Proficiency testing for meropenem and piperacillin therapeutic drug monitoring : preliminary results from the Belgian Society on Infectiology and Clinical Microbiology Pharmacokinetic-Pharmacodynamic working group

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Interleukin-7 Regulates Adipose Tissue Mass and Insulin Sensitivity in High-Fat Diet-Fed Mice through Lymphocyte-Dependent and Independent Mechanisms

Although interleukin (IL)-7 is mostly known as a key regulator of lymphocyte homeostasis, we recently demonstrated that it also contributes to body weight regulation through a hypothalamic control. Previous studies have shown that IL-7 is produced by the human obese white adipose tissue (WAT) yet its potential role on WAT development and function in obesity remains unknown. Here, we first show that transgenic mice overexpressing IL-7 have reduced adipose tissue mass associated with glucose and insulin resistance. Moreover, in the high-fat diet (HFD)-induced obesity model, a single administration of IL-7 to C57BL/6 mice is sufficient to prevent HFD-induced WAT mass increase and glucose intolerance. This metabolic protective effect is accompanied by a significant decreased inflammation in WAT. In lymphocyte-deficient HFD-fed SCID mice, IL-7 injection still protects from WAT mass gain. However, IL-7-triggered resistance against WAT inflammation and glucose intolerance is lost in SCID mice. These results suggest that IL-7 regulates adipose tissue mass through a lymphocyte-independent mechanism while its protective role on glucose homeostasis would be relayed by immune cells that participate to WAT inflammation. Our observations establish a key role for IL-7 in the complex mechanisms by which immune mediators modulate metabolic functions

Conduite des essais cliniques de médicaments au niveau européen depuis la directive européenne essais cliniques. Revue des aspects réglementaires et pratiques dans différents pays

La directive essais cliniques avait pour but une harmonisation des législations afin de favoriser la cohérence du système européen et par la même l'attractivité de l'Europe en matière de recherche clinique tout en maintenant ou renforçant la protection des personnes qui acceptent d'y participer. La situation française en matière administrative était jusqu'à présent relativement favorable (étude à notifier avec déjà un seul comité d'éthique par étude), il est donc important de maintenir la compétitivité sur ces points sachant que sur d'autres points (délais de mise en place des conventions, recrutement, ...) la situation n'est pas à l'avantage de la France. À l'heure actuelle, la transposition de cette directive n'est pas encore totalement finalisée en droit français. La période pilote qui a été mise en place par l'Afssaps (Agence française de sécurité sanitaire des produits de santé) a permis d'établir sans délais les modalités de mise en place. Pour les CPP (Comités de Protection des Personnes), la situation est plus critique dans la mesure où beaucoup de points restent à établir (choix des membres, règlement intérieur, rapport CA/CE [autorités compétentes/comités d'éthique]...). L'atelier de Giens a permis de faire naître un certain nombre de propositions et souhaite par le biais du groupe de pilotage Afssaps / DGS (Direction Générale de la Santé) / LEEM (Les Entreprises du Médicament) continuer à contribuer à la mise en place d'un système efficace et protecteur pour les patients

The Conduct of Clinical Trials for Medicinal Products in Europe in the Light of the European Clinical Trials Directive. Review of Regulatory and Practical Aspects in the Different Countries

The purpose of the clinical trial guidelines is to harmonise legislation in order to ensure consistency within Europe and thereby promote Europe's attractiveness for clinical research while maintaining or improving the protection of subjects who agree to participate. The French administrative system has hitherto been relatively favourable (with simple notification to a single Ethics Committee per study); it is thus important to maintain competitiveness in these respects, given that, in other areas (the time it takes to establish agreements, recruitment, etc.), other countries have the advantage. At the moment, this Directive has not been entirely transposed into French law. The pilot period established by the Afssaps (French drug agency) has made it possible to determine very quickly how to set things up. For Ethics Committees, the situation is more critical in that many points remain that need to be finalised (selection of members, internal rules, Competent Authority/Ethics Committee relationship, etc.). The Giens workshop issued a number of proposals and it hopes, through the Afssaps)/DGS (French agency of health in government)/LEEM Steering Group (French pharmaceutical companies association), to be able to help establish an efficient system which also correctly protect the patient

A single injection of IL-7 protects SCID mice from HFD-induced obesity but not from glucose intolerance and WAT inflammation.

<p>(<b>A</b>) Body weight and perigonadal WAT and BAT masses of SCID male mice fed during 15 weeks with SD or HFD (white bars; PBS/SD, hatched bars; IL-7/SD, grey bars; PBS/HFD, black bars; IL-7/HFD); (<b>B</b>) Intraperitoneal glucose tolerance test at 6 weeks of diet feeding (white bars; PBS/SD, hatched bars; IL-7/SD, grey bars; PBS/HFD, black bars; IL-7/HFD); (<b>C</b>) Expression levels of macrophage (Emr1/F4-80, CD68) and inflammation (TNFα, MCP-1, Nos2) markers in perigonadal WAT, after 15 weeks of diet feeding, using real-time quantitative PCR (white bars; PBS/SD, hatched bars; IL-7/SD, grey bars; PBS/HFD, black bars; IL-7/HFD). Data are expressed as means ± SEM of 8 PBS/SD mice, 6 PBS/IL-7 mice, 3 PBS/HFD mice and 9 IL-7/PBS mice. ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001, HFD <i>vs</i> SD within the same injection group; ^*<i>p</i><0.05, ^***<i>p</i><0.001, IL-7 injection <i>vs</i> PBS injection in the same diet group.</p

A single injection of IL-7 reduces WAT inflammation during C57BL/6 HFD feeding.

<p>Real-time quantitative PCR analysis of the perigonadal white adipose tissue from C57BL/6 mice after a unique injection with PBS or IL-7, 16 weeks after SD or HFD feeding. (<b>A</b>) Expression levels of macrophages (Emr1/F4-80, CD68) and B-cells (CD19, CD20) markers; and (<b>B</b>) expression levels of inflammatory markers (TNFα, MCP-1 and Nos2). Data are expressed as means ± SEM of 7 to 9 mice per group (white bars; PBS/SD, hatched bars; IL-7/SD, grey bars; PBS/HFD, black bars; IL-7/HFD). ^#<i>p</i><0.05, ^##<i>p</i><0.01, ^###<i>p</i><0.001, HFD <i>vs</i> SD within the same injection group; ^*<i>p</i><0.05, ^**<i>p</i><0.01, ^***<i>p</i><0.001, IL-7 injection <i>vs</i> PBS injection within the same diet group.</p