Significance or Scatter-Statistical Evaluation of Rapid Chloride Migration Test Results for Sprayable Cement Mortar.

In order to evaluate the influence of certain experimental or material-related conditions on results of the rapid chloride migration test (RCM test), statistical tests within and between samples are necessary. Thus, it needs to be clear which scatter a sample or a population of results is already subjected to without external influences due to the test method itself. So far, however, literature values for the appropriate statistical variable (coefficient of variation, CoV) explicitly valid for mortar or fine-grained concrete, e.g., for concrete repair, are missing. Therefore, we suggest a specific mortar CoV based on our own results of RCM tests performed on a cement-rich, sprayable mortar based on ordinary Portland cement. For the evaluation of external influences on a sample in comparison to a reference sample, we developed a significance criterion based on a statistical hypothesis test. The sensitivity and the reliability of this criterion is demonstrated on various results from RCM tests on mortar specimens, according to the test specifications and with deliberately chosen deviations from it. In addition, we point out the parameters included in the calculation of the rapid chloride migration coefficient that are the most sensitive to unintentional errors.

An important role of lymphatic vessel activation in limiting acute inflammation.

In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic vessels. Transgenic delivery of the lymphangiogenic factors VEGF-C and the VEGFR-3 specific ligand mouse VEGF-D significantly limited acute skin inflammation in both experimental models, with a strong reduction of dermal edema. Expression of VEGFR-3 by lymphatic endothelium was strongly down-regulated at the mRNA and protein level in acutely inflamed skin, and no VEGFR-3 expression was detectable on inflamed blood vessels and dermal macrophages. There was no major change of the inflammatory cell infiltrate or the composition of the inflammatory cytokine milieu in the inflamed skin of VEGF-C or VEGF-D transgenic mice. However, the increased network of lymphatic vessels in these mice significantly enhanced lymphatic drainage from the ear skin. These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation.

Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation.

The role of lymphangiogenesis in inflammation has remained unclear. To investigate the role of lymphatic versus blood vasculature in chronic skin inflammation, we inhibited vascular endothelial growth factor (VEGF) receptor (VEGFR) signaling by function-blocking antibodies in the established keratin 14 (K14)-VEGF-A transgenic (Tg) mouse model of chronic cutaneous inflammation. Although treatment with an anti-VEGFR-2 antibody inhibited skin inflammation, epidermal hyperplasia, inflammatory infiltration, and angiogenesis, systemic inhibition of VEGFR-3, surprisingly, increased inflammatory edema formation and inflammatory cell accumulation despite inhibition of lymphangiogenesis. Importantly, chronic Tg delivery of the lymphangiogenic factor VEGF-C to the skin of K14-VEGF-A mice completely inhibited development of chronic skin inflammation, epidermal hyperplasia and abnormal differentiation, and accumulation of CD8 T cells. Similar results were found after Tg delivery of mouse VEGF-D that only activates VEGFR-3 but not VEGFR-2. Moreover, intracutaneous injection of recombinant VEGF-C156S, which only activates VEGFR-3, significantly reduced inflammation. Although lymphatic drainage was inhibited in chronic skin inflammation, it was enhanced by Tg VEGF-C delivery. Together, these results reveal an unanticipated active role of lymphatic vessels in controlling chronic inflammation. Stimulation of functional lymphangiogenesis via VEGFR-3, in addition to antiangiogenic therapy, might therefore serve as a novel strategy to treat chronic inflammatory disorders of the skin and possibly also other organs.