The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells.

INTRODUCTION: High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. METHODS AND RESULTS: Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. CONCLUSIONS: Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process

Development of a New Type of Prolonged Release Hydrocodone Formulation Based on Egalet® ADPREM Technology Using In Vivo–In Vitro Correlation

A novel abuse deterrent, prolonged release tablet formulation of Hydrocodone for once-daily dosing has been developed, based on the novel proprietary Egalet® ADPREM technology. The tablet is an injection molded polymer system consisting of an erodible matrix in which the Active Pharmaceutical Ingredient (API), such as Hydrocodone, is dispersed. The matrix is partly covered with a water-impermeable, non-erodible shell which leaves both ends of the cylindrical tablet exposed to erosion by the gastrointestinal (GI) fluid. In vivo–in vitro correlation (IVIVC) was initiated and validated with three formulations. A good internal predictability was observed for the three formulations. How the changing conditions in the GI tract influenced in vivo performance of an erosion based product was discussed. The validated IVIVC could be used to optimize the tablet formulation and to obtain a desired profile. In addition, this technique could help to establish the dissolution limits in which a certainty of bioequivalence is calculated. Based on this validated level A IVIVC, dissolution can be used as surrogate of bioequivalence for development, but also scale up post approval changes

Caligus elongatus and other sea lice of the genus Caligus as parasites of farmed salmonids: A review

Accepted manuscript version, licensed CC BY-NC-ND 4.0. This review was prompted by reports of unusually large numbers of sea lice tentatively identified as Caligus elongatus infesting farmed salmon in northern Norway. Following a brief introduction to the sea lice problem in salmonid aquaculture, the review is divided into a further eight sections. The first is a review of existing information on the life cycle and behaviour of Caligus spp. The second is a description of the morphology of different stages in the life cycle of C. elongatus. The third describes the effects of caligid infestations on salmonid hosts. The fourth reviews information on the geographical distributions and host preferences of the six species of Caligus reported from farmed salmonids in different parts of the world: C. elongatus, C. curtus, C. clemensi, C. rogercresseyi, C. teres and C. orientalis. The fifth section describes interactions between farmed and wild fish and the sixth presents information on the genetics of C. elongatus. A section reviewing the different methods used to control sea lice infestations follows. The eighth section discusses the predicted effects of climate change and invasive host species on the distribution and occurrence of caligid copepods, and the ninth gives conclusions and recommendations on how to further investigate the infestation that prompted this review. These include the confirmation of the identity of the caligid causing the problem, confirmation of the genotype involved and a study of the vertical distribution in the water column of the infective stages