Study of endocrine disruptor effects in AVP and OT mediated behavioral and reproductive processes in female rat models.

Environmental exposures may have endocrine disruptor (ED) effects, e.g., a role for halogenated hydrocarbon chlorobenzenes in increasing vasopressin (AVP), oxytocin (OT) secretion and, in association, anxiety and aggression in male rats has been shown. Our aim is to investigate whether 1,2,4-trichlorobenzenehexachlorobenzene= 1:1 (mClB) treatment of female rats also shows ED effects and reproductive biology differences, and whether AVP may have a mediator role in this? Female Wistar rats were treated (0.1; 1.0; 10.0 µg/bwkg/day) with mClB (by gastrictube) and then 30; 60; 90 days after treatment anxiety (open field test) and aggressive (resident intruder test) behaviors AVP, OT concentrations from blood plasma samples were detected by radioimmunoassay on 30; 60; 90 days. Treated female rats were mated with untreated males. Mating success, number of newborn and maternal aggression on the neonates were monitored. Results showed that AVP, OT levels; and anxiety, aggressive behaviors; and mothers' aggression towards their offspring increased significantly in relation to the duration and the dose of mClB treatment. But mating propensity and number of offspring decreased. Patterns of AVP, OT release and anxiety, aggression behaviors, and reproductive-related behaviors were correlated. Consistent with the literature, our studies confirmed the role of AVP and OT in different behavioral effects.

Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care.

Introduction: The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care. Patients and Methods: Twenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. Results: T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01). Conclusion: In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Study of the Potential Endocrine-Disrupting Effects of Phenylurea Compounds on Neurohypophysis Cells In Vitro.

Homeostatic disruptor agents, and endocrine disruptor compounds (EDC) specifically, can originate from agricultural and industrial chemicals. If they modify the adaptation of living organisms as direct (e.g., by altering hormone regulation, membrane functions) and/or indirect (e.g., cell transformation mechanisms) factors, they are classified as EDC. We aimed to examine the potential endocrine-disrupting effects of phenylurea herbicides (phenuron, monuron, and diuron) on the oxytocin (OT) and arginine-vasopressin (AVP) release of neurohypophysis cell cultures (NH). In our experiments, monoamine-activated receptor functions of neurohypophyseal cells were used as a model. In vitro NH were prepared by enzymatic (trypsin, collagenase) and mechanical dissociation. In the experimental protocol, the basal levels of OT and AVP were determined as controls. Later, monoamine (epinephrine, norepinephrine, serotonin, histamine, and dopamine) activation (10-6 M, 30 min) and the effects of phenylurea (10-6 M, 60 min) alone and in combination (monoamines 10-6 M, 30 min + phenylureas 10-6 M, 60 min) with monoamine were studied. OT and AVP hormone contents in the supernatant media were measured by radioimmunoassay. The monoamine-activated receptor functions of neurohypophyseal cells were modified by the applied doses of phenuron, monuron, and diuron. It is concluded that the applied phenylurea herbicides are endocrine disruptor agents, at least in vitro for neurohypophysis function.

The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL.

Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs), which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU) and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH), which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH) and cells of prolactinomas (PRLOMA). PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL) release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1) uron agents separately did not change ACTH and PRL release in AdH culture; (2) ACTH secretion in arginine vasopressin- (AVP-) activated AdH cells was significantly increased by EDC treatment; (3) ED agents increased the basal hormone release (ACTH, PRL) in PRLOMA cells; and (4) EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.

Effects of extremely low frequency electromagnetic fields on turkeys.

