Effects of disrupted ghrelin receptor function on fear processing, anxiety and saccharin preference in mice.

BACKGROUND: Obesity is a risk factor for stress-related mental disorders such as post-traumatic stress disorder. The underlying mechanism through which obesity affects mental health remains poorly understood but dysregulation of the ghrelin system may be involved. Stress increases plasma ghrelin levels, which stimulates food intake as a potential stress-coping mechanism. However, diet-induced obesity induces ghrelin resistance which in turn may have deleterious effects on stress-coping. In our study, we explored whether disruption of ghrelin receptor function though high-fat diet or genetic ablation affects fear processing, anxiety-like behavior and saccharin preference in mice. METHODS: Adult male C57BL6/J mice were placed on a standard diet or high-fat diet for a total period of 8 weeks. We first established that high-fat diet exposure for 4 weeks elicits ghrelin resistance, evidenced by a blunted hyperphagic response following administration of a ghrelin receptor agonist. We then carried out an experiment in which we subjected mice to auditory fear conditioning after 4 weeks of diet exposure and evaluated effects on fear extinction, anxiety-like behavior and saccharin preference. To explore whether fear conditioning as such may influence the effect of diet exposure, we also subjected mice to auditory fear conditioning prior to diet onset and 4 weeks later we investigated auditory fear extinction, anxiety-like behavior and saccharin preference. In a final experiment, we further assessed lack of ghrelin receptor function by investigating auditory fear processing, anxiety-like behavior and saccharin preference in ghrelin receptor knockout mice and their wild-type littermates. RESULTS: High-fat diet exposure had no significant effect on auditory fear conditioning and its subsequent extinction or on anxiety-like behavior but significantly lowered saccharin preference. Similarly, ghrelin receptor knockout mice did not differ significantly from their wild-type littermates for auditory fear processing or anxiety-like behavior but showed significantly lower saccharin preference compared to wild-type littermates. CONCLUSION: Taken together, our data suggest that disruption of ghrelin receptor function per se does not affect fear or anxiety-like behavior but may decrease saccharin preference in mice.

[Non Hodgkin's lymphomas: a major breakthrough with immunotherapy]. / Les lymphomes non hodgkiniens: apports considérables de i'immunothérapie.

Non hodgkin's lymphomas are a group of haematological malignancies in which spectacular progress has been made over the last ten years thanks to immunotherapy. Furthermore, the new WHO classification, based upon tumour immunology, the degree of tumour differentiation and cytogenetic abnormalities, has finally improved identification of each lymphoma and has enabled comparison of homogeneous populations between different clinical studies. The increase in the incidence of non hodgkin's lymphoma is related to the aging of the population and to other factors that are yet to be elucidated--a real challenge for the future. We have tried to offer an overview of the latest therapeutic advances, with a focus on (radio-) immunotherapy and haemopoietic stem cell transplantation.

[Thyroid cancers]. / Les cancers thyroïdiens.

During the last two decades, the incidence of thyroid cancer has doubled, mainly do to the early detection of small papillary tumors. However, mortality stayed stable (0.05/100.000). Well differentiated cancers (papillary and follicular) demonstrated a excellent survival prognosis (95 % at 30 years for the majority of the patients), factors of prognosis: age, size of the initial tumor, presence (or not) of distant metastases, lymph node involvement (only in patients 45 year or older). Surgery is the main treatment and should be with curative intent, hence the importance of a thorough preoperative work-up: sonography, needle aspiration cytology and MRI of cervicomediastinum for large tumors and/or suspected lymph nodes. Total thyroidectomy is mandatory, excepted for well selected patients with small (pT1) unilateral tumors under the age of 45. Central compartment lymph node clearance is advocated (but not evidence based) with presentation of the recurrent laryngeal nerves and of the parathyroids. Ablation of residual thyroid tissue (Iode 131) should be advocated for patients at high (or intermediary) risk of recurrence, only after multidisciplinary concertation. Unlimited follow-up checking the thyroglobulin serum local after the total thyroidectomy and radioactive ablation, the availability of recombinant rhTSH avoids the withdrawal of thyroid hormones (hypothyroid period). Anaplastic carcinomas are very aggressive, no therapeutic solution, excepted in some selected case for when radical surgery is possible (flap reconstruction) followed by chemoradiation. Calcitoninenia to detect and to follow medullary thyroid cancer after total thyroidectomy and lymph node clearance.