Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure.

BACKGROUND: Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). METHODS: This study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89). RESULTS: MMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies. CONCLUSIONS: Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

The effect of topical pimecrolimus on inflammatory infiltrate in vulvar lichen sclerosus.

OBJECTIVE: Lichen sclerosus (LS) is a relatively common chronic inflammatory disorder of the skin and mucosal surfaces. STUDY DESIGN: A total of 29 women with histologically confirmed, active LS were recruited to this study with 2 aims. First, we evaluated the effectiveness of pimecrolimus treatment to LS not responding to conventional corticosteroid treatment. The second aim in this study was to provide information of in vivo effects of topical pimecrolimus in acute LS lesions, especially the inflammatory cell infiltration. RESULTS: In all, 25 of 29 women applied cream as recommended. After 2 months of treatment, 20 patients had reached partial or complete clinical remission. Histology showed decreased inflammatory lymphoid infiltrate with down-regulation of CD3(+) T cells, CD8(+) T cells, and CD57(+) natural killer cells. Also macrophage marker CD68 staining showed down-regulation. There was no change in CD20(+) B lymphocytes. CONCLUSION: We conclude that calcineurin inhibitors are an effective treatment for patients not responding to corticosteroid treatment.