Several studies have examined the potential biological effects of electromagnetic fields (EMF) on birds; however, little attention has been paid to the extremely low frequency (ELF; 0-300 Hz; 0-50 µT) radiation found in an urbanized environment. For monitoring the effects of ELF EMF, we used a turkey (Meleagris gallopavo) model, because the nucleated erythrocytes of turkeys contain ß-adrenoceptors, and norepinephrine- (NE-) activated ß-adrenoceptors have an important role in physiological and behavioral processes. Our aims were the following: 1) to investigate the intracellular mechanisms; 2) to compare the intracellular mechanisms in the treated and control groups over time, considering inter-individual differences and intra-subject correlations; 3) and to study the reversible nature of the response. The turkeys in the treatment group were treated in vivo with ELF EMF (50 Hz; 10 µT) for 3 wk after a 1-wk-long adaptation period. The animals were not exposed to ELF EMF during the regeneration period (5 wk following the exposure). The NE-activated ß-adrenoceptor function was detected by measuring the amount of 3΄5΄-cyclic-adenosine-monophosphate (cAMP), and the biochemical enzyme parameters were defined. Repeated measurements of cAMP levels were analyzed using marginal models and a piecewise linear mixed model to compare treatment and control groups over time. According to our results, NE-activated ß-adrenoceptor function was decreased in the treated birds in a time-dependent manner, while there were no differences between toxicological parameters in the serum, compared to the normal ranges. The decreased NE-dependent ß-adrenoceptor function could be compensated by the homeostatic complex during the 5-wk regeneration period. Extended experimental periods and more sophisticated analysis methods may help prevent harmful environmental effects on birds; furthermore, these findings could affect public health and the economy.

The impact of post-radioiodine therapy SPECT/CT on early risk stratification in differentiated thyroid cancer; a bi-institutional study.

OBJECTIVE: SPECT/CT has numerous advantages over planar and traditional SPECT images. The aim of this study was to evaluate the role of post-radioiodine therapy SPECT/CT of patients with differentiated thyroid cancer (DTC) in early risk classification and in prediction of late prognosis. PATIENTS AND METHODS: 323 consecutive patients were investigated after their first radioiodine treatment (1100-3700 MBq). Both whole body scan and SPECT/CT images of the head, neck, chest and abdomen regions were taken 4-6 days after radioiodine therapy. Patients were re-evaluated 9-12 months later as well as at the end of follow up (median 37 months). RESULTS: Post-radioiodine therapy SPECT/CT showed metastases in 22% of patients. Lymph node, lung and bone metastases were detected in 61, 13 and 5 patients, respectively, resulting in early reclassification of 115 cases (36%). No evidence of disease was found in 251 cases at 9-12 months after radioiodine treatment and 269 patients at the end of follow-up. To predict residual disease at the end of follow-up, the sensitivities, specificities and diagnostic accuracies of the current risk classification systems and SPECT/CT were: ATA: 77%, 47% and 53%; ETA: 70%, 62% and 64%; SPECT/CT: 61%, 88% and 83%, respectively. There was no difference between cohorts of the two institutions when data were analyzed separately. CONCLUSIONS: Based on our bi-institutional experience, the accuracy of post-radioiodine SPECT/CT outweighs that of the currently used ATA and ETA risk classification systems in the prediction of long-term outcome of DTC.

Effects of chronic and subtoxic chlorobenzenes on adrenocorticotrophic hormone release.

Many environmental chemicals and pesticides have been found to alter neuroendocrine communication in exposed biological objects. The environmental loads have primary and secondary effects that can alter the homeostatic regulation potential. Since it is difficult to avoid human exposition, a potentially important area of research to develop in vivo and in vitro experimental models. In this context, the primary aim of this study was to demonstrate the effects of chlorobenzenes on adrenocorticotrophic hormone (ACTH) release. In our experimental study, male Wistar rats were exposed to 0.1, 1.0 and 10 µg/b.w. (body weight)kg of 1,2,4- trichlorobenzene and hexachlorobenzene (ClB) mix via gastric tube for 30, 60 or 90 days. At the endpoints of the experiment blood samples were taken and animals were decapitated. Primary, monolayer adenohypophysis cell cultures were prepared by enzymatic and mechanical digestion. The ACTH hormone content in serum and supernatant media was measured by immuno-chemiluminescence assay. The Mg(2+)-dependent ATPase activity was determined by modified method of Martin and Dotty. Significant differences were detected in the hormone release between the control and treated groups. The hormone release was enhanced characteristically in exposed groups depending upon the dose and duration of exposure. The Mg(2+)-ATPase activity enhanced after chronic and subtoxic ClB exposition. Light microscopy revealed that the adenohypophysis seemed to be more abundant. Results indicate that Wistar rats exposed to subtoxic ClB have direct and indirect effects on hypothalamus-hypophysis-adrenal axis.

