Despite the importance of this disease there are currently limited therapeutic options indicating a need for effective, long-lasting treatment strategies with few side effects. The most recent discoveries regarding psoriasis pathogenesis, particularly our results regarding two cytokines -IL-22 and IL-20 – could prove to be the foundation for such therapies. Whereas IL-22 is mainly produced by activated T-cell sub-populations (Th22, Th1, Th17), monocytes,

dendritic cells and keratinocytes produce IL-20. Blood and lesional skin samples from psoriasis patients demonstrate high levels of IL-22 and IL-20. Interestingly, both cytokines act principally on keratinocytes and do not impact the immune system. Similar to the changes in the psoriasis epidermis these cytokines inhibit the R788 concentration terminal differentiation of keratinocytes although they simultaneously increase their innate defense, mobility, and the production buy S63845 of some chemokines. Some IL-22 effects are amplified by TNF-alpha, IL-17, and IFN-alpha. IL-22/IL-20

lends the reconstructed epidermis a psoriasis-like appearance with acanthosis, hypogranularity, and hyperkeratosis. In addition, mice that constitutively express high levels of IL-22 or IL-20 demonstrate a psoriasis-like appearance. A therapy counteracting IL-22 and IL-20 would be an innovative treatment with the potential for few side effects that would act on the final phase of psoriasis pathogenesis.”
“This study uses stereological techniques to examine body, internal gill and cardiovascular morphology of two larval amphibians, Pseudophryne bibronii and Crinia georgiana, to evaluate the roles of diffusive and convective gas exchange. Gosner stage 27 specimens were prepared for light microscopy and six parallel sections of equal distance taken through the body as well as a further six through the heart and internal gills. Body, internal

gill and heart volume as well as body and internal gill surface areas were determined. The harmonic mean distance across the internal gills was also measured and used to estimate oxygen diffusive conductance, DO2. The species were of similar body size and surface area, but Selleckchem IPI 145 the heart and internal gills were larger in P. bibronii, which may represent precursors for greater growth of the species beyond stage 27. The much larger surface area of the skin compared to the internal gills in both species suggests it is the main site for gas exchange, with the gills supplementing oxygen uptake. The sparse cutaneous capillary network suggests diffusion is the main oxygen transport mechanism across the skin and directly into deeper tissues. A numerical model that simplifies larval shape, and has an internal (axial vessels) and external oxygen source, confirms that diffusion is able to maintain tissue oxygen with limited convective input.