Barrier functions of human skin: a holistic view.

The fascinating topic of skin barrier continues to engage researchers from diverse disciplines both in academia and industry. Much of the information on the basic biology of barrier formation, its ontogeny as well as repair and homeostasis comes from studies on animal models. A smaller number of human studies have validated the usefulness of animal models, while highlighting some essential differences. We submit that the human skin barrier is unique in several ways, as much due to our adaptive ability as our control over the environment (macro and micro) that none of the other species have exerted. The human skin is not only exposed to the greatest variations of environment due to our phenomenal mobility but also to the largest number of xenobiotics, both chemical and microbial, resulting from human activity. In this overview, we attempt to evaluate the interdependent relation of skin barriers to environmental stressors hoping to raise interest in some of the lesser known or neglected aspects of human skin barriers as they relate to skin health and dysfunctions.

Cosmetics. A dermatologist looks to the future: promises and problems.

The skin-care industry has created myriad new products to meet the needs of an aging population. Novel "bioactive" ingredients are derived from the sea, the earth, and the plant kingdom. Popular ingredients include Chinese herbs, vitamins, minerals, antioxidants, enzymes, hormones, and a multitude of "naturals". For academic medicine, this avalanche of new products poses the task of establishing international safety standards for determining how much product efficacy is science-based and how much is marketing hype.

The Mexican hairless dog as a model for assessing the comedolytic and morphogenic activity of retinoids.

The skin of the Mexican hairless dog is covered with comedones, and this animal therefore provides a potentially useful model to assess the comedolytic activity of topical anti-acne drugs. We treated an animal with three different formulations of tretinoin for a 14-week period, and all produced a similar clinical response. There was a striking reduction in the number of comedones, and the skin became lighter and more uniform in colour. Histological changes were similar to those reported in humans treated with tretinoin, but a novel finding was incomplete neogenesis of hair follicles. We suggest that the Mexican hairless dog may be a useful model for screening novel molecules for retinoid activity.

Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients.

Renal transplant recipients experience a greatly increased frequency of neoplastic skin lesions, including aggressive squamous cell carcinomas. Recent reports suggest that high doses of systemic retinoids may exert a chemotherapeutic and chemoprophylactic effect. Similarly, topical retinoid, especially tretinoin, has also been shown to be anti-tumoragenic in various settings. Because of the serious toxicity of high-dose systemic retinoid, a protocol was developed that combined topical tretinoin with low-dose etretinate (10 mg daily) for the treatment of frequently occurring dysplastic skin lesions in renal transplant recipients. Seven patients elected to receive combined tretinoin and etretinate therapy, and 4 were treated with tretinoin alone. Clinical evaluations were performed monthly. By 3 months of therapy, 9 of 11 patients exhibited at least a 25% decrease in the number of neoplastic growths. After 6 months, 6 of 8 evaluable patients, including 2 of 3 individuals receiving tretinoin alone, exhibited at least a 50% decrease. Three of 4 patients on the combined regimen and 2 of 3 receiving tretinoin alone for at least 9 months, exhibited a significant decrease in the rate of development of new squamous cell cancers. At the start of treatment, epidermal specimens were almost completely devoid of Langerhans cells (CD1+ cells). Their density increased greatly and in proportion to the duration of therapy. Long term topical tretinoin with or without low-dose oral etretinate seems to be an effective regimen to suppress the development of new tumors and to reduce the numbers of existing lesions in renal transplant recipients.

Human assay for identifying substances which induce non-allergic contact urticaria: the NICU-test.

The problems of non-immunologic contact urticariogens are addressed from various points of view. A new test for evaluating substances which may cause non-immunologic contact urticaria in humans, the NICU test, is introduced. Characteristic data of widely known contact urticariogens are given.

Age differences in poison ivy dermatitis.

In both man and animals, cell-mediated immunity diminishes with advanced age. Because poison ivy is a very common allergy, we evaluated age-associated differences in the contact allergic reaction to Rhus. Oleoresin patch tests were applied to two age cohorts (18-25 versus 65-84) each of 14 healthy white subjects. In the elderly, the allergic reaction developed more slowly, the inflammatory response at peak was greatly diminished and the dermatitis lasted longer and seemed to be more pruritic.

Identification of systemic phototoxic drugs by human intradermal assay.

An improved method is presented for the detection of systemically administered photosensitizing drugs in humans. Test agents were injected intradermally in physiologic saline and then exposed to broad spectrum radiation from a Xenon solar simulator. Several clinically recognized photosensitizers were identified by this technique. The activating spectrum depended on the test drug. Sulfonamides and vinblastin were activated by sunburning erythemic radiation (UV-B), while tetracyclines, nalidixic acid and phenothiazines by near UV (UV-A), and chlorothiazide by both. It is suggested that intradermal phototesting offers a means of verifying the phototoxic potential of agents suspected clinically of provoking a photosensitivity eruption.

Ultraviolet phototherapy and photochemotherapy of acne vulgaris.

The therapeutic value of various ultraviolet treatments was assessed in patients with moderately severe papulopustular acne. The results did not verify the common belief that ultraviolet radiation is highly beneficial. In no instance was the comedo count appreciably reduced. Modest improvement was observed with sunburn rays (UV-B) and slightly more with the combination of long ultraviolet radiation (UV-A) and UV-B. UV-A alone had the least effect. Photosensitization with coal tar and UV-A greatly aggravated acne and was notably comedogenic. Photosensitization with methoxsalen (8-methoxypsoralen) applied topically was neither harmful nor helpful.

Role of microorganisms in dandruff.

The role of microorganisms in dandruff was studied, by suppressing individually and then collectively the three major components of the scalp microflora. The effect on dandruff was assessed subjectively by clinical grading and objectively by the corneocyte count. No effect on dandruff was demonstrated when scalp organisms were suppressed. In the second group of experiments, dandruff was suppressed by selenium sulfide shampooling and the effect of continued suppression of Pityrosporum with topically applied amphotericin was measured. According to our criteria, dandruff returned to pretreatment levels, despite continued suppression of Pityrosporum. The studies demonstrate that the increased number of scalp microorganisms found in dandruff occurs as a secondary event to increased nutrients and that scalp organisms play no primary role in the pathogenesis of dandruff.

Effect of hydrogenated fat on the plasma cholesterol and triglyceride levels of man.

A group of 33 adult males was fed for 21 days a formula diet that supplied 38 per cent of their calories as fat. The fatty acid composition of the diet was 25 per cent saturates, 16 per cent polyunsaturates and 58 per cent monounsaturates. All of the unsaturated acids were in the cis configuration. The subjects were then divided into two groups. One group of 17 men continued on the same diet. In the diet of the remaining subjects, 80 per cent of the dietary fat was replaced with a hydrogenated fat. Over 60 per cent of the monounstaurated acids and approximately one-half of the polyunsaturated acids of the diet of this latter group were in the trans configuration. Except for the presence or absence of trans acids, the fatty acid intakes of the two groups were the same. Over the 4-week period that the two diets were consumed, the group receiving the hydrogenated fat showed no change in plasma cholesterol or triglyceride levels relative to the subjects consuming the unhydrogenated fat. It is concluded that the effect of a hydrogenated fat on blood lipid level is determined by its fatty acid composition and this effect is not altered by the isomeric form of the unsaturated acids.