[Endoscopic ultrasound-guided ethanol ablation: an alternative option for the treatment of pancreatic insulinoma]. / Endoszkópos ultrahangvezérelt alkoholos ablatio: alternatív terápia a pancreasinsulinomák kezelésében.

Endoscopic ultrasound is the most accurate imaging modality for the diagnosis of pancreatic cancer, and endoscopic ultrasound-guided fine needle injection has already been used for palliative interventions. Surgical resection is currently the standard treatment for pancreatic insulinoma. Medical treatment may be necessary for symptomatic patients with unresectable disease. Case reports have been published about the success of endoscopic ultrasound-guided alcoholic ablation, but it has not been reported previously in Hungarian literature. The authors present the history of an 83-year-old woman who was evaluated because of repeated hypoglycemic coma occurring during the night. Endosonographic image and laboratory findings (elevated serum insulin and chromogranin A) revealed pancreatic insulinoma. Because of severe comorbidities and high risk of surgical resection, the decision was made to ablate the insulinoma by endoscopic ultrasound-guided alcohol injection. A total of 3 mL 95% ethanol was injected into the tumor. Despite the discontinuation of the diazoxide therapy the hypoglycemic episodes disappeared. This case history confirms that endoscopic ultrasound-guided alcoholic ablation is a novel, minimal invasive alternative treatment for patients with pancreatic neuroendocrine tumors in whom surgery is not feasible.

[Various neuroendocrine tumors in a family with multiple endocrine neoplasia type 1]. / Neuroendokrin daganatok multiplex endokrin neoplasia 1-es típusában szenvedo családban.

When multiple endocrine tumors are detected more tests are required to diagnose endocrine tumor syndromes. The authors report the case history of a patient with clinical manifestation of multiplex endocrine neoplasia type 1 (parathyroid adenoma, pancreatic neuroendocrine tumor, pituitary tumor, adrenal gland tumors and thymic neuroendocrine carcinoma). Genetic screening proved a novel stop codon mutation of the MEN1 gene in the patient and in two other members of the family. The son of the index patient showed clinical symptoms of pancreatic neuroendocrine tumor (insulinoma) and parathyroid adenoma. One of the two daughters was also positive for the same mutation, however, she had no clinical symptoms. The authors review current knowledge on the genetic background of multiple endocrine syndrome type 1, the role of menin and the usefulness of gene mutation screening.

[In the labyrinth of calcium metabolism]. / A kalcium-anyagcsere útvesztoi.

The authors present the case of a 27-year-old male patient. In 2010, he suffered from a bone fracture of the pelvis. As imaging techniques showed multiple osseal lytic lesions, diagnostic investigations were performed for multiple myeloma. Later, a mass lesion measuring 37 mm in size was removed from the left side of his mandible. Histology revealed a giant-cell tumour of the bone and oncologic therapy was considered. However, before this planned treatment a PET-CT was performed, which showed numerous distinct lesions with enhanced glucose metabolism in the skeleton as well as in soft tissue behind the right lobe of the thyroid. Hence, the patient was referred to endocrinologists. On the basis of severe hypercalcemia (serum calcium 3.66 mmol/l) and high serum parathyroid hormone level (162.5 pmol/l) the diagnosis of a right sided parathyroid tumour was established. After surgical excision of the parathyroid tumour, high levels of serum calcium and parathyroid hormone returned to normal. Histology failed to show malignancy and the patient recovered soon. This case report may shed some light on the importance of serum calcium measurements and the differential diagnostic significance of primary hyperparathyroidism.