Publications by authors named "Eric Ezan"

Nanomaterials are present in a wide variety of health products, drugs and medical devices and their use is constantly increasing, varying in terms of diversity and quantity. The topic is vast because it covers nanodrugs, but also excipients (that includes varying proportions of NMs) and medical devices (with intended or not-intended (by-products of wear) nanoparticles). Although researchers in the field of nanomedicines in clinical research and industry push for clearer definitions and relevant regulations, the endeavor is challenging due to the enormous diversity of NMs in use and their specific properties.

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This Special Issue aims to provide an up-to-date investigation and reviews linked to antibody-based technologies for medical countermeasures and detection/diagnosis tools for toxins [...

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Inexpensive simple medical devices allowing fast and reliable counting of whole cells are of interest for diagnosis and treatment monitoring. Magnetic-based labs on a chip are one of the possibilities currently studied to address this issue. Giant magnetoresistance (GMR) sensors offer both great sensitivity and device integrability with microfluidics and electronics.

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Ligand-binding techniques such as immunoassays, the reference for clinical diagnosis, offer a wide range of innovative approaches based on signal DNA amplification, nanotechnologies or digital assays, which result in technologies with sensitivities more than 1000-times that of formats used 20 years ago. Providing that these technologies gain acceptance and translate into robust commercial platforms, we expect that several fields will be impacted in the near future, including the clinical diagnosis of cancer markers, the early detection of infectious diseases and the safety of biotherapeutics. Furthermore, the combination of these techniques with microfluidic systems will allow probing of biological diversity at the single cell level and will lead to the discovery of novel and rare biomarkers.

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Lethal and edema toxins are critical virulence factors of Bacillus anthracis. However, little is known about their in vivo dynamics of production during anthrax. In this study, we unraveled for the first time the in vivo kinetics of production of the toxin components EF (edema factor) and LF (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice.

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In the current context of international conflicts and localized terrorist actions, there is unfortunately a permanent threat of attacks with unconventional warfare agents. Among these, biological agents such as toxins, microorganisms, and viruses deserve particular attention owing to their ease of production and dissemination. Mass spectrometry (MS)-based techniques for the detection and quantification of biological agents have a decisive role to play for countermeasures in a scenario of biological attacks.

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Urine metabolomics is widely used for biomarker research in the fields of medicine and toxicology. As a consequence, characterization of the variations of the urine metabolome under basal conditions becomes critical in order to avoid confounding effects in cohort studies. Such physiological information is however very scarce in the literature and in metabolomics databases so far.

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Francisella tularensis is the causative agent of tularemia. Because some Francisella strains are very virulent, this species is considered by the Centers for Disease Control and Prevention to be a potential category A bioweapon. A mass spectrometry method to quickly and robustly distinguish between virulent and nonvirulent Francisella strains is desirable.

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Introduction: In the last decade, our increased knowledge of factors governing the pharmacokinetics and metabolism of biologics (recombinant therapeutic proteins) has driven, and will continue to support, biological engineering and the design of delivery systems for more efficient biologics. Further research in analytical methods for assessing their in vitro and/or in vivo metabolism will also support these developments.

Areas Covered: In this review we will discuss the main components affecting the metabolism of biologics, and try to demonstrate how novel analytical evaluations will facilitate their future development.

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According to the World Health Organization, food safety is an essential public health priority. In this context, we report a relevant proof of feasibility for the indirect specific detection of bacteria in food samples using unlabeled phage amplification coupled to ESI mass spectrometry analysis and illustrated with the model phage systems T4 and SPP1. High-resolving power mass spectrometry analysis (including bottom-up and top-down protein analysis) was used for the discovery of specific markers of phage infection.

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Bacillus anthracis is the causative bacteria of anthrax, an acute and often fatal disease in humans. The infectious agent, the spore, represents a real bioterrorism threat and its specific identification is crucial. However, because of the high genomic relatedness within the Bacillus cereus group, it is still a real challenge to identify B.

