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Abstract: Byssochlamys species are responsible for spoilage and degradation of fruits and silages. Under specific conditions they are able to produce mycotoxins. The aim of this study was to evaluate the potential of 19 different strains of Byssochlamys nivea and Byssochlamys fulva to produce patulin in relation with the presence of two genes involved in the patulin biosynthesis pathways in the genome of these fungal strains. The strains were characterized by macroscopic, microscopic examinations, internal transcribed spacer (ITS) rRNA and β-tubulin fragment amplification and sequencing. All of the 8 B. nivea strains tested produced patulin. By contrast, none of the 11 strains of B. fulva produce this toxin. Two genes of the patulin biosynthetic pathway, a polyketide synthase (pks) and the isoepoxydon dehydrogenase (idh) were cloned from B. nivea. The deduced amino acid sequence of the polyketide synthase was 74% identical to the 6-methylsalicylic acid synthase gene of Penicillium griseofulvum and had the five functional domains characteristic of fungal type I polyketide synthases (beta-ketosynthase, acyltransferase, dehydratase, beta-ketoreductase and acyl carrier protein). The complete coding sequence of idh gene displayed after translation 88% of identity with P. griseofulvum IDH and 85% with P. expansum IDH, respectively. Both pks and idh messengers were strongly co-expressed during the production of 6-methylsalicylic acid and patulin. The presence of these genes was then investigated in the genome of B. nivea and B. fulva strains by PCR. All B. nivea strains possess the two genes, by contrast none of the B. fulva strains display these genes. The absence of 6-methylsalicylic acid and isoepoxydon dehydrogenase genes can explain the inability of B. fulva to produce patulin. In conclusion, B. fulva don''t seem to be responsible for the occurrence of patulin by lack of genes. [Copyright &y& Elsevier]

Abstract: The myco-estrogene zearalenone (ZEA) is a worldwide cereal contaminant, implicated in reproductive disorders in animals and humans. Intestinal cells constitute a first barrier to mycotoxins exposure, since they express membrane ABC transporters that may affect the bioavailability of food xenobiotics. In this study, we investigated the mechanisms involved in the transepithelial transfer of ZEA and its major metabolites α- and β-zearalenols (ZOLs), first using human intestinal Caco-2 cells. When exposed to ZEA, α-ZOL or β-ZOL either in the apical (AP) or basolateral (BL) compartment, cells showed asymmetry in the AP–BL and BL–AP transfer of mycotoxins. Metabolic inhibitors increased ZEA, α-ZOL and β-ZOL intracellular accumulation. Caco-2 cells apically exposed to ZEA produced metabolites (ZOLs and glucuronides) whose distribution between AP, BL and intracellular compartments was significantly modified by ABCCs inhibitor MK571. ABCB1-, ABCC1-, ABCC2 and ABCC3-transfected cells were used for studies of intracellular accumulation of ZEA, α-ZOL and β-ZOL with or without specific inhibitors, and for competitive studies using fluorescent substrates. The results showed that ZEA, α-ZOL and β-ZOL were substrates for ABCC2. ABCC1 was also involved in ZEA and α-ZOL transport, whereas ABCC3 only interacted with β-ZOL. These specific interactions suggest a role for ABCC1–3 transport proteins in zearalenone exposure and its resulting risk for human health. [Copyright &y& Elsevier]

Considerable efforts have been engaged in the design, synthesis and pharmacological characterization of radioligands for imaging the serotonin transporter, based on its implication in several neuropsychiatric diseases, such as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series, the fluoro derivative has been designed for positron emission tomography (PET). The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference compound have been synthesized. 5-[18F]Fluoro-6-nitroquipazine has been radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life) by nucleophilic aromatic substitution from the corresponding N-Boc protected 5-bromo- and 5-chloro-precursors using K[18F]F-K222 complex in DMSO by conventional heating (145 °C, 2 min) or microwave activation (50 W, 30–45 s), followed by removal of the protective group with TFA. Typically, 15–25 mCi (5.5–9.2 GBq) of 5-[18F]fluoro-6-nitroquipazine (1–2 Ci/μmol or 37–72 GBq/μmol) could be obtained in 70–80 min starting from a 550–650 mCi (20.3–24.0 GBq) aliquot of a cyclotron [18F]F− production batch (2.7–3.8% non decay-corrected yield based on the starting [18F]fluoride). Ex vivo studies (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5-[18F]fluoro-6-nitroquipazine ([18F]-1d) readily crossed the blood brain barrier and accumulated in the regions rich in 5-HT transporter (frontal- and posterial cortex, striata). However, the low accumulation of the tracer in the thalamus (rat and monkey) as well as the comparable displacement of the tracer observed with both citalopram, a -HT re-uptake inhibitor and maprotiline, a norepinephrine re-uptake inhibitor (rat), indicate that 5-[18F]fluoro-6-nitroquipazine ([18F]-1d) does not have the suggested potential for PET imaging of the serotin transporter (SERT). [Copyright &y& Elsevier]