A potential role for the secretogranin II-derived peptide EM66 in the hypothalamic regulation of feeding behaviour.

EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro-opiomelanocortin (POMC) and melanocortin-3 receptor mRNA levels and c-Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM66 does not alter the hypothalamic expression of neuropeptide Y (NPY), or that of its Y1 and Y5 receptors. A 3-month high-fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

[Advantages of corticosteroids in managing acute bacterial postoperative endophthalmitis]. / Intérêt des corticoïdes dans la prise en charge de l'endophtalmie postopératoire aiguë bactérienne.

Most studies show a trend toward a beneficial or at least neutral effect of associating corticosteroids and antibiotics. However, caution must be taken, with various factors considered: the type, virulence, and size of the inoculum, and the treatment chosen. Early intravitreal administration of 400 microg of dexamethasone seems to be beneficial in treating postoperative Staphylococcus epidermidis-related endophthalmitis. However, a large-scale prospective, randomized, controlled study is mandatory to gain evidence supporting steroid therapy in postoperative endophthalmitis.

[Incidence of infections dues to Escherichia coli strains producing extended spectrum betalactamase, in the Zou/Collines Hospital Centre (CHDZ/C) in Benin]. / Incidence d'infections liées à Escherichia coli producteur de bêta lactamase à spectre élargi au Centre hospitalier départemental du Zou et Collines au Bénin.

OBJECTIVES: Over a 6-month period, extended-spectrum betalactamase (ESBL)-producing isolates of Escherichia coli (EC) were collected from in-patients and their environment at the Zou-Collines Hospital Centre (CHDZ/C) in Benin. The aim of this study was to determine the incidence of ESBL and to describe their phenotypic susceptibility to antibiotics in a secondary hospital (500 beds) in Benin. METHODS: From 15 May to 15 November 2005, clinical informations and samples were collected from patients suspected to have nosocomial infections. The isolates were identified, tested for antimicrobial susceptibility and analysed for the presence of ESBL genes blaTEM and blaSHV by PCR. RESULTS: One hundred ninety-seven enterobacteria were isolated from the clinical samples of 342 patients, these isolates included 143 EC and 32/143 (22%) of these isolates produced ESBL. Forty-six EC were isolated from the environment and 7 (15%) of them produced ESBL. Except for Imipenem for which the difference was not significant, the isolates producing ESBL were more resistant to the other antibiotics (especially to third generation cephalosporins: Ceftriaxone, Cefotaxime, Ceftazidime (P<0.00001)) than non-ESBL producing isolates. Both ESBL genes blaSHV and blaTEM were identified in the EC ESBL strains from patient and from the environment. CONCLUSION: This study shows the presence of ESBL genes among EC in various wards of the CHDZ/C hospital proving that there is a need to implement a strict hospital infection control program and a regular surveillance of resistance to antimicrobial agents.

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.