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Dietary sodium, the main determinant of the pharmacodynamic response to renin-angiotensin system blockade, influences the pharmacokinetics of various cardiovascular drugs. We compared the effect of contrasted sodium diets on the pharmacokinetics of single oral doses of 8 mg candesartan cilexetil, 160 mg valsartan, 10 mg ramipril, and 50 mg atenolol administered to 64 (16 per group) normotensive male subjects randomly assigned to sodium depletion (SD) or sodium repletion (SR) in a crossover study. Pharmacodynamic response was assessed as the increase in plasma renin concentration for renin-angiotensin system blockers and electrocardiographic changes in PR interval duration for atenolol.

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Among the growing number of therapeutic proteins on the market, there is an emergence of biotherapeutics designed from our comprehension of the physiological mechanisms responsible for their peripheral and tissue pharmacokinetics. Most of them have been optimized to increase their half-life through glycosylation engineering, polyethylene glycol conjugation or Fc fusion. However, our understanding of biological drug behaviors is still its infancy compared to the huge amount of data regarding small molecular weight drugs accumulated over half a century.

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We present here an analytical protocol for the sensitive, specific, and accurate absolute quantification of cetuximab, a human:murine chimeric monoclonal antibody, using mass spectrometry. Extraction from human serum is performed with micrometric magnetized beads, functionalized with soluble epidermal growth factor receptor (sEGFR), the pharmacological target of cetuximab. This specific immunocapture step allows sample purification and, in parallel, assessment of the antibody's biological potency.

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The specific forms of described protein biomarkers that occur in human blood are not yet fully established. Even though B-type natriuretic peptide (BNP) and N-terminal proBNP are now well known markers of heart failure and other cardiac disorders, several studies yielded highly controversial results reporting various truncated, multimerized or modified forms in human blood. Similar discrepancies were observed for other biomarkers also originating from proproteins, such as the apelin peptides.

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In two outbreaks of food-borne botulism in France, Clostridium botulinum type A was isolated and characterized from incriminated foods. Botulinum neurotoxin type A was detected in the patients' sera by mouse bioassay and in vitro endopeptidase assay with an immunocapture step and identification of the cleavage products by mass spectrometry.

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Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory.

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Rationale: Precise assessment of renal glomerular filtration rate (GFR) is essential for the early detection of chronic kidney disease. AcSDKP-NH(2), an analogue of the endogenous tetrapeptide AcSDKP, is not degraded in vivo and is freely filtered by the kidney and eliminated in urine; for that reason this analogue is an ideal candidate marker for the assessment of GRF after administration to humans. Proof-of-concept demonstration and lack of toxicity in animals have allowed an ongoing clinical study in which AcSDKP-NH(2) was administered intravenously at a dose of 100 µg and compared with currently available GFR markers.

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Bacillus anthracis is one of the most dangerous agents of the bioterrorism threat. We present here a sensitive immuno-liquid chromatography-tandem mass spectrometry (immuno-LC-MS/MS) approach to spore detection in complex environmental samples. It is based on the combined specificity and sensitivity of two techniques: immunocapture and targeted mass spectrometry.

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Apelin peptides were recently identified as endogenous ligands of the APJ receptor. It has been hypothesized that these peptides are initially provided to the newborn by nursing and might be involved in gastrointestinal tract development. As apelin peptides may have different effects on the APJ receptor as a function of their size, knowledge of their exact structure in early milk is essential to clarify their action in gastrointestinal tract development.

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Monitoring molecular dynamics of an organism upon stress is probably the best approach to decipher physiological mechanisms involved in the stress response. Quantitative analysis of proteins and metabolites is able to provide accurate information about molecular changes allowing the establishment of a range of more or less specific mechanisms, leading to the identification of major players in the considered pathways. Such tools have been successfully used to analyze the plant response to cadmium (Cd), a major pollutant capable of causing severe health issues as it accumulates in the food chain.

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