Absorption and metabolism of the mycotoxin zearalenone and the growth promotor zeranol in Caco-2 cells in vitro

Scope: Zearalenone (ZEN) and α‐zearalanol (α‐ZAL, zeranol) were studied in differentiated Caco‐2 cells and in the Caco‐2 Millicell^® system in vitro to simulate their in vivo intestinal absorption and metabolism in humans. Methods and results: In addition to metabolic reduction/oxidation, extensive conjugation with glucuronic acid and sulfate of the parent compounds and their phase I metabolites was observed. The positional isomers of the glucuronides and sulfates were unambiguously identified: Sulfonation occurred specifically at the 14‐hydroxyl group, whereas glucuronidation was less specific and, in addition to the preferred 14‐hydroxyl group, involved the 16‐ and 7‐hydroxyl groups. Using the Caco‐2 Millicell^® system, an efficient transfer of the glucuronides and sulfates of ZEN and α‐ZAL and their phase I metabolites into both the basolateral and the apical compartment was observed after apical administration. The apparent permeability coefficients (P_app values) of ZEN, α‐ZAL and the ZEN metabolite α‐zearalenol were determined, using an initial apical concentration of 20 μM and a permeation time of 1 h. Conclusion: According to the P_app values, the three compounds are expected to be extensively and rapidly absorbed from the intestinal lumen in vivo and reach the portal blood both as aglycones and as glucuronide and sulfate conjugates in humans.     

Glucuronidation of zearalenone,zeranol and four metabolites in vitro: Formation of glucuronides by various microsomes and human UDP‐glucuronosyltransferase isoforms

Glucuronidation constitutes an important pathway in the phase II metabolism of the mycotoxin zearalenone (ZEN) and the growth promotor α‐zearalanol (α‐ZAL, zeranol), but the enzymology of their formation is yet unknown. In the present study, ZEN, α‐ZAL and four of their major phase I metabolites were glucuronidated in vitro using hepatic microsomes from steer, pig, rat and human, intestinal microsomes from humans, and eleven recombinant human UDP‐glucuronosyltransferases (UGTs). After assigning chemical structures to the various glucuronides by using previously published information, the enzymatic activities of the various microsomes and UGT isoforms were determined together with the patterns of glucuronides generated. All six compounds were good substrates for all microsomes studied. With very few exceptions, glucuronidation occurred preferentially at the sterically unhindered phenolic 14‐hydroxyl group. UGT1A1, 1A3 and 1A8 had the highest activities and gave rise to the phenolic glucuronide, whereas glucuronidation of the aliphatic hydroxyl group was mostly mediated by UGT2B7 with low activity. Based on these in vitro data, ZEN, α‐ZAL and their metabolites must be expected to be readily glucuronidated both in the liver and intestine as well as in other extrahepatic organs of humans and various animal species.     

Mastering the urbanization process. The urban questions of engineer August Mennes in the Antwerp agglomeration

Processes of urban expansion at the turn of the twentieth century have generally been described in terms of ‘regional planning’. However, in the Belgian context, and in Antwerp more specifically, the concept of the ‘agglomeration’ was put to the fore rather than the ‘region’, and ‘urbanization’ was a more common practice than ‘planning’. This paper shows how a ‘programme of urbanization’ centred on pertinent ‘urban questions’ shaped the contours of the Antwerp Agglomeration. In adopting this perspective of ‘programmatic urbanization’, the paper seeks to place the development of Antwerp extra muros within a different lineage, outside of the quest for comprehensive planning. Recomposing an eclectic catalogue of five pertinent ‘urban questions’, this paper investigates how and to which extent the Study Committee for the development of the Antwerp Agglomeration and its prominent engineer August Mennes, tried to master the urbanization process as it unfolded. Urbanization, then, is framed as a collective practice that generates positive agglomeration effects and surplus values that could not have been produced by individual actors. As such, the paper expands the understanding of urbanization from a random process of capital accumulation to a project that includes the building of social and cultural capital.     

Unraveling the Rewired Metabolism in Lung Cancer Using Quantitative NMR Metabolomics

Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown potential in cancer diagnosis. In this paper, the authors describe the alterations in the metabolic phenotype of lung cancer patients. In addition, we focus on the metabolic cooperation between tumor cells and healthy tissue. Furthermore, the authors discuss how metabolomics could improve the management of lung cancer patients.     

Enhancing traceability of wheat quality through the supply chain

With the growing global population, the need for food is expected to grow tremendously in the next few decades. One of the key tools to address such growing food demand is minimizing grain losses and optimizing food processing operations. Hence, several research studies are underway to reduce grain losses/degradation at the farm (upon harvest) and later during the milling and baking processes. However, less attention has been paid to changes in grain quality between harvest and milling. This paper aims to address this knowledge gap and discusses possible strategies for preserving grain quality (for Canadian wheat in particular) during unit operations at primary, process, or terminal elevators. To this end, the importance of wheat flour quality metrics is briefly described, followed by a discussion on the effect of grain properties on such quality parameters. This work also explores how drying, storage, blending, and cleaning, as some of the common post-harvest unit operations, could affect grain's end-product quality. Finally, an overview of the available techniques for grain quality monitoring is provided, followed by a discussion on existing gaps and potential solutions for quality traceability throughout the wheat supply chain.     

Feinstruktur und Hyperfeinstruktur von klinisch verwendeter Hydroxyethylstärke

Fine Structure and Hyperfine Structure of Clinically Applied Hydroxyethyl Starch. The Mark-Houwink-relationships for different samples of clinically used hydroxyethyl starches were established by multi-detection HPGPC. In combination with the degree of branching, the degrees of substitution DS and the molar substitution MS for the different molecular regions were measured by gas chromatographic methylation analysis. Within the molecular regions of non reducing anhydroglucose units, branching units and linear units we found characteristic differences. For hydroxyethyl starches which were prepared from enzymatically hydrolyzed waxy maize starch by α-Amylase, we found a significantly higher degree of branching than for samples prepared by acid hydrolysis. The clinical relevance of these results is discussed.