Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

<p>Abstract</p> <p>Background</p> <p>Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.</p> <p>Methods</p> <p>In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.</p> <p>Results</p> <p>In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.</p> <p>Conclusion</p> <p>An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00703651.</p

Novel Regulatory Mechanisms for Generation of the Soluble Leptin Receptor: Implications for Leptin Action

The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity.To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding.Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases

Fate and transfer of emerging contaminants coming from the health sector in soil and water compartments of the environment - Influence of the presence of metal cations.

L'objectif général de ce projet est d'apporter des données pertinentes sur le devenir de produits pharmaceutiques dans l'environnement, en particulier aux interfaces eau/sol, afin de mieux suivre les conséquences de leurs utilisations et de leurs rejets. A long terme, les enjeux concernent la protection de l'environnement et de la santé publique. Ces travaux portent sur la caractérisation des propriétés de rétention de cinq médicaments dans des sols calcaires de la région Champagne-Ardenne afin d'évaluer notamment leur potentiel transfert vers les milieux aquatiques. Différents paramètres ont été identifiés comme ayant une influence sur leur rétention. La rétention de l'enrofloxacine dépend fortement du pH et de la force ionique, celle du diclofénac des teneurs en CaCO3 et en matière organique des sols qui ont un effet antagoniste sur son adsorption, celle de la carbamazépine et du sulfaméthoxazole est faible sur un sol calcaire, et enfin la rétention du iopamidol est négligeable. Par ailleurs, l'influence des cations métalliques, polluants ubiquistes des sols, sur la rétention des médicaments a également été étudiée. Les expériences de co-adsorption ont montré que la présence de cuivre et de zinc influence significativement la rétention de l'enrofloxacine, conduisant à une augmentation des quantités adsorbées sur le sol via la formation d'un complexe ternaire de surface, et met ainsi en évidence l'importance de prendre en compte l'interaction des médicaments avec les métaux pour une meilleure compréhension de leur comportement dans les sols. Toutefois, aucune influence notable de la présence de cuivre sur la rétention des autres produits pharmaceutiques n'a été observée.The overall objective of this project is to provide a better knowledge of pharmaceuticals fate in the environment, more particularly at water/soil interfaces, in order to follow the consequences of their use and disposal. The long-term issues concern the protection of the environment and public health. This work focuses on the characterization of retention properties of five pharmaceuticals in calcareous soils of the Champagne-Ardenne region in order to evaluate their potential transfer to water compartments. Various parameters having an influence on their retention were identified. The retention of enrofloxacin is highly affected by pH and ionic strength, diclofenac retention by CaCO3 and organic matter contents of soils which have antagonistic effect on its adsorption, the retention of sulfamethoxazole and carbamazepine is low on a calcareous soil, and iopamidol adsorption is negligible. Moreover, the influence of metal cations, ubiquitous pollutants in soils, on pharmaceuticals retention was also studied. Co-adsorption experiments indicated that the presence of copper and zinc modifies significantly enrofloxacin retention, leading to an increase of adsorbed amounts on the soil via the formation of a ternary surface complex, thus highlighting the importance to take into account the interaction between metals and pharmaceuticals for a better understanding of their behavior in soils. However, no noticeable impact of the presence of copper on other pharmaceuticals retention has been noticed

Tours et la Loire : un spectacle éblouissant pour les officiers prussiens (1870-1871)

La guerre, la défaite, l’invasion renvoient à des faits d’ordre politique et militaire qui ont souvent été traités par les historiens. Mais ces événements, détestables par les malheurs collectifs et individuels qu’ils impliquent, sont aussi l’occasion pour des peuples, pour des hommes, de se côtoyer, se découvrir. Cette rencontre, on le comprend aisément, n’a que peu retenu l’attention des historiens jusqu’à une époque assez récente, où les différents aspects du quotidien de l’occupation nazi..

Adsorption and co-adsorption of diclofenac and Cu(II) on calcareous soils

International audiencePharmaceuticals are emerging contaminants and their presence in different compartments of the environment has been detected in many countries. In this study, laboratory batch experiments were conducted to characterize the adsorption of diclofenac, a widely used non-steroidal anti-inflammatory drug, on six calcareous soils. The adsorption of diclofenac was relatively low, which may lead to a risk of groundwater contamination and plant uptake. A correlation between the soil–water distribution coefficient Kd and soil characteristics has been highlighted. Indeed, diclofenac adsorption as a function of soil organic matter content (% OM) and Rt=% CaCO3/% OM was successfully described through a simple empirical model, indicating the importance of considering the inhibiting effect of CaCO3 on OM retention properties for a better assessment of diclofenac fate in the specific case of calcareous soils.The simultaneous co-adsorption of diclofenac and copper – a ubiquitous pollutant in the environment – at the water/soil interface, was also investigated. It appeared quite unexpectedly that copper did not have a significant influence on diclofenac retention