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Biomedical subjects

J LeClaire

Publications and source records attributed to J LeClaire.

3 recordsLinked to original sources

Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.

Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.

Animal Testing Alternatives↗

Industry experience with alternative methods.

L'OREAL has been using alternative methods for almost 30 years and this has led to their current widespread in-house use for evaluation of local effects in safety and efficacy. Alternative methods are used daily to assess eye and skin tolerance, phototoxicity, photoprotection, skin sensitization, percutaneous absorption and skin and hair care. For eye irritation, many years of in-house studies have enabled us to develop and to select the most reliable tests. New in vitro methods have also been developed to help to understand the ocular irritation mechanisms which underlie the irritative properties of new chemicals. In the field of skin irritation, L'OREAL's work has focused mainly on the wide possibilities offered by reconstructed human skins to evaluate the skin tolerance of cosmetics. Today we have managed to introduce Langerhans cells in reconstructed epidermis to develop an alternative to skin sensitization. Besides these in-house investigations either in research or in evaluation, our laboratories have contributed actively to multicentric studies to help the prevalidation/validation process in various fields. The alternative approach is now totally integrated into the safety evaluation strategy, and this allowed L'OREAL to totally ban animal testing on cosmetic products several years ago. In vitro alternatives are very powerful tools: they allow the study of fine mechanisms and the use of human cells. This overall 'in vitro' approach is a scientific, ethical and industrial breakthrough.

Animal Testing Alternatives↗

A new glare tester for clinical testing. Results comparing normal subjects and variously corrected aphakic patients.

A simple, inexpensive, readily available, easy-to-service clinical glare tester combines an audioviewer able-top projector with a series of specially made slides. Each slide supplies a constant glare source and a variable-contrast, central target. The device was evaluated on 161 normal subjects, 144 patients with cataracts, and 110 aphakic patients whose visual acuity was corrected with spectacles or intraocular lenses. Results showed that aphakic patients, irrespective of the mode of correction, were statistically more glare sensitive than normal phakic patients. Further results confirmed earlier studies that demonstrated that glare sensitivity also increased with age in normal eyes. Broad potential exists for using this method of glare testing in industry, transportation media, and medicolegal and and clinical ophthalmologic studies.

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