The first 2(IB),3(IA)-heterodifunctionalized ß-cyclodextrin derivatives as artificial enzymes.

Novel 2,3-heterodisubstituted ß-cyclodextrin derivatives were designed as artificial enzymes to degrade chemical warfare agents. One of them reduced the acetylcholinesterase inhibitory potential by soman faster than its monosubstituted analog.

Functionalized cyclodextrins bearing an alpha nucleophile--a promising way to degrade nerve agents.

Organophosphorus nerve agents are irreversible inhibitors of acetylcholinesterase. Current treatment of nerve agent poisoning has limited efficacy and more efficient medical countermeasures need to be developed. A promising approach is to design chemical scavengers more stable during storage and less immunogenic than bioscavengers. Furthermore, they could be produced at lowest production costs. Cyclodextrins are attractive cyclic oligosaccharides that can be used to develop chemical scavengers of organophosphorus nerve agents. Their abilities to form inclusion and non-inclusion complexes with organic substrates are useful to trap chemical warfare agents. Selective introduction of an α-nucleophile residue on the secondary face of ß-cyclodextrin allowed to obtain supramolecular derivatives active against organophosphorus compounds. The degradation activity of these monosubstituted cyclodextrins was determined against paraoxon and chemical warfare agents. These tests showed that the structure of the scavengers mainly influences the interaction between the organophosphorus substrate, or its reaction products, and the cyclodextrin moiety. All the tested G-type agents were efficiently degraded. According to the binding modes of cyclosarin, some oligosaccharidic scavengers led to an enantioselective degradation of this nerve agent. These promising derivatives open the way to further investigations of new structural modifications to reach more sophisticated and efficient scavengers for prophylactic and curative medical applications.

Cell junction disruption after 36 h milk accumulation was associated with changes in mammary secretory tissue activity and dynamics in lactating dairy goats.

Milk stasis in the mammary gland is a situation that induces a reduction in milk yield and a change in its composition. Theses changes could be related to a decrease in the number and/or activity of secretory cells. Previous observations showed that a disruption of cell junctions is one of the early phenomena accompanying milk accumulation in the mammary gland. The aim of the present study was to investigate the local effect of 36 h milk accumulation on mammary cells activity, apoptosis and proliferation. We also studied the expression of cell junction proteins after 36 h of milk stasis. We observed a decrease in the quantity of milk produced after 36 h of milk stasis in goat. Lower milk lactose and protein yields were also observed, which was associated with a decrease in the transcripts of genes involved in synthesis of these constituents, such as alpha-lactalbumin and kappa-casein. Mammary gland apoptosis was more intensive than mammary cell proliferation after 36 h of milk accumulation. All these changes were associated with an up-regulation of E-cadherin protein and increase of its transcripts levels. It could suggest that these adjustments are made in order to limit losses of secretory cell number and activity.