The Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore.

Human α1-antitrypsin (AAT) is an abundant acute phase glycoprotein expressing anti-protease and immunomodulatory activities, and is used as a biopharmaceutical to treat patients with inherited AAT deficiency. The pleiotropic properties of AAT provide a rationale for using this therapy outside of inherited AAT deficiency. Therapy with AAT is administrated intravenously, yet the alternative routes are being considered.

Investigations of the relation between birth trauma and pelvic size in females from a medieval gravesite from Lübeck.

This study proposes that female pelvises showing no birth traumata may have had ideal child-bearing bone constitutions, differing significantly in size and shape from those with severe traumata, resulting in advantages during parturition. Based on this assumption, the female pelvises of a late medieval mass grave from Lübeck have been examined in terms of pelvic osteometric standards in obstetrics, morphological aspects, the degree of birth trauma lesions, and the possible effect of age at death on trauma mark severity. The results imply much wider pelvises (up to 1 cm) in the historical population and a shift in pelvic shape appearances from gynaecoid and platypelloid forms toward android and anthropoid shapes, compared with modern European populations.

Effects of photodynamic therapy evaluated in a novel three-dimensional squamous cell carcinoma organ construct of the skin.

Squamous cell carcinoma (SCC) of the skin is a malignant neoplasm that occurs in all ethnic groups primarily due to chronic sun exposure and constitutes a major health problem worldwide. Novel therapies for SCC are in development but as yet no in vitro models capable of screening these therapies and their mechanism of action before proceeding to clinical trials in human subjects have emerged. For this reason we have developed and characterized a novel three-dimensional human SCC construct and validated it using photodynamic therapy (PDT), a well-established modality for treating in situ SCCs.

Xenobiotics in vitro: the influence of L-cystine, pantothenat, and miliacin on metabolic and proliferative capacity of keratinocytes.

To investigate the effect of cell growth-stimulating agents on human epidermal keratinocytes, we exposed monolayers of normal human keratinocytes derived from foreskin to different concentrations of the amino acid L-cystine, the member of the vitamin B family D-pantothenat, the phytosterol miliacin, and a combination thereof in keratinocyte growth medium. As a test system for the metabolic capacity, we used the activity of mitochondrial deyhdrogenases as measured by XTT, and for the cell proliferation, we determined the BrdU-uptake. The additives, active ingredients of the hair growth drug PRIORIN, were added in the presence of fully supplemented keratinocyte growth medium or a deficient medium without L-cystine, L-methionine, L-histidin, D-pantothenat, epidermal growth factor, and bovine pituary gland extract.

Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro.

Retinoic acid exerts a variety of effects on gene transcription that regulate growth, differentiation, and inflammation in normal and neoplastic skin cells. Because there is a lack of information regarding the influence of metabolic transformation of retinoids on their pharmacologic effects in skin, we have analyzed the functional activity of all-trans-, 9-cis-, and 13-cis-retinoic acid and their 4-oxo-metabolites in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts using gene and protein expression profiling techniques, including cDNA microarrays, two-dimensional gel electrophoresis, and MALDI-MS. It was previously thought that the 4-oxo-metabolites of RA are inert catabolic end-products but our results indicate instead that they display strong and isomer-specific transcriptional regulatory activity in both NHEKs and dermal fibroblasts.