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Purpose: S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia. Experimental Design:Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH). Results: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals. Conclusion: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.

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Agriculture surplus were used as substrates to synthesize gamma-aminobutyric acid (GABA) by Lactobacillus plantarum DSM19463 for the manufacture of a functional beverage or as a novel application for dermatological purposes. Dilution of the grape must to 1 or 4% (w/v) of total carbohydrates favored higher cell yield and synthesis of GABA with respect to whey milk. Optimal conditions for synthesizing GABA in grape must were: initial pH 6.0, initial cell density of Log 7.0 cfu/mL, and addition of 18.4 mM L-glutamate. L. plantarum DSM19463 synthesized 4.83 mM of GABA during fermentation at 30 degrees C for 72 h. The fermented grape must also contain various levels of niacin, free minerals, and polyphenols, and Log 10.0 cfu/g of viable cells of L. plantarum DSM19463. Freeze dried preparation of grape must was applied to the SkinEthic(R) Reconstructed Human Epidermis or multi-layer human skin model (FT-skin tissue). The effect on transcriptional regulation of human beta-defensin-2 (HBD-2), hyaluronan synthase (HAS1), filaggrin (FGR), and involucrin genes was assayed through RT-PCR. Compared to GABA used as pure chemical compound, the up-regulation HBD-2 was similar while the effect on the expression of HAS1 and FGR genes was higher.

Results indicate that Utipro creates a protective physical barrier on intestinal epithelial cells in vitro which reduces the settling of E. coli reservoirs. These results constitute the first step in the demonstration of the efficacy of Utipro to prevent urinary tract infections. Further research is needed in in vivo models and clinical trials.