Cluster analysis of the dermal permeability and stratum corneum/solvent partitioning of ten chemicals in twenty-four chemical mixtures in porcine skin

Assumptions based on absorption from single solvent systems may be inappropriate for risk assessment when chemical mixtures are involved. We used K-means and hierarchical cluster analyses to identify clusters in stratum corneum partitioning and porcine skin permeability datasets that are distinct from each other based on mathematical indices of similarity and dissimilarity. Twenty four solvent systems consisting of combinations of water, ethanol, propylene glycol, methyl nicotinate and sodium lauryl sulphate were used with 10 solutes, including phenol, pnitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. Identifying the relationships between solvent systems that have similar effects on dermal absorption formed the bases for hypotheses generation. The determining influence of solvent polarity on the partitioning data structure supported the hypothesis that solvent polarity drives the partitioning of non-polar solutes. Solvent polarity could not be used to predict permeability because solvent effects on diffusivity masked the effects of partitioning on permeability. The consistent influence of the inclusion of propylene glycol in the solvent system supports the hypothesis that over saturation due to solvent evaporation has a marked effect on permeability. These results demonstrated the potential of using cluster analysis of large datasets to identify consistent solvent and chemical mixture effects

Visualizing the future we want: reconciling art, environment and development

This chapter explores how visual arts can communicate shared views and help to reconcile different understandings of desirable futures. I review experiences of the use of art to build shared understanding of environmental problems amongst different actors or stakeholders. I focus on the “landscape” as the area of interest and define landscapes and seascapes as the geographic space in which environmental outcomes are best perceived by people. Building consensus on desired future situations is one of the greatest challenges in confronting our current environmental dilemmas. A shared vision of a future scenario can provide a common goal for everyone. Visual techniques have become ubiquitous during recent decades, and we have grown accustomed to visual representations on social media, television, billboards, marketing and PowerPoint presentations in the classroom and at big international events. In many areas of human endeavour, people are using animated videos and short films to present ideas. I review experiences from my own activities which range from mural painting to providing focus for debate at global environmental conferences to participatory drawing of future scenarios with local communities in environmentally sensitive areas

Lipid synthesis inhibitors: Effect on epidermal lipid conformational changes and percutaneous permeation of levodopa

A combination of lipid synthesis inhibitors was used to enhance the in vitro and in vivo permeation of levodopa (LD) across rat epidermis, and their influence on epidermal lipids was investigated using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Rat epidermis was treated with ethanol and a combination of atorvastatin (750 μg/7 cm2), cerulenin (20 μg/7 cm2), and β-chloroalanine (600 μg/7 cm2) for sustaining the reduced content of epidermal cholesterol, fatty acids (as triglycerides), and ceramide (as sphingosine), respectively, in viable rat skin. This treatment resulted in significant (P<.05) synthesis inhibition of skin lipids up to 48 hours and 6-fold enhancement in the in vitro permeation of LD. The effective plasma concentration of LD was achieved within 1 hour and maintained over 48 hours after topical application to rat epidermis treated with a combination of these lipid synthesis inhibitors. ATR-FTIR studies of inhibitor(s)-treated rat epidermis revealed a significant decrease (P<.05) in peak height and area for both asymmetric and symmetric C−H stretching absorbances, suggesting extraction of lipids. However, an insignificant (P<.05) shift in the frequency of these peaks suggested no fluidization of epidermal lipids by lipid synthesis inhibitors. A direct correlation was observed between epidermal lipid synthesis inhibition, decrease in peak height or area, and percutaneous permeation of LD. Skin lipid synthesis inhibition by a combination of lipid synthesis inhibitors seems to offer a feasible approach for enhancing the transcutaneous delivery of LD