Extended Prophylactic Effect of N-tert-Butyl-α-phenylnitron against Oxidative/Nitrosative Damage Caused by the DNA-Hypomethylating Drug 5-Azacytidine in the Rat Placenta.

Antioxidant N-tert-Butyl-α-phenylnitron (PBN) partly protected embryos from the negative effects of a DNA demethylating drug 5-azacytidine during pregnancy. Our aim was to investigate PBN's impact on the placenta. Fischer rat dams were treated on gestation days (GD) 12 and 13 by PBN (40 mg/kg), followed by 5azaC (5 mg/kg) after one hour. Global methylation was assessed by pyrosequencing. Numerical density was calculated from immunohistochemical expression in single cells for proliferating (PCNA), oxidative (oxoguanosine) and nitrosative (nitrotyrosine) activity. Results were compared with the PBN-treated and control rats. PBN-pretreatment significantly increased placental weight at GD15 and GD20, diminished by 5azaC, and diminished apoptosis in GD 20 placentas caused by 5azaC. Oxoguanosine expression in placentas of 5azaC-treated dams was especially high in the placental labyrinth on GD 15, while PBN-pretreatment lowered its expression on GD 15 and GD 20 in both the labyrinth and basal layer. 5azaC enhanced nitrotyrosine level in the labyrinth of both gestational stages, while PBN-pretreatment lowered it. We conclude that PBN exerted its prophylactic activity against DNA hypomethylating agent 5azaC in the placenta through free radical scavenging, especially in the labyrinthine part of the placenta until the last day of pregnancy.

Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin's Lymphoma.

PURPOSE: This cohort study aimed to determine patterns of glycemic fluctuation and changes in metabolic parameters during and after corticosteroid administration in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy. PATIENTS AND METHODS: The study was performed in 20 patients of whom 11 had diabetes and 9 were nondiabetics. Anthropometric parameters were collected, and blood samples were taken four times during the study to analyze metabolic parameters. Capillary glucose was measured seven times a day (fasting, before mean meals, postprandial, and before bedtime) to evaluate the glycemic profile. RESULTS: In all 20 patients, acute glucocorticoid administration resulted in the elevation of average glucose levels, dominantly postprandial in the afternoon which correlates with corticosteroid peak action. In 7 out of 11 diabetics, prandial insulin was started during corticosteroid administration and discontinued afterward. Although none of our nondiabetic patients met diabetes criteria, evident is the elevation in average glycemia levels six weeks after corticosteroid administration. Potentially, even transient corticosteroid administration reduces insulin sensitivity and contributes to later glycemic disturbances. HbA1c levels were higher at the end of the study while fructosamine levels were higher during the study. CONCLUSION: Patients and health-care professionals need to be aware of corticosteroid-induced hyperglycemia. We recommend identifying risk factors, measuring glycemia before, during, and after corticosteroid administration, and starting the adequate therapy as soon as possible.

Brain tumor as a prototype of severe brain lesion in patients with "low T3 syndrome".

The purpose of our study was to contribute to better understanding of cerebrospinal fluid (CSF) as a valuable biological material in the research of brain tumors within the "low T3 syndrome", and to discuss the role of thyroid hormones in the central nervous system in subjects with severe cerebral lesions. We studied the levels of total triiodothyronine (tT3), total thyroxine (tT4), free triiodothyronine (fT3), free thyroxine (fT4), reverse triiodothyronine (rT3) and thyrotropin (TSH) in serum, and fT3, fT4, rT3 and TSH levels in CSF of patients with brain tumor, and compared the results with control group. Study results indicated a statistically significantly higher level of rT3 in serum and CSF of brain tumor patients vs. control group (p < 0.05). The rT3/fT3 ratio was highest in CSF and serum of brain tumor patients, yielding a statistically significant difference (p < 0.05). These results could suggest higher permeability of the blood-brain barrier in brain tumor patients. We also assume that rT3, in the framework of"cerebral low T3 syndrome", is also generated through local intracerebral conversion. Disruption of this process in severe cerebral lesion can lead to increased rT3 concentrations, i.e. development of the "low T3 syndrome".

Endocrinological outcomes of pure endoscopic transsphenoidal surgery: a Croatian Referral Pituitary Center experience.

