Long-lasting and controlled antioxidant property of immobilized gold nanoparticles for intelligent packaging.

The development of new packaging able to preserve sensitive biomolecules against oxidative stress is an important field. Several studies refer to antioxidant properties carried out by colloidal gold nanoparticles (AuNP). Herein, the purpose was to check whether this property is preserved when AuNP are immobilized on a glass support. After nanostructured film preparation, the physicochemical characterization proved that AuNP were well-individualized in the films with a high density of immobilization. Two radicals: ABTS•+ and DPPH• were used to investigate their antioxidant capacity. The results showed that immobilized AuNP had a preserved antioxidant capacity characterized by a different kinetic: more controlled and more prolonged but with the same efficiency (vs the same quantity of colloidal AuNP). The AuNP films demonstrated a capacity to prevent from degradation a molecule containing a thiol function. A 10-fold increase of N-acetylcysteine half-life was measured using the immobilized AuNP, highlighting the interest of the developed and adaptable support.

LR12-peptide quantitation in whole blood by RP-HPLC and intrinsic fluorescence detection: Validation and pharmacokinetic study.

A simple, sensitive, selective and robust HPLC method based on intrinsic fluorescence detection was developed for the quantitation of a dodecapeptide (designated as LR12), inhibitor of Triggering Receptor Expressed on Myeloid cells-1, in rat whole blood. Sample treatment was optimized using protein precipitation and solid-phase extraction. Chromatographic separation was carried out in a gradient mode using a core-shell C18 column (150 × 4.6 mm, 3.6 µm) with mobile phases of acetonitrile and water containing trifluoroacetic acid at 1.0 mL/min. The method was validated using methodology described by the US Food and Drug Administration guidelines for bioanalytical methods. Linearity was demonstrated within the 50-500 ng/mL range and the lower limit of quantitation was 50 ng/mL. Finally, a preliminary pharmacokinetic study after intraperitoneal injection of LR12 in rats was conducted to evaluate both LR12 monomer and its corresponding disulfide dimer, the main product of degradation. Beyond the fact that this paper describes the first fully validated method for LR12 analysis in blood samples, the approach followed here to optimize pre-analytical steps could be beneficial to develop HPLC and/or MS methods for other pharmaceutical peptides.

[Hydrogen sulfide: A promising therapy in neuroprotection following cardiac arrest?]. / Le sulfure d'hydrogène : une thérapeutique d'avenir dans la neuroprotection post-arrêt cardiorespiratoire ?

Each year, in France, the number of cardiac arrests is evaluated between 30,000 to 50,000. When a patient survives, he undergoes a post-resuscitation syndrome which can aggravate the injuries and for which nowadays, no medication is available. In some kinds of cardiac arrest, a hypothermia protocol can be applied with a need for monitoring because of the appearance of side effects. In this context, hydrogen sulfide, which is a gasotransmitter with numerous physiological and pharmacological properties, may be interesting. Indeed, its use could protect against oxidative, inflammatory and apoptotic troubles induced by the post-resuscitation syndrome. The implied biochemical mechanisms are adenosine triphosphate potassium channels activation and cytochrome c oxidase inhibition. This molecule can also induce a suspended animation state characterized by a metabolism decrease, which could give a delay for physicians to start a therapeutic monitoring. Thus, in spite of a modest and sometimes contradictory literature, this compound could become the first neuroprotective molecule in cardiac arrest.

[Genetic and environmental factors of asthma and allergy: Results of the EGEA study]. / Facteurs génétiques et environnementaux de l'asthme et de l'allergie: synthèse des résultats de l'étude EGEA.

INTRODUCTION AND METHODS: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles). RESULTS: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action. CONCLUSION: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution.

Impact of gold nanoparticle coating on redox homeostasis.

Gold nanoparticles (AuNP) hold great potential for biomedical applications. This study was aimed at examination of the effect of AuNP coating on the redox status of their environment. Two kinds of AuNP were tested, similar by shape and size, but with different surface coatings: either stabilized with citrate or functionalized with dihydrolipoic acid (Au@DHLA NP). Interestingly, whereas citrate-stabilized AuNP interact in vitro with reduced glutathione (GSH) and S-nitrosoglutathione, Au@DHLA NP do not interfere with both biomolecules. Albumin exhibits higher affinity toward citrate-stabilized AuNP than Au@DHLA NP, increasing their hydrodynamic diameter (8.0- and 1.3-fold, respectively). Furthermore, the AuNP coating affects also their internalization by macrophages (which was two fold higher for citrate-stabilized AuNP), following an exposure to a subtoxic NP concentration (10 nM, 80% viability). Citrate-stabilized AuNP were found to decrease the intracellular GSH level (ca. 20%), with no increase in reactive oxygen species production. Furthermore, these AuNP did not induce apoptosis (as shown by caspase-3 activity and nfkb2 transcription factor), and also did not activate gene expression related to oxidative stress (ncf1) and inflammatory response (tnfα). The present data highlight that the functionalization of AuNP with DHLA decreases their reactivity with biomolecules and cells, resulting in a promising medical platform.