Bioactive reagents used in mesotherapy for skin rejuvenation in vivo induce diverse physiological processes in human skin fibroblasts in vitro- a pilot study.

The promise of mesotherapy is maintenance and/or recovery of a youthful skin with a firm, bright and moisturized texture. Currently applied medications employ microinjections of hyaluronic acid, vitamins, minerals and amino acids into the superficial layer of the skin. However, the molecular and cellular processes underlying mesotherapy are still elusive. Here we analysed the effect of five distinct medication formulas on pivotal parameters involved in skin ageing, that is collagen expression, cell proliferation and morphological changes using normal human skin fibroblast cultures in vitro. Whereas in the presence of hyaluronic acid, NCTF135(®) and NCTF135HA(®) , cell proliferation was comparable to control cultures; however, with higher expression of collagen type-1, matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, addition of Soluvit(®) N and Meso-BK led to apoptosis and/or necrosis of human fibroblasts. The data indicate that bioactive reagents currently applied for skin rejuvenation elicit strikingly divergent physiological processes in human skin fibroblast in vitro.

[Contact dermatitis to permanent make up: manifestation of a pre-existing nickel allergy]. / Manifestation einer Nickelallergie als Kontaktdermatitis auf Permanent-Make-up.

During recent years demands for permanent make up and especially permanent lip liner is increasing not only in the USA but also in Germany. Adverse reactions to these products are almost unknown and not documented in literature. Declaration of contents and side effects are not required for tattoo colors, in contrast to the rules for medical treatments. Our patient developed inflammation and vesiculation within the area of tattooing three days after injection of a permanent lip liner. Treatment with steroids induced complete resolution of the lip liner-associated dermatitis. However, not only the effect of the lip liner was lost but also the natural color of her lip was partly destroyed by inflammation. Diagnostic allergy testing revealed strong delayed hypersensitivity to nickel and a mild patch test reaction to the permanent lip liner. Examination of the permanent make-up by mass spectrometry detected nickel in a concentration of 1.8 ppm. No allergic reaction could be seen when the purified red dye itself was tested. This patient with pre-existing nickel allergy developed an allergic contact dermatitis from the injection of a permanent lip liner contaminated with nickel.

DRO1, a gene down-regulated by oncogenes, mediates growth inhibition in colon and pancreatic cancer cells.

Neoplastic progression in human tissues appears to be paralleled by a series of genetic and epigenetic alterations. In human colorectal cancers, defect Wnt/beta-catenin/T-cell factor and RAS/RAF signaling pathways have a major contributing role in tumor initiation and progression. To date, much of the research on the consequences of beta-catenin activation has been focused on genes whose expression is believed to be activated by beta-catenin-associated T-cell factor-dependent transcription. Little is known about genes whose expression may be down-regulated secondary to beta-catenin activation. Using a subtractive suppression hybridization approach, we identified a gene with markedly decreased expression in rat RK3E epithelial cells neoplastically transformed by beta-catenin. Because expression of this gene was also down-regulated in RK3E transformed by several other oncogenes, the gene was named DRO1 for "down-regulated by oncogenes 1." Compared with corresponding normal tissues, DRO1 expression was found to be very reduced in colon and pancreatic cancer cell lines as well as in most colorectal cancer specimens. The predicted DRO1 protein contains three repetitive elements with significant similarity to the carboxyl-terminal regions of the predicted proteins from DRS/SRPX/ETX1 and SRPUL genes, suggesting the existence of a new protein family. Ectopic expression of DRO1 in neoplastically transformed RK3E or colorectal and pancreatic cancer cell lines lacking endogenous DRO1 expression resulted in substantial inhibition of growth properties. DRO1 was found to suppress anchorage independent growth and to sensitize cells to anoikis and CD95-induced apoptosis. Our findings suggest that inhibition of DRO1 expression may be an important event in the development of colorectal and pancreatic cancers.

Phenotypical and molecular profiling of the extraneuronal cholinergic system of the skin.

We present molecular and protein profiling of all acetylcholine receptors (ACh-R) in human scalp skin using PCR, in situ hybridization and double-labeling immunofluorescence. Within the epidermis, the nicotinic (n)ACh-R subunits, alpha3, alpha5, beta2, and beta4 were expressed in the basal cell layer (BCL) and in a single cell layer in the stratum granulosum; alpha9 was expressed in the basal and lower spinous layers. alpha7, alpha10, and beta1 were preferentially detected in the upper spinous and granular layers. Of the muscarinic (m)ACh-R, m1 and m4 were found in the suprabasal layers, whereas m2, m3, and m5 remained restricted to the lower layers. In the outer root sheath of the hair follicle, all ACh-R except alpha9, beta1, and m4 were found in the BCL whereas the alpha9, m4, and m5 ACh-R were restricted to the central cell layer. The alpha5, beta1, beta2, m1-m4 chains were strongly expressed in the inner root sheath. Undifferentiated sebocytes expressed the alpha3, alpha9, beta4, m3-m5 ACh-R whereas alpha7, beta2, beta4, m2, and m4 were found in mature sebocytes. In sweat glands, the alpha3*, alpha7, and m2-m5 ACh-R were most prominent in the myoepithelial cells whereas alpha9, beta2, m1, m3, and m4 ACh-R were present in the acinar cells. Taken together, our data result in a complete molecular map of the extraneuronal cholinergic system of the skin that may be translated into distinct functional reaction patterns.