ACTA ENDOCRINOLOGICA (BUC)

Context. Adipokines secreted by fat cells are vital to the control of energy metabolism, communicating the nutrient status with the tissues responsible for controlling both energy intake and expenditure and insulin sensitivity. Objective. We aimed to prove in an experimental animal study that maternal obesity has long term adverse fetal metabolic consequences, which pass on even to the next generation of descendants. Design. The effects of maternal obesity have been studied on animal model using 50 obese female Wistar rats, in which we induced obesity by high-calorie high-fat diet administered by gavage. Subjects and Methods. Obese rat females were sacrificed at gestation term and we analyzed the secretion of adipokines from maternal venous blood: leptin and adiponectin, placental, pancreatic, liver and brain homogenates lipid peroxidation levels estimated by: MDA (malonyl-dialdehyde), total thiols and GSH – as antioxidant factors and routine biochemistry. Results. Low levels of adiponectin and increased levels of leptin positively correlated with the value of placental and fetal tissue lipid peroxidation (from the liver, pancreas and brain) measured by elevated MDA and total thiols and low levels of GSH. The lipid peroxidation in the organs examined generated consistent results, showing high levels of peroxidation expressed through high values of MDA in the groups with Omega 6 supplements respectively no supplementation, and low levels of antioxidants expressed through glutathione and thiols. Conclusions. Endocrine secretion of adipokines from the adipocytes and the recruited macrophages of obese mothers is positively correlated with placental and tissue lipid peroxidation level and routine biochemical parameters.

Background. Arecoline, a plant alkaloid of betel nut, is consumed by millions of people, for increased capacity of work. It causes immunosuppression, hepatotoxicity, and disturbance in antioxidant production, but it stimulates HPA axis and induces thyroid dysfunction.\r\nAim. To investigate the role of arecoline on adrenal activity, glycemia and glycogen profile in mice.\r\nMaterials and methods. Arecoline was injected intraperitoneally at a dose of 10 mg/kg body wt for 20-60 min for acute administration. In chronic administration the same dose was used daily for 15 days. Corticosterone, epinephrine, norepinephrine, blood glucose and liver glycogen profiles were measured after 20, 40 and 60 min, in acute administration and after 15 days in chronic administration.\r\nResults. Arecoline in acute administration increased corticosterone, norepinephrine and epinephrine levels and induced hyperglycemia with depletions of liver glycogen. But\r\nchronic arecoline administration with the same dose for 15 days caused ultrastructural degenerations of adrenal cortex and medulla with the elevation of corticosterone, and\r\ndepletions of norepinephrine and epinephrine levels. Arecoline also caused hypoglycemia and elevated liver glycogen. Atropine (arecoline receptor antagonist) prevented arecoline action on adrenal activity or blood glucose ? liver glycogen interaction.\r\nConclusion. The findings indicate that arecoline initially stimulates adrenal activity, but subsequently inhibits it with alterations of glycemic and glycogen profiles. Arecoline action is mediated by arecoline receptor in mice. Arecoline may have immunological action via adrenal hormonal suppression in mice.

Context. The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. Objective. The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. Design. The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3β-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. Methods. Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. Results. All the inhibitors attenuated the hCGinduced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. Conclusion. hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.

Introduction. The determination of phenylalanine (Phe) and tyrosine (Tyr) levels in blood plasma is very important not only in early diagnostic, but also in monitoring the treatment of phenylketonuria (PKU). Purpose. We present a simple, sensitive and accurate procedure to determine simultaneously the plasma concentrations of Phe and Tyr. Procedure. The measurement involves two steps: a) separation of plasma (from blood prelevated on heparin), isolation and preparation of a concentrated solution of amino acids (by ion-exchange column chromatography on Dowex- 50X8), and b) determination of Phe and Tyr concentrations in the solution of amino acids by HPLC (using a Dionex Ultimate 3000 instrument equipped with a diode array detector). The analytical column was a Thermo Scientific Acclaim 120, C18, 5 μm Analitic (4.6 x 250 mm), coupled with an Acclaim C18 guard column. The values of Phe and Tyr concentrations in plasma of several patients were calculated using a calibration curve made with standards of Phe (1834.4 μmol/L in deionized water) and Tyr (600 μmol/L in deionized water). Concentrations as low as 24 μmol/dL of Phe and 15 μmol/dL of Tyr could be determined. Conclusion. The whole procedure presented here is relatively simple, rather inexpensive, however very sensitive and accurate. Consequently, it is very adequate for confirming the diagnosis of PKU in patients with neonatal hyperphenylalaninemia, as well as for monitoring the plasma concentrations of Phe and Tyr in patients with PKU.

Objective. Opium is a narcotic drug that is commonly abused. The prescription of pharmaceutical derivatives of opium is limited due to their possible harmful effects on the body’s metabolism and tolerability by patients. The aim of the present study was to evaluate the effects of chronic opium consumption on some sexual and thyroid hormones in diabetic and non-diabetic male and female rats. Material and Methods. This experimental study was conducted on 56 Wistar rats. The animals were divided into diabetic addicted (DA), diabetic non-addicted (DNA), non-diabetic addicted (NDA) and non-diabetic non-addicted (NDNA) groups of male and female rats. Peripheral blood samples were collected to measure the thyroid and sex hormone levels. Student’s t-test was used to compare the mean values of the hormones between two groups. Results. T3 serum level in male addicted groups significantly increased in comparison with non-addicted ones in both diabetic and non-diabetic groups. The testosterone level of male rats decreased due to the consumption of opium while it was significantly increased in diabetic and NDNA female rats in comparison with non-addicts. In DNA female animals, the mean level of 17-hydroxyprogesterone increased significantly compared with non-diabetic groups, however, it decreased in addicted females (diabetic and non-diabetic) in comparison with non-addicts. The level of DHEA-S increased significantly in diabetic and NDA male rats as compared with the non-addicted group. Conclusion. Opium affects the endocrine system in a sex-dependent manner, and opium could have different effects in diabetic and non-diabetic conditions.