AIM: To analyze early remission, complications, and pituitary function recovery after pure endoscopic endonasal transsphenoidal surgery (PEETS), a novel method in pituitary adenoma treatment. METHODS: Testing of all basal hormone values and magnetic resonance imaging (MRI) were performed preoperatively and postoperatively (postoperative MRI only in nonfunctioning adenomas) in 117 consecutive patients who underwent PEETS in the period between 2007 and 2010. The series consisted of 21 somatotroph adenomas, 61 prolactinomas, and 4 corticotroph and 31 nonfunctioning adenomas. Sixty-three were macroadenomas and 54 were microadenomas. Remission was defined as hormonal excess normalization on the seventh postoperative day in functioning adenomas and as normal MRI findings approximately four months postoperatively in nonfunctioning adenomas. The presence of hypogonadism, growth hormone deficiency, and hypothyroidism was assessed on the seventh postoperative day. Hypocortisolism was assessed through necessity for replacement therapy within 18 months postoperatively. RESULTS: Remission was achieved in 84% of patients: in 100% of microadenoma and 70% of macroadenoma patients (P<0.001, odds ratio [OR], 28.16, 95% confidence interval [CI], 1.61-491.36), respectively. Endocrinological complications occurred in 17.1% of patients: in 9% of microadenoma and 24% of macroadenoma patients (P=0.049, OR, 3.06; 95% CI, 1.03-9.08). Duration of empirical hydrocortisone replacement therapy was significantly shorter in microadenoma patients (P<0.001). Thirty-five percent of preoperatively present hormonal deficiencies improved after the surgery. Between tumor types there were no significant differences in remission, complications, and normal pituitary function recovery. CONCLUSION: Patients with microadenomas had higher remission and lower complication rates following PEETS, emphasizing the necessity for early detection and treatment of pituitary adenomas. PEETS is a discussion-worthy method for microprolactinoma treatment.

Intrathyroid parathyroid carcinoma with intrathyroidal metastasis to the contralateral lobe: source of diagnostic and treatment pitfalls.

Intrathyroidal parathyroid carcinoma is extremely rare clinical entity with potentially multiple diagnostic pitfalls. We report a case of 40-year-old man presented with classical manifestations of primary hyperparathyroidism, severe hypercalcemia and profoundly increased serum parathyroid hormone level. Neck ultrasonography demonstrated multinodular goiter with predominant 34 mm nodule in left thyroid lobe. Additional 16 mm nodule was found beneath the left lobe. Routine percutaneous fine-needle aspiration of predominant nodule indicated follicular thyroid carcinoma, while left inferior nodule was confirmed to be of parathyroid origin. The patient underwent surgery, during which frozen sections identified medullary thyroid carcinoma with metastasis to upper mediastinal lymph node. Permanent sections of the predominant left lobe nodule revealed intrathyroidal parathyroid carcinoma surrounded with multiple microscopic metastases. Left inferior nodule was metastatic lymph node. Additional 10 mm intrathyroidal metastasis of primary parathyroid carcinoma was found within right thyroid lobe. This case indicates that fine-needle-aspiration and intraoperative biopsy are of limited value in diagnosing parathyroid carcinoma, especially if localized intrathyroidally. Oncological en-block resection is treatment of choice, implying ipsilateral lobectomy in case of thyroid invasion. This firstly described case of intrathyroidal parathyroid carcinoma causing intrathyroidal dissemination may influence future treatment strategies.

Incidence of pituitary tumors in the human population of Croatia.

Pituitary tumors are rare tumors (less then 10%) of the central nervous system (CNS), which malignicity depends on their localization, meanwhile, their biological nature is benign. The diameter they have is mostly less then 10 mm (microadenomas), but sometimes could be 10 mm (macroadenomas) to 5 cm and more and then are usually nonfunctional (about 20% of all pituitary tumors). Clinical presence depends on their localisation and hormonal activity. In the Center for Clinical Neuroendocrinology and Pituitary Diseases, in the last working 10 years, there were treated and examined 504 patients from Croatia, all with pituitary tumors: 182 patients with prolactinomas, 137 with acromegaly, 70 with Morbus Cushing (Mb. Cushing), and 115 patients with nonfunctional pituitary tumors. The patient's classification is based on regional (Mediterranean and continental region, 20 counties) and the state level. In our analysis we haven't found difference in incidence of tumors between Mediterranean and continental region.