Prevention of 3-methylcholanthrene-induced skin tumors in mice by simultaneous application of 13-cis-retinoic acid and retinyl palmitate (vitamin A palmitate).

Abdel-Galil AM, Wrba H, El-Mofty MM.

Exp Pathol. 1984;25(2):97-102.

Two retinoids (13-cis-retinoic acid and retinyl palmitate ) have been shown to exert a good preventive effect in chemically induced papillomas and carcinomas of the skin in female Swiss mice; this effect was investigated over a period of 23 weeks. The tumors were induced by repeated topical application of 3-methylcholanthrene (0.3% MCA, dissolved in acetone; 14 applications). Retinyl palmitate (RP; 6 mg in 0.1 ml acetone/mouse; 10 applications) and 13-cis-retinoic acid (RA; 3 mg in 0.1 ml acetone/mouse; 10 applications) were also administered topically for the 3rd to 9th week from the start of the experiment. This investigation gave evidence for the fact that both the retinoids did not only inhibit the development of skin papillomas but had also a marked effect on skin carcinomas.

Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal injury.

Araneo BA, Ryu SY, Barton S, Daynes RA Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.

J Surg Res 1995 Aug;59(2):250-62

Progressive ischemia and necrosis of the skin following thermal injury are reduced by postburn administration of the steroid hormone dehydroepiandrosterone (DHEA). Thermally injured animals were provided with a subcutaneous injection of DHEA, or a related species of steroid hormone, at various times after burning. During the 96 hr following administration of the scald burn, tissue necrosis was closely monitored. Subcutaneous administration of DHEA at approximately 1 mg/kg/day achieved optimal protection against the development of progressive dermal ischemia. DHEA, 17 alpha-hydroxy-pregnenelone, 16 alpha-bromo-DHEA, and androstenediol each demonstrated, a similar level of protection. Other forms of steroids, including DHEA sulfate, androstenedione, 17 beta-estradiol, or dihydrotestosterone, exhibited no protective effect under the conditions tested. Additionally, intervention therapy with DHEA could be initiated up to 4 hr, but not 6 hr, after burn without a marked reduction in therapeutic benefit. Examination of the microvasculature of thermally injured dorsal skin suggested that postburn intervention with DHEA, either directly or indirectly, maintained a normal architecture in most of the dermal capillaries and venules within burn-exposed tissue. These findings suggest that systemic intervention therapy of burn patients with DHEA or a similar acting steroid hormone may be useful in preventing the progressive tissue destruction caused by progressive ischemia.

Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). Influence of the application time point.

Bangha E, Elsner P, Kistler GS. Department of Dermatology, University of Zurich, Switzerland.

Dermatology 1997;195(3):248-52

BACKGROUND: In a previous study, we reported a significant and dose-dependent suppression of UV-induced erythema in human skin by a topically applied melatonin preparation.

OBJECTIVE: The present double-blind randomized study was designed to examine the influence of the application time point of topical melatonin on this antierythema effect.

METHODS: Defined small areas on the lower back of 20 volunteers were treated with 0.6 mg/cm2 melatonin dissolved in a nanocolloid gel carrier either 15 min before or 1, 30 or 240 min after UV irradiation with twice the individual minimal erythema dose delivered by a Multiport Solar UV Simulator (UVA and UVB). The erythemata induced were evaluated by visual scoring and chromametry 24 h after irradiation.

RESULTS: Treatment of the skin with melatonin 15 min before UV irradiation proved to almost completely suppress the development of an UV-induced erythema. In contrast, no significant protective effects of melatonin were observed when it was applied after UV irradiation.

CONCLUSION: Topically applied melatonin has a clear-cut protective effect against UV-induced erythema. Free radical scavenging of UV-generated hydroxyl radicals and interference with the arachidonic acid metabolism are possible mechanisms of the melatonin action.

Botulinum toxin A in the therapy of mimic facial lines.

Becker-Wegerich P, Rauch L, Ruzicka T. Department of Dermatology, Heinrich Heine University Dusseldorf, Germany. Petra.Becker-Wegerich@uni-duesseldorf.de

Clin Exp Dermatol 2001 Oct;26(7):619-30

In aesthetic medicine, many different methods of skin rejuvenation are available. At the end of the 1980s, the neurotoxin Botulinum toxin A (BT-A) led to a revolution in aesthetic-corrective dermatology for the treatment of mimic facial wrinkles. The toxin is produced by Clostridium botulinum and causes a reversible, selective muscle relaxation that leads to a temporary flattening of the mechanical part of wrinkling without the stigmata of invasive surgery. After two decades of experience in different medical disciplines, there has been remarkable clinical development and progress in research, the identification of new botulinum toxin serotypes, and also innovation in indications and combined modalities. These lead to new and interesting questions. BT-A offers the experienced, critical dermatologist a time-saving, effective, cosmetically satisfactory, non-invasive treatment for mimic facial wrinkles and neck and decollete lines, with only minor side effects. Dermatologists should have a profound anatomical knowledge and should be able to perform all injection techniques to meet the needs of ever more demanding patients and to ensure optimization of patient satisfaction. The following review summarizes the historical development and the mechanism of action of both frequently and rarely used injection techniques with BT-A for the treatment of wrinkles and lines of the upper face, neck and decollete, and gives an update of different experiences encountered.

Sex hormones and skin collagen content in postmenopausal women.

Brincat M, Moniz CF, Studd JW, Darby AJ, Magos A, Cooper D.

Br Med J (Clin Res Ed) 1983 Nov 5;287(6402):1337-8

Skin biopsy specimens were taken from 29 postmenopausal women who had not been given hormone replacement therapy and from 26 women who had been treated with oestrogen and testosterone implants for two to 10 years. The mean hydroxyproline content and therefore the mean collagen content in the skin was found to be 48% greater in the treated than the untreated women, who were matched for age. This difference was significant (p less than 0.01). The implication of this finding is that oestrogen or testosterone, or both, prevents the decrease in skin collagen content that occurs with aging and protects skin in the same way as it protects bone in postmenopausal women.

Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled.

Chapellier B, Mark M, Messaddeq N, Calleja C, Warot X, Brocard J, Gerard C, Li M, Metzger D, Ghyselinck NB, Chambon P. Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, College de France, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France.

EMBO J. 2002 Jul 1;21(13):3402-13.

To investigate the roles of retinoic acid (RA) receptors (RARs) in the physiology of epidermis that does not express RAR beta, conditional spatio-temporally controlled somatic mutagenesis was used to selectively ablate RAR alpha in keratinocytes of RAR gamma-null mice. Keratinocyte proliferation was maintained in adult mouse epidermis lacking both RAR alpha and RAR gamma, as well as in RAR beta-null mice. All RAR-mediated signalling pathways are therefore dispensable in epidermis for homeostatic keratinocyte renewal. However, topical treatment of mouse skin with selective retinoids indicated that RXR/RAR gamma heterodimers, in which RXR transcriptional activity was subordinated to that of its RAR gamma partner, were required for retinoid-induced epidermal hyperplasia, whereas RXR homodimers and RXR/RAR alpha heterodimers were not involved. RA-induced keratinocyte proliferation was studied in mutant mice in which RXR alpha, RXR alpha and RAR alpha, RAR gamma, or RXR alpha and RAR gamma genes were specifically disrupted in either basal or suprabasal keratinocytes. We demonstrate that the topical retinoid signal is transduced by RXR alpha/RAR gamma heterodimers in suprabasal keratinocytes, which, in turn, stimulate proliferation of basal keratinocytes via a paracrine signal that may be heparin-binding EGF-like growth factor.

Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.

Darr D, Dunston S, Faust H, Pinnell S. North Carolina Biotechnology Center, Raleigh, N.C., USA.

Acta Derm Venereol. 1996 Jul;76(4):264-8.

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection. Protective effects of topical antioxidants in humans.

Dreher F, Maibach H. Department of Dermatology, University of California, San Francisco, Calif., USA.

Curr Probl Dermatol. 2001;29:157-64.

Human studies have convincingly demonstrated pronounced photoprotective effects of 'natural' and synthetic antioxidants when applied topically before UVR exposure. Particularly with respect to UVB-induced skin damage such as erythema formation, the photoprotective effects of antioxidants are significant when applied in distinct mixtures in appropriate vehicles. Topical application of such combinations may result in a sustained antioxidant capacity of the skin, possibly due to antioxidant synergisms. And, since UVA-induced skin alterations are believed to be largely determined by oxidative processes [26], topical administration of antioxidants might be particularly promising [27, 28]. In fact, topical application of antioxidants or antioxidant mixtures resulted in a remarkable increase in the minimal dose to induce immediate pigment darkening after UVA exposure [18, 23] and diminished the severity of UVA-induced photodermatoses [22] in humans. In conclusion, regular application of skin care products containing antioxidants may be of the utmost benefit in efficiently preparing our skin against exogenous oxidative stressors occurring during daily life. Furthermore, sunscreening agents may also benefit from combination with antioxidants resulting in increased safety and efficacy of such photoprotective products [11, 29]. Does estrogen prevent skin aging?: Results from the first national health and nutrition examination survey (NHANES I)

Dunn L.B.; Damesyn M.; Moore A.A.; Reuben D.B.; Greendale G.A. USA

Archives of Dermatology (USA), 1997, 133/3 (339-342)

Objective: To evaluate the relation between noncontraceptive estrogen use and skin wrinkling, dryness, and atrophy. Design: Cross-sectional analysis of a national probability sample-based cohort study. Setting: Multiple community sites throughout the United States. Participants: Postmenopausal women (n=3875) aged 40 years and older at baseline.

Measurements: Skin conditions (wrinkling, dryness, and atrophy) were ascertained using a uniform clinical examination by trained dermatology resident physicians. Self-reported use of estrogen before the baseline examination, sunlight exposure, and smoking history were obtained by standardized interview. Body mass index, a measure of weight in kilograms divided by the square of the height in meters, was evaluated in uniform examination clothing.

Results: Mean (plus or minusSD) age of the participants was 61.6 (plus or minus9.0) years and mean (plus or minusSD) number of years since menopause was 15.6 (plus or minus9.4). Most were white (83.7%), the remainder being African American (15.9%) or another race (0.4%). Atrophy was present in 499 (16.2%), dry skin in 1132 (36.2%), and wrinkled skin in 880 women (28.2%). The prevalence of all 3 skin conditions was lower in African American women compared with white women. Information on hormone use was available for 3403 participants (88%). Among all women, after adjustment for age, body mass index, and sunlight exposure, estrogen use was associated with a statistically significant decrease in the likelihood of senile dry skin (odds ratio, 0.76; 95% confidence interval, 0.60-0.97). The odds of wrinkling were substantially lower in estrogen users, adjusted for age, body mass index, and sun exposure (odds ratio, 0.68; 95% confidence interval, 0.52-0.89) and additionally for smoking (odds ratio, 0.67; 95% confidence interval, 0.44-1.01). In multivariable models, estrogen use was not associated with skin atrophy.

Conclusion: These results strongly suggest that estrogen use prevents dry skin and skin wrinkling, thus extending the potential benefits of postmenopausal estrogen therapy to include protection against selected age- and menopause-associated dermatologic conditions.

[Melatonin in dermatology. Experimental and clinical aspects] [Article in German]

Fischer T, Wigger-Alberti W, Elsner P. Klinik fur Hautkrankheiten, