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Bot III neurotoxin is the most lethal α neurotoxin purified from Buthus occitanus tunetanus scorpion venom. This toxin binds to the voltage-gated sodium channel of excitable cells and blocks its inactivation, inducing an increased release of neurotransmitters (acetylcholine and catecholamines). This study aims to elucidate the involvement of cholinergic and adrenergic receptors in pathogenesis and inflammatory response triggered by this toxin. Injection of Bot III to animals induces an increase of peroxidase activities, an imbalance of oxidative status, tissue damages in lung parenchyma, and myocardium correlated with metabolic disorders. The pretreatment with nicotine (nicotinic receptor agonist) or atropine (muscarinic receptor antagonist) protected the animals from almost all disorders caused by Bot III toxin, especially the immunological alterations. Bisoprolol administration (selective β1 adrenergic receptor antagonist) was also efficient in the protection of animals, mainly on tissue damage. Propranolol (non-selective adrenergic receptor antagonist) showed less effect. These results suggest that both cholinergic and adrenergic receptors are activated in the cardiopulmonary manifestations induced by Bot III. Indeed, the muscarinic receptor appears to be more involved than the nicotinic one, and the β1 adrenergic receptor seems to dominate the β2 receptor. These results showed also that the activation of nicotinic receptor leads to a significant protection of animals against Bot III toxin effect. These findings supply a supplementary data leading to better understanding of the mechanism triggered by scorpionic neurotoxins and suggest the use of drugs targeting these receptors, especially the nicotinic one in order to counteract the inflammatory response observed in scorpion envenomation.

Objectives: Optimal thyroid function is necessary for an effective fertility. Many authors have suggested that thyroid function has an impact on IVF outcome. Conversely, IVF has been suggested to induce changes in thyroid function. The aim of this study was to determine the nature and the timing of alterations in thyroid function, throughout controlled ovarian hyperstimulation, from the beginning of therapy to the day of triggering ovulation. And make a clarification of the current recommendations of the thyroid function during hormonal stimulation., Methods: Subjects were recruited from March 2013 to July 2013 at the Hospital of the University of Reims. The studied population consisted of 50 infertile patients who had undergone IVF/ICSI cycles. Thyroid axis exploration was realized before therapy and at every hormonal dosage during ovarian monitorage., Results: Prematuary fluctuations were observed without impact on pregnancy rate. We could detect potential hypothyroid women thanks to this dosage and define a connection between pregnancy rate and TSH with a threshold closer to 1mUI/L than 2,5mUI/L defined by the endocrine society., Conclusions: The link between thyroid function, forecast of conception and pregnancy is well documented. Currently, there is no recommendation on the rate of TSH targets for the patients in medical assisted procreation., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Context: Ectopic GHRH secretion is a rare cause of acromegaly, and case reports are mainly isolated., Setting: From the registry of the sole laboratory performing plasma GHRH assays in France, we identified cases of ectopic GHRH secretion presenting with acromegaly between 1983 and 2008., Patients: Twenty-one patients aged 14-77 yr were identified from 12 French hospitals. Median GHRH was 548 (270-9779) ng/liter., Main Outcome Measures: Outcome measures included description of tumor features and outcome and the relation between plasma GHRH values and tumor site, size, and spread., Results: The primary neuroendocrine tumor was identified for 20 of 21 patients (12 pancreatic, seven bronchial, one appendicular). Tumors were large (10-80 mm), identified on computed tomography scan in 18 cases and by endoscopic ultrasound and somatostatin receptor scintigraphy in two. Somatostatin receptor scintigraphy had a similar sensitivity to computed tomography scan (81 vs. 86%). Tumors were all well differentiated; 47.6% had metastasized at the time of diagnosis of acromegaly. After a median follow-up of 5 yr, 85% of patients were alive. Ninety-one percent of patients whose tumor was completely removed were considered in remission, and most had normalized plasma GHRH. The remaining patients were treated with somatostatin analogs: IGF-I normalized except for one patient who required pegvisomant, but GHRH levels remained elevated. No correlations were found between GHRH levels and tumor site or size or the existence of metastases. Identification of increased plasma GHRH during follow-up was an accurate indicator of recurrence., Conclusions: The prognosis of endocrine tumors responsible for GHRH secretion appears relatively good. Plasma GHRH assay is an accurate tool for diagnosis and follow-up.

With an incidence of 5% in the female population, genital malformations are a frequent clinical occurrence presented by Oppelt et al. (2007) [1]. First, we have to diagnostic them and search for extra genital malformation when it is necessary. Think about maturity-onset-diabetes-of-the young 5 (MODY-5) when there's a personnel or family story of diabetes. This is often within the competence of the diabetologist and our speciality can be put in contribution in the research for the associated genital malformation. We report on the case of a young woman age of 19 with diabetes diagnosed during her adolescence, a nephropathy with polycystic kidneys, biological cytolysis, a bicornuate unicervical uterus while this may be a clinical diabetes MODY-5 confirmed by the discovery of the complete deletion of the gene coding for HNF-1 beta in the heterozygous state., ((c) 2010 Elsevier Masson SAS. All rights reserved.)

Male infertility is present in 50% of couple infertility. Diagnosis of infertility requires methodical and rigorous approach based upon knowledge of the pathophysiology and the causes of infertility.

