Clinical consequences related to a defective elimination of clobazam caused by homozygous mutated CYP2C19 allele

International audienc

Identification of the origin of infantile saturnism based on lead isotopic and elemental ratios

International audienc

Rethinking Alkylating(-Like) Agents for Solid Tumor Management

International audienceAlthough old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifunctional drug delivery systems, have shown promising results in potentiating anticancer activity while circumventing such hurdles. Furthermore, questioning of the old paradigm according to which nuclear DNA is the critical target of their anticancer activity has shed light on subcellular alternative and neglected targets that obviously participate in the mediation of cytotoxicity or resistance. Thus, rethinking of the use of these pivotal antineoplastic agents appears critical to improve clinical outcomes in the management of solid tumors

Eczéma de contact au diméthylfumarate : intérêt de l'analyse toxicologique

Date du colloque&nbsp;: 10/2009</p

Résultats complémentaires pour l'étude de stabilité des cannabinoïdes dans le sang : données d'un laboratoire sur le tétrahtydrocannabinol (THC) et son métabolite carboxylique (THC-COOH) dosés par HPLC/MS/MS

Date du colloque&nbsp;: 06/2009</p

Résultats complémentaires pour l'étude de stabilité des cannabinoïdes dans le sang : données d'un laboratoire sur le tétrahtydrocannabinol (THC) et son métabolite carboxylique (THC-COOH) dosés par HPLC/MS/MS

Date du colloque&nbsp;: 06/2009</p

Eczéma de contact au diméthylfumarate : intérêt de l'analyse toxicologique

Date du colloque&nbsp;: 10/2009</p

Genomic Organization and Expression of Iron Metabolism Genes in the Emerging Pathogenic Mold Scedosporium apiospermum

The ubiquitous mold Scedosporium apiospermum is increasingly recognized as an emerging pathogen, especially among patients with underlying disorders such as immunodeficiency or cystic fibrosis (CF). Indeed, it ranks the second among the filamentous fungi colonizing the respiratory tract of CF patients. However, our knowledge about virulence factors of this fungus is still limited. The role of iron-uptake systems may be critical for establishment of Scedosporium infections, notably in the iron-rich environment of the CF lung. Two main strategies are employed by fungi to efficiently acquire iron from their host or from their ecological niche: siderophore production and reductive iron assimilation (RIA) systems. The aim of this study was to assess the existence of orthologous genes involved in iron metabolism in the recently sequenced genome of S. apiospermum. At first, a tBLASTn analysis using A. fumigatus iron-related proteins as query revealed orthologs of almost all relevant loci in the S. apiospermum genome. Whereas the genes putatively involved in RIA were randomly distributed, siderophore biosynthesis and transport genes were organized in two clusters, each containing a non-ribosomal peptide synthetase (NRPS) whose orthologs in A. fumigatus have been described to catalyze hydroxamate siderophore synthesis. Nevertheless, comparative genomic analysis of siderophore-related clusters showed greater similarity between S. apiospermum and phylogenetically close molds than with Aspergillus species. The expression level of these genes was then evaluated by exposing conidia to iron starvation and iron excess. The expression of several orthologs of A. fumigatus genes involved in siderophore-based iron uptake or RIA was significantly induced during iron starvation, and conversely repressed in iron excess conditions. Altogether, these results indicate that S. apiospermum possesses the genetic information required for efficient and competitive iron uptake. They also suggest an important role of the siderophore production system in iron uptake by S. apiospermum

Therapeutic management of allergic diseases

Allergic diseases are characterized by the activation of inflammatory cells and by a massive release of mediators. The aim of this chapter was to describe succinctly the modes of action, indications, and side effects of the major antiallergic and antiasthmatic drugs. When considering the ideal pharmacokinetic characteristics of a drug, a poorly metabolized drug may confer a lower variability in plasma concentrations and metabolism-based drug interactions, although poorly metabolized drugs may be prone to transporter-based disposition and interactions. The ideal pharmacological properties of a drug include high binding affinity, high selectivity, and appropriate association and dissociation rates. Finally, from a patient perspective, the frequency and route of administration are important considerations for ease of use

Risks of addictive clay or kaolin consumption in pregnant women: Three cases reports

National audienceIn the literature, a chronic consumption of kaolin potentially exposes pregnant women to two risks: iron deficiency anemia/micronutrient deficiency and heavy metal poiso-ning. The consequences for the fetus and the newborn are still very little documented in the literature. We therefore report the cases of 3 pregnant women who consumed aluminum sili-cate, in the form of kaolin or coomba, as a cultural practice and Pica syndrome. The first case was documented by qualitative and quantitative analysis of a sample of the consumed kaolin. Quantitative analysis of the kaolin consumed by patient 1 showed a very high content of alumi-nium and a high content of copper, vadanium and lead. Only one patient out of the 3 presented an iron deficiency anemia with a normal blood lead level. The others had no repercussions. The Poison Control Center retrospectively followed up on these pregnant women to determine the progress of the delivery and the absence of complications in the newborn. These follow-ups indicated uncomplicated deliveries and normal birth weight. Despite the very high aluminum content of patient 1&#039;s sample, the risk of occurrence of chronic effects related to aluminum remains minimal given the low exceedance of the health reference values according to the European Food Safety Authority (EFSA). (C) 2023 Societe Francaise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved