Revisions to the international guidelines on the diagnosis and therapy of chronic urticaria

At the end of 2012, more than 300 participants discussed and agreed on the update of the international guidelines on urticaria at the 4th International Consensus Meeting (URTICARIA 2012). Currently, the recommendations are in the final process of international coordination. In preparation for the update, questions were prepared by an expert panel; this was followed by a systematic literature search. The questions and the resulting recommendations were discussed by the participants and decided upon in an open vote. Consensus was defined as at least 75% agreement. The updated guidelines will modify and improve the currently available guidelines in various areas, especially in therapy. For the treatment of chronic urticaria, the new algorithm recommends a three‐step process starting with a standard dose of a non‐sedating H1 antihistamine. If there is an insufficient treatment response, the dosage should be increased up to four times. In, therapy refractory patients, omalizumab, cyclosporine A, or montelukast are advised in the third step. Short‐term corticosteroid treatment for a maximum of 10 days may be considered. H2 antihistamines and dapsone, which were included in the previous version of the guidelines, are absent in the updated and revised version because of changes in the evidence level.     

Specialized Care of Women and Newborns Affected by Opioids With a CORE Team of Nurses

Staff on a mother–baby unit of a large suburban Level II facility identified the need to provide specialized nursing care to women affected by opioids. The manager of the unit recognized inconsistencies in care and frustration expressed by women and staff. She recruited a CORE (Champion for our Opiate patients using Respectful and Relevant Engagement and Education) group of staff nurses to care for these women. CORE nurses received specialized education and resources and served as the primary nurses for women admitted to the unit with a positive urine drug screening result or a history of drug use during pregnancy. Having a CORE team has brought a consistent approach when providing care to families affected by opioids.     

Mast cells protect from skin tumor development and limit tumor growth during cutaneous de novo carcinogenesis in a Kit‐dependent mouse model

Epidermal tumors belong to the most frequent type of neoplasms, and tumor‐associated accumulation of mast cells (MCs) has first been observed more than a century ago. Therefore, MCs have been implicated in tumor development and growth; however, the results regarding the role of MC in cutaneous de novo carcinogenesis are still controversially discussed. Here, we subjected MC‐deficient Kit^W/Kit^W?v mice to chemical skin carcinogenesis. Tumors were induced using the carcinogen 7,12‐dimethylbenz[a]‐anthracene and subsequent treatment with the tumor promoter 12‐tetradecanoyl‐phorbol‐13‐acetat. The treatment resulted in pronounced inflammatory cell infiltrates that were diminished in MC‐deficient animals. Unexpectedly, tumor development and growth was significantly increased in MC‐deficient Kit^W/Kit^W?v mice. The repair of their MC deficiency by local adoptive transfer of MCs normalized tumor incidence and growth. The recruitment of skin‐infiltrating immune cells, particularly of F4/80+ monocytes, Gr‐1+ granulocytes, B220+ B cells and CD8+ T lymphocytes, to sites of tumor development was, in part, also controlled by MCs. Recent evidence indicated the importance of local antitumor tissue immunity which prevents tumor development. These findings suggest a critical role for MCs in mediating these host antitumor immune responses in the skin.     

Membrane‐bound stem cell factor is the major but not only driver of fibroblast‐induced murine skin mast cell differentiation

The maintenance and modulation of cutaneous mast cell (MC) numbers is held to be important for skin immune responses to allergens and pathogens. The increase in MC numbers in the skin is achieved by proliferation and the differentiation of precursor to mature MCs. Fibroblast‐derived SCF is thought to be the major skin MC growth factor and it potently induces MC proliferation. The mechanisms of fibroblast‐induced skin MC differentiation, including the role of SCF, however, remain insufficiently characterized and understood. Using cocultures of immature murine MCs and fibroblasts, we found that the adhesion of immature MCs to fibroblasts via VCAM‐1 and α₄β₇ integrin is very important for subsequent differentiation, which is driven by fibroblast membrane‐bound SCF and additional fibroblast‐derived membrane‐bound signals. Thus, our results show that fibroblast‐induced MC differentiation is induced by direct cell–cell contact and involves both Kit‐dependent and Kit‐independent pathways. Our findings add to the understanding of how immature mast cells mature in murine skin and encourage further analyses of the underlying mechanisms, which may result in novel targets for the modulation of skin mast cell driven diseases.     

Mild heat treatments induce long-term changes in metabolites associated with energy metabolism in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Heat-induced hormesis, the beneficial effect of mild heat-induced stress, increases the average lifespan of many organisms. Yet little is known about the mechanisms underlying this effect. We used nuclear magnetic resonance spectroscopy to investigate the long-term effects of repeated mild heat treatments on the metabolome of male Drosophila melanogaster. 10 days after the heat treatment, metabolic aging appears to be slowed down, and a treatment response with 40 % higher levels of alanine and lactate and lower levels of aspartate and glutamate were measured. All treatment effects had disappeared 16 days later. Metabolic reprogramming has been associated with the life extending effects of dietary restriction. The metabolite changes induced by the hormetic treatment suggest that the positive effects might not be limited to the repair pathways induced, but that there also is a change in energy metabolism. A possible direct link between changes in energy metabolism and heat induced increase in Hsp70 expression is discussed.