SAN-b-P4VP block copolymer synthesis by chain extension from RAFT-functional poly(4-vinylpyridine) in solution and in emulsion

Reversible addition fragmentation chain transfer (RAFT)-mediated polymerization was successfully applied for the synthesis of poly(4-vinylpyridine) (P4VP) polymers of predetermined molar mass and of low polydispersity index. These RAFT end-functionalized polymers were then used as macro-RAFT agents and further chain extended with an azeotropic mixture of styrene (STY) and acrylonitrile (AN) (63 mol% STY). Initially, these chain extension experiments were carried out in solution. In that case, the formation of the P4VP-b-SAN block copolymers clearly demonstrated the large fraction of chain end functionality in these RAFT-functional P4VP polymers. Proof of the formation of low molar mass P4VP-b-SAN block copolymer was obtained by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis. Gradient polymer elution chromatographic (GPEC) analysis confirmed successful formation of P4VP-b-SAN block copolymers. Block copolymer synthesis in emulsion was also investigated. The polymerization mediated by a RAFT-functional P4VP, macro-RAFT agent, was carried out as a semicontinuous process. The complete transformation of the P4VP starting block into P4VP-b-SAN block copolymer points to an efficient control of the polymerization in emulsion. This procedure leads to the formation of a colloidally stable latex. The results of GPEC analysis confirmed the successful block copolymer latex formation. © 2007 American Chemical Society.Articl

BDNF-TrkB signaling mediates cholinergic neuroplasticity in asthma

Background: Abnormal neuronal activity contributes to symptoms of allergic asthma, where increased cholinergic tone is observed. Neurotrophins such as brain-derived neurotrophic factor (BDNF) are target-derived neuronal growth factors and increasingly recognized as important in asthma. Here we hypothesized that there is an increased cholinergic neuronal density in asthmatic airways mediated by BDNF signaling via its receptor TrkB.Methods: Human bronchial biopsies were stained for the cholinergic marker vesicular acetylcholine transporter (VAChT). Human lung gene expression and single nucleotide polymorphisms (SNP) in neuroplasticity-related genes were compared between asthma and healthy patients. Wild-type (WT) and mutated TrkB knock-in mice (TrkBKI) with impaired BDNF signaling were chronically exposed to ovalbumin (OVA). Neuronal PGP9.5 and VAChT staining and airway narrowing in lung slices were assessed.Results: Compared to healthy subjects, bronchial biopsies from asthma patients showed a 1.6 fold higher VAChT+ area. Human lung transcriptome analysis revealed TrkB gene expression 1.5 fold higher in asthma versus healthy. Moreover, 5 SNPs in the BDNF gene and 1 SNP in the TrkB gene were associated with asthma. WT mice displayed a 2.0 fold increase in PGP9.5 and 1.8 fold increase in VAChT+ area, which were not observed in TrkBKI. Furthermore, airway hyperresponsiveness, as seen in WT mice, was not observed in TrkBKI.Conclusion: Our results indicate that in human asthma and in OVA exposed mice, an increased cholinergic nerve fiber density is present. The BDNF-TrkB signaling pathway might be involved in this neuroplasticity and genetic variation in both genes may contribute to asthma susceptibility