protein levels in plasma of the hyperthyroid supplemented rats were also increased\r\nas compared to controls (p=0.0002). Antioxidant capacity markers in plasma of group 3 were\r\ndecreased compared with group 1. The marker of lipid peroxidation (MDA) significantly\r\ndecreased in thyroid homogenates of the group 2 as compared with group 1 (p=0.004).\r\nSignificantly high levels of the SH groups (p=0.0006) and low levels of GSH (p=0.0001) were\r\nfound in thyroid homogenates of the L-Thyroxin treated group as compared with controls.\r\nThese results suggest that experimental hyperthyroidism is accompanied with\r\nincreased oxidative stress and with the consumption of antioxidant enzymes in induced\r\noxidative aggressions. No protective effects of vitamin E on oxidative stress induced by\r\nexcessive administration of thyroid hormones were detected.

Gastrointestinal complaints are common among diabetic patients. The gastrointestinal tract contains melatonin. The binding sites of melatonin have been identified in all GIT tissues. Melatonin can modify activities of the gut and liver. The aim of this study was to evaluate the possible protective effects of melatonin against gastric motility and secretary responses in Streptozotocin-induced diabetes in rats. Methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. One week after inducing diabetes, Melatonin (5, 10, 20 mg/ kg/day, IP.) was injected for 14 days. Gastric acid and mucus were measured in all animals by chemical methods. Gastric motility was investigated by powerlab system. Results. Streptozotocin induced a significant increase in blood glucose levels (p<0.001) and significant decrease in gastric acid, mucus, motility and body weight in diabetic groups. Treatment of diabetic rats with melatonin significantly reduced blood glucose (p<0.001) and increased gastric mucus (p<0.001) and motility (p<0.01 and p<0.05 in groups 4 and 5 respectively) with no effect on body weight and gastric acid concentration. Conclusion. These data suggested that melatonin treatment has a therapeutic effect on diabetic gastrointestinal disturbances by reduction of serum glucose and increasing gastric motility and gastric mucus levels, but no effect on gastric acid and body weight.

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Background. Pomegranate is a rich source of many polyphenolic compounds including ellagitannins (punicalagin, punicalin and others). Aim. The effects of punicalagin and punicalin on adipogenesis were investigated in this study. Materials and Methods. To examine the effect of punicalagin and punicalin on adipocyte differentiation, various concentrations of punicalagin and punicalin (2- 10 μM) were applied to differentiated 3T3-L1 cells. Glyceraldehyde-3-phosphate dehydrogenase (GPDH) activity, Oil red O staining, intracellular triglyceride levels, and gene expressions of transcription factors (Peroxisome proliferator-activated receptor-γ (PPARγ), CCAATenhancer- binding proteins-α (C/EBPα), Sterol regulatory element-binding protein 1c (SREBP-1c)) and lipolysisassociated genes (hormone-sensitive lipase (HSL), Perilipin A, tumor necrosis factor-α (TNF-α)) were examined in order to investigate the effects of punicalagin and punicalin on adipocyte differentiation. Results. Punicalagin and punicalin applications caused a continuous decrease in cell size and intracellular triglyceride accumulation. GPDH activity and transcription gene expressions decreased significantly in groups that were applicated punicalagin and punicalin at high concentrations. Punicalagin, but not punicalin, down-regulated the expression of HSL and perilipin A and up-regulated the expression of TNF-α in a dose-dependent manner. In conclusion, both punicalagin and punicalin were able to inhibit the adipocyte differentiation.

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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.

Introduction: The impaired transport of leptin into the brain through a decreased permeability of the blood-brain barrier (BBB) for leptin in obesity represents one of the important mechanisms involved in leptin resistance which is characteristic in human obesity. Some pituitary tumors can increase the blood-cerebrospinal fluid barrier (BCB) permeability for peptides. BCB is a part of BBB.\r\nObjectives: The aim of our study was to search if the by-pass of BCB for pituitary hormones produced by adenomas does influence the transport of leptin into the central nervous system in obese patients.\r\nMaterials and methods: We investigated 20 males with pituitary adenomas: group A (11 patients) had cerebrospinal fluid (CSF) to serum ratio more than one for prolactin (PRL) and in some patients for growth hormone (GH) and follicle stimulating hormone (FSH), suggesting an increased permeability of BCB and a control group C (9 patients), which had CSF/serum ratio less than one for GH, PRL or FSH, suggesting an intact BCB. Both A and C groups contain subgroups of patients with obesity (body mass index, BMI>30 kg/m2) and normal body weight (BMI<25 kg/m2). In these patients we measured the CSF to serum leptin ratio in order to clinically evaluate the leptin transport into the brain. Rapid fluoroimmunoassay method with europium was used. Leptin was assayed by ELISA method.\r\nResults: The patients of group A with pituitary adenomas show a higher level of pituitary peptides, PRL and in some cases GH, FSH in CSF as compared to serum (ratio CSF/serum over 1), both in obese and non-obese. By contrast, in the same patients, there is\r\na low level of CSF leptin as compared to serum leptin (ratio CSF/serum less than 1). In the subgroup of obese patients from group A we found even less ratio of CSF to serum leptin, than in non-obese. There is a well known higher leptin concentration in the plasma of obese patients with pituitary adenomas as compared to non-obese ones (26.4?3.8ng/ml vs 12.4?3.4ng/ml, p<0.05). In the control group C, both pituitary peptides (PRL, or GH, FSH) and leptin showed a ratio CSF/serum less than 1, in all patients.\r\nConclusions: These data show a decrease in hemato-encephalic barrier permeability for leptin in obese patients through a specific mechanism, not influenced by other peptides passing through injuries of BBB produced by pituitary adenomas. It is tempting to suggest that there is a specific by-pass of BCB for pituitary peptides, in some pituitary adenomas.

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&#8217; 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.

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.