Culture and drug biotransformation capacity of adult human keratinocytes from post-mortem skin.

The aim of this study was to analyse viability, growth, differentiation and drug metabolic capacity of cultured human keratinocytes obtained from post-mortem skin. Epidermal cells were prepared from 1-day post-mortem paired sun-exposed (outer) and sun-protected (inner) sites of the upper arm, of donors aged 47-80 years. The percentage of viable cells obtained from post-mortem skin was only slightly lower than that usually obtained for keratinocytes isolated from fresh skin, and no alterations of epidermal markers were noted. Keratinocytes isolated post-mortem from non-exposed skin had a higher viability (78 versus 73%), and a more active proliferation, while their attachment rate, keratin composition, lipid synthesis capacity and transglutaminase activity levels were similar to those of epidermal cells obtained from the sun-exposed skin. Keratinocytes isolated from post-mortem skin expressed various phase I and II activities at levels similar to those obtained with keratinocytes isolated from fresh skin while drug metabolizing enzyme activities were consistently higher in sun-exposed compared to sun-protected cells. The results support the conclusion that skin collected post-mortem can represent an alternative source of viable and functional epidermal cells, and that the functional changes that occur in adult keratinocytes habitually exposed to the sun, affect much more strongly the drug metabolism capacity than the expression of differentiation markers.

Cytotoxicity testing of beta-lactam antibiotics, non-steroidal anti-inflammatory drugs and sulfonamides in primary human keratinocyte cultures.

We have studied the cytotoxity to human keratinocytes of three main classes of drugs known to induce cutaneous adverse reactions, namely beta-lactam antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonamides, using the neutral red uptake as an endpoint. IC(50) values were determined for 21 drugs, after 20 hr of exposure and compared with those obtained with rat hepatocytes. NSAIDs were found to be more cytotoxic than beta-lactum antibiotics to human keratinocytes. Large variations in IC(50) values were obtained between molecules of a same class, as well as between keratinocyte cultures from different donors, especially for beta-lactum antibiotics. All NSAIDs and beta-lactam antibiotics tested were more cytotoxic to rat hepatocytes (1.6- to 27-fold). Both cell types were only slightly sensitive to sulfonamides, if at all.

[Hair dysplasia in oculo-dento-digital syndrome. Apropos of a mother-daughter case]. / Dysplasie pilaire au cours du syndrome oculo-dento-digital. A propos d'un cas mère-fille.

Oculo-dento-digital syndrome (SODD) as defined by Meyer-Schwickerath in 1957 is a rare entity (84 cases) which belongs to ectodermal dysplasias. It consists of: the characteristic features (long face, pinched nose); syndactyly; ocular, dental and bone abnormalities. This entity is usually transmitted on the autosomal dominant mode. We report two cases (a mother and daughter) with polymalformations which we classed as SODD. Furthermore, agenesis of lacrimal duct and genitourinary abnormalities were noted. The mother had a very particular complex hair shaft dysplasia (incomplete pili torti, "tiger tail" aspect, fractures) with alopecia since she was fifteen years old. The daughter's hair was normal at birth. In SODD, fine and sparse hair is often observed (44 p. 100). Only one patient had hair shaft investigation under polarized light: pili annulati and monilethrix were described but not found in our cases. These two reports incite to the systematic hair shaft study in SODD as other ectodermal dysplasia syndromes.