published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Psychiatry / Doctoral / Doctor of Philosophy

published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

No description available.

This study involves a morphological and histological investigation of normal mouse tail skin and its response to crude coal tar and isoquinoline (a major constituent of coal tar). Mouse tail skin is unusual in that it undergoes both parakeratotic and orthokeratotic keratinization in adjacent sites. The former develops without a granular layer and resembles psoriasis, while the latter, with a granular layer, resembles normal human skin. Based on this property, mouse tail skin has frequently been used as a model for psoriasis but in spite of this, an integrated, detailed picture of its structure has not previously been described. This was achieved in this study by using a range of complementary techniques: light microscopy of embedded and frozen material, scanning and transmission electron microscopy, quantitative image analysis and autoradiography. Such a study may help to elucidate the mechanism of both orthokeratotic and parakeratotic keratinization. Coal tar has been used extensively in the treatment of psoriasis and is safe and effective. However, it is cosmetically unappealing, its mechanism of action is unknown and its efficacy varies with its composition which is extremely heterogeneous. Isoquinoline may significantly contribute to its anti-psoriatic properties. The mode of action of these substances as modifiers of the keratinization process may be clarified by studying their effects on the model. Both substances induced granular layer formation in previously parakeratotic areas, with concommitant development of an orthokeratotic stratum corneum, a desirable property in a potential anti-psoriatic. However, they also induced epidermal thickening and hyperkeratosis. The effects on the pilosebaceous unit were strikingly different: coal tar caused metaplasia of sebaceous glands with follicular hyperkeratosis and hair loss while isoquinoline caused sebaceous gland hypertrophy. Isoquinoline also caused far more epidermal irritation than coal tar, and caused damage to the basal lamina and dermal collagen. The irritant effects were modified to some extent by hydrocortisone cream but this also reduced granular layer induction. These studies suggest that isoquinoline may act on parakeratotic epidermis in a similar way to coal tar. It has the advantages of being a cleaner substance, with a more consistent action. However, its usefulness may be limited by its irritancy.

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