A 54 years old man, who had undergone a cystectomy and urinary diversion surgery 31 years previously, complained of progressive generalized bone pain, muscle weakness and walking abnormality for six months. Laboratory investigations revealed elevated alkaline phosphatase, high serum chloride level and metabolic acidosis. Osteomalacia was suspected due to clinical and laboratory findings. Osteomalacia due to hyperchloremic metabolic acidosis is a complication of urinary diversion. Regular monitoring of pH, chloride, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.

Resistant Graves’ disease in pregnancy is a rare entity. The clinical situation poses immense difficulty to the treating endocrinologist and obstetrician in optimizing maternal and fetal heath. No guidelines till date are available to manage resistant Grave’s disease in pregnancy. We hereby present a case series on resistant Grave’s in pregnancy and our institute experience in managing this rare and challenging clinical entity. Definitive management is total thyroidectomy in second trimester. Higher doses of ATDs and betablockers may have its fetopathic effects. Use of immunosuppressive agents are not advised in pregnancy to suppress the TRAb titre. Steroid therapy may be used as an adjuvant to permissible doses of anti-thyroid medications to curb the thyrotoxicosis in pregnancy. An alternate fetal friendly ATD is not available to add on to existing ATDs. TRAb estimation in maternal blood is mandatory. Mothers need frequent monitoring of cardiac status and need to avoid factors that can cause cardiac decompensation. Fetal surveillance includes growth monitoring and biophysical profile at nearby intervals, helps to ascertain the effects of excess thyroid hormones, TRAb and anti-thyroid drugs. Immediate neonatal cord blood screening for thyroid abnormalities is necessary. Maternal and fetal management in such a clinical situation is multidisciplinary.

Background. The modern management of phenylketonuria (PKU) consists of generalized newborn screening (NBS) for hyperphenylalaninemia (HPA), confirmation of HPA in children detected in the NBS, introduction of dietary treatment in the first weeks of life, followed by monitoring the treatment of PKU for decades to maintain phenylalaninemia within the limits that will not affect the brain. The present study aimed to evaluate the usefulness of two chromatographic methodologies for determination of plasma Phe level in the routine management of PKU: the two dimensional thin layer chromatography (2D - TLC) and the high performance liquid chromatography (HPLC) procedures, respectively. Material and Methods. Samples of blood from 23 children with HPA detected by neonatal screening or with confirmed PKU who received treatment by low-Phe diet were analyzed to estimate the plasma Phe level by the two chromatographic procedures. Results. In case of three subjects the very low concentrations of plasma Phe could not be detected by the 2D - TLC methodology, since the spot was not visible on the chromatogram. In four patients the differences between the values of plasma Phe determined by the two methodologies are not statistically significant, while in fifteen subjects the differences are highly statistically significant. This is due to the greater errors that appear in the case of 2D - TLC methodology. In the range of concentrations of plasma Phe higher than 360 μmol/L (which is the cut-off value for HPA), although in four cases there were statistically significant differences in the level of plasma Phe determined by the two methodologies, the value obtained by the 2D - TLC methodology was high enough to influence the decision of changing the diet so that HPA is kept under control. In addition, the intense spot of Phe on the 2D - TLC chromatogram may be detected even by un unexperienced laboratory specialist. Conclusion. The HPLC procedure for measurement of plasma Phe level is very suitable to be used in the routine management of PKU. The 2D - TLC procedure may be accompanied by relatively high errors; however, it detects patients with severe PKU.

Objective. This study was undertaken to examine prognostic factors in patients with pancreatic neuroendocrine tumors (PNET) undergoing surgical treatment to evaluate the prognostic value of recently introduced immunohistochemical staining methods of CD10 and cytokeratin 19. Materials and Methods. Tumors were classified on the basis of 2004 WHO Classification Guidelines and European Neuroendocrine Tumor\r\nSociety (ENETS) grading system. Immunohistochemical staining with Ki- 67, CD10 and cytokeratin 19 was performed. Results. A total of 36 patients with a mean age of 53.7 ? 12.0 years were included. Overall, 33 patients had a long-term follow-up with 10 patients (30.3%) experiencing recurrence. Seven\r\npatients (21.1%) died. Clinical parameters that were associated with recurrence included liver metastasis at the time of surgery and extra-pancreatic invasion (p < 0.005). Positive surgical margins, extra-pancreatic invasion, and multi-focal disease were associated with reduced survival (p < 0.05). In addition, there was an association between\r\nsurvival and WHO 2004 classification (p < 0.05).\r\nConclusions. Although vascular and peripancreatic invasion showed increased risk of recurrence, they were unrelated to survival. Of the histopathological examinations, Ki-67\r\nand mitotic activity showed a correlation with both recurrence and survival, while immunohistochemical\r\nstaining with cytokeratin 19 and CD 10 did not provide adequate prognostic information.

Carbimazole is a common drug used to treat hyperthyroidism. Agranulocytosis is a known adverse effect of these anti-thyroid drugs but plasmacytosis simulating multiple myeloma is a very uncommon manifestation of this drug. We report here the case of a patient of hyperthyroidism who developed febrile neutropenia while on carbimazole with the preliminary marrow findings simulating plasma cell myeloma.