Dear Colleagues.

This letter is to summarize news from the last ETRS Board Meeting as well as to comment on a very interesting paper which may be of some importance for clinicians and scientists who deal with impaired wound healing.

The last ETRS Board Meeting was held in Southampton on 3 February 2007. The main purpose of this Board Meeting was to organize and look at the venue of the 17th Annual Meeting of the European Tissue Repair Society (ETRS), which will take place from Tuesday 26 September to Friday 28 September 2007 in the very beautiful Macdonald Botley Park Hotel, Golf and Country Club, Southampton, UK.

This meeting is organized by the current Congress President Professor Raj Mani and his scientific committee as well as a local organizing committee. This venue is highly appropriate to support a scientific meeting and to make scientists feel very comfortable, a prerequisite for fruitful personal and scientific interactions. The ETRS Board will support Dr Raj Mani in his initiative to attract excellent scientists and clinicians to this ETRS Annual Meeting and to focus on the support of young investigators and students. Accordingly, the registration fees for young investigators and students will be reduced, and Young Investigator Awards, Poster Prizes, similar to Pisa, should further encourage the presentation of excellent work in Southampton. Professor Raj Mani has put together a scientific programme in which he has managed to balance basic science and its translation to the clinical daily routine. With the ETRS 2007 Meeting in Southampton he has managed to generate a platform also for health economists who are all engaged in the difficult act of translating science into practice.

Southampton, with an area population of 1.2 million, is located in the south of England. It is very well connected by air to UK and Europe, by rail (one hour from London Waterloo) and road (the motorway bisects the city). Southampton city is surrounded by miles of the New Forest vibrant with colours and wildlife that is exceptionally attractive in September. The Isle of Wight to the south offers a very pleasant family day for those who love sailing as well as those who just like to tour casually. There is an impressive history around within driving distance (Romsey, Winchester, Portsmouth). Information about these and many more attractive places will be found on the site of the 17th Annual Meeting of the European Tissue Repair Society, <www.etrs2007soton.com>.

On behalf of the ETRS Board, I am very much looking forward to seeing you in Southampton to continue our discussions initiated in Pisa last year.

Let me now shortly summarize a very interesting letter in Nature by Nicholas Houstis, Evan D. Rosen and Eric S. Lander (Nature 440: 944–948, 2006). These scientists have elegantly proven that reactive oxygen species have a causal role in multiple forms of insulin resistance. As you know, insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings as for clinicians and scientists dealing with impaired wound healing in type 2 diabetes (neurotrophic ulcers, chronic venous leg ulcers or ulcers due to arteriosclerosis). Little is known about why insulin resistance occurs in so many contexts. The authors of the above mentioned manuscript report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the proinflammatory cytokine tumour-necrosis factor-_ and the other with a glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models. The authors show in the study that insulin resistance resulting from the treatment of 3T3-L1 adipocytes with either the inflammatory cytokine tumour-necrosis factor- a or the glucocorticoid dexamethasone. Both dexamethasone an TNF-a are well-validated experimental models of insulin resistance, and both have physiological relevance in vivo. TNF-a signals through a cell-surface cytokine receptor, whereas dexamethasone signals through a nuclear hormone receptor. Cultured 3T3-L1 adipocytes exposed to TNF-a or dexamethasone become insulin resistant within several days as assessed by the ability of insulin to stimulate glucose uptake. Six different treatments designed to alter the ROS levels, including two small molecules and transgenes, all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese insulin resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. These findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.

Given the fact that chronic venous leg ulcers are characterized by increased levels of pro-inflammatory cytokines such as TNF-a, and on the other hand characterized by a hostile pro-oxidant microenvironment, it may well be that the subcutaneous tissue develops locally an insulin resistance and a dramatic change in its endocrine activities crucial for physiological wound healing. The interaction of the restoration tissue with the subcutaneous tissue is significantly disturbed as observed by the lipodermatosclerosis, a hallmark for impaired wound healing. This may be of further pathological importance, as the subcutaneous tissue and its specific endocrine environment represent a very important niche for mesenchymal stem cells.

And with these thoughts, I would like to wish you all the best, again I am very much looking forward to meeting you in Southampton.

Karin Scharffetter-Kochanek
President