Although the objective of the urologist is to correct the factors of male infertility and to favour natural procreation, the strategy must consider also the couple and the female aspects of infertility. Some types of male infertility require specific treatment. In severe cases, recent advances in medical assistance to procreation have changed the prognosis of male infertility. Pregnancy can be obtained by the means of gamet manipulation and spermatozoid selection. Nevertheless, such techniques expose to genetic disorders transmission. Subsequently, genetic assessment is required during male infertility management, especially for difficult cases.

The diagnosis of male infertility requires methodical approach which is primarily clinical, aimed at identifying all potential factors. Biological and radiological assessments allow diagnosis confirmation, and evaluation of both prognosis and therapeutic strategy.

Purpose: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR)., Methods and Materials: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin., Results: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, except for pituitary deficiency, were reported, with a probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8 years, respectively. Nonfunctioning status was the sole unfavorable factor (p = 0.0016)., Conclusions: Surgery plus FSR is safe and effective. FSR focused to the target volume seems more suitable than standard radiotherapy, and standard fractionation reduces the risk of optic neuropathy sometimes observed after single-dose radiosurgery. Therefore, FSR allows us to consider combined transrhinoseptal surgery and early radiotherapy, with a curative goal without patient selection.

Background and Purpose: To optimize and reduce the toxicity of pituitary adenoma irradiation, we evaluated the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR) in 51 patients with functional adenoma; 12 of them had Cushing's disease., Patients and Methods: Eleven females and one male, median age: 49 years, 8 of them relapsed and 4 had persistent hormonal secretion after surgery. The delivered dose was 50 grays (Gy) (5 x 1.8 Gy/week) using 5 convergent micro-beams scanning in arc therapy mode. The median planned target volume (PTV) receiving 90 to 100% of the total dose was 2,1 cm(3). We used relocatable non-invasive stereotactic device Brain Lab, and adapted Linac for stereotactic radiotherapy., Results: Nine out of twelve patients (75%) presented with complete remission after a median time of 29 months, 3/12 patients with partial remission. Actuarial probability to have hormonal persistent secretion was 88% at on year, 44% from 3 to 5 years, 22% at 7 years, and 11% to 0% after 7 years. The 12-corticotroph adenomas were significantly (p=0.007) more radiosensitive than 39 non-corticotroph adenomas. Toxicity was significantly lower for corticotrope adenoma, with no radio-induced pituitary deficiency and no neurological or optic injury., Conclusions: Combined surgery and FSR appears to be safe and effective for treatment of pituitary adenomas. However, long-term follow-up is required to determine the impact in terms of tumor response and hormone deficiency. The focused treated volume obtained by FSR seems more suitable for these benign tumours than standard radiotherapy. In addition to this conformal approach, the use of standard fractionation reduced the risk of severe damage to the optic chiasma, which is sometimes observed after radiosurgery and is inherent in single fraction radiotherapy.

Adrenocortical carcinoma (ACC) is a rare tumour with a poor prognosis. Cisplatin is the most widely tested cytotoxic agent in this disease. A total of 18 patients with advanced ACC were enrolled. Cytotoxic therapy consisted of etoposide (VP16) (100 mg m(-2) day(-1) on days 1-3) and cisplatin (100 mg m(-2) day(-1) on day 1) every 4 weeks. Mitotane treatment was maintained during chemotherapy in 14 patients. A complete response was observed in three cases and a partial response in three cases, giving an overall response rate of 33%. Tumour response was observed in three of the six patients with progressive disease during treatment with mitotane given at an effective dosage, as shown by serum levels >14 mg l(-1). Toxic effects were as expected and were non-life-threatening; no treatment interruption was required.

Purpose: In order to optimize cerebral benign tumor irradiation, fractionated stereotactic radiotherapy allows a focused-volume irradiation (2.1 cm3, 16 mm diameter) under standard fractionation conditions. Results of a retrospective and multicentric analysis are presented., Patients and Methods: Fractionated stereotactic radiotherapy uses the ballistic principles of the radiosurgery: stereotactic localization, multi-beam irradiation, secondary collimation, three-dimensional dosimetry. Standard fractionation is possible with a re-locatable non-invasive stereotactic device. The technique has been used for treating pituitary adenomas (86 patients), acoustic neuromas (32 patients) and cavernous meningiomas (26 patients)., Results: 1) pituitary adenomas: cumulative tumoral objective-response rates (42 patients) were respectively 42%, 69% and 88% at 24, 48 and 60 months. The cumulative endocrinologic objective-response rates (32 patients) were respectively 53%, 75% and 85% at 24, 48 and 60 months. The cumulative risk of radio-induced hormonal deficiency varied from 18% (growth hormone [GH]) to 42% for TSH (thyroid stimulating hormone) at 48 months. No other complication was observed; 2) acoustic neuromas: 33 tumors, < 25 mm in diameter, were treated in 32 patients. Tumor control was observed in 29/33 tumors: 14 were stable, 15 decreased and three progressed. Useful hearing was maintained in 9/10 patients. Only three patients (9%) presented persistent complications; 3) cavernous meningioma: 17/19 clinical responses were noted, 20 tumoral stabilisations, one partial response and one progression (22 magnetic resonance imaging [MRI] evaluable patients). One unilateral radio-induced blindness was observed., Conclusion: For these benign tumors, the focused target volume obtained by the fractionated stereotactic radiotherapy seems to be better adapted to the treatment of limited benign tumors than standard radiotherapy. The use of standard fractionation reduces the risk of severe normal tissue damage, sometimes observed for radiosurgery and inherent in the use of single fraction.