Bibliothek

Notizen: The article begins with some observations about the trend towards demutualization of mutual and co-operative businesses, and then presents a case study of one, rather dramatic, example: the attempted takeover of Europe’s largest consumer co-operative, CWS. It draws on original research into the takeover bid to provide a summary of what happened and when, and then asks some important questions about whether consumer co-operatives are inherently less efficient than PLCs in the retail sector; whether they can make themselves safe from takeover; if they do survive, how they can justify their existence as member-owned businesses; and whether there are alternative forms such as worker or multi-stakeholder ownership that can achieve the broad aims of the co-operative sector more effectively. It concludes that if CWS and similar organizations are to survive they must integrate the two aspects of a co-operative—the business and the association—and take seriously the opportunities and responsibilities that being a member-owned organization implies.

Notizen: Background  The skin represents an accessible somatic tissue for therapeutic gene transfer. The superficial lipophilic layer of the skin, the stratum corneum, however, constitutes a major obstacle to the cutaneous delivery of charged macromolecules such as DNA.Objectives  To determine whether silicon-based microneedles, microfabricated via a novel isotropic etching/BOSCH reaction process, could generate microchannels in the skin of sufficient dimensions to facilitate access of lipid : polycation : pDNA (LPD) nonviral gene therapy vectors.Methods  Scanning electron microscopy was used to visualize the microconduits created in heat-separated human epidermal sheets after application of the microneedles. Following confirmation of particle size and particle surface charge by photon correlation spectrocopy and microelectrophoresis, respectively, the diffusion of fluorescent polystyrene nanospheres and LPD complexes through heat-separated human epidermal sheets was determined in vitro using a Franz-type diffusion cell. In-vitro cell culture with quantification by flow cytometry was used to determine gene expression in human keratinocytes (HaCaT cells).Results  The diffusion of 100 nm diameter fluorescent polystyrene nanospheres, used as a readily quantifiable predictive model for LPD complexes, through epidermal sheets was significantly enhanced following membrane treatment with microneedles. The delivery of LPD complexes either into or through the membrane microchannels was also demonstrated. In both cases considerable interaction between the particles and the epidermal sheet was observed. In-vitro cell culture was used to confirm that LPD complexes mediated efficient reporter gene expression in human keratinocytes in culture when formulated at the appropriate surface charge.Conclusions  These studies demonstrate the utility of silicon microneedles in cutaneous gene delivery. Further studies are required to elucidate fully the influence of the physicochemical characteristics of gene therapy vectors, e.g. particle diameter and surface charge, on their diffusion through microchannels and to quantify gene expression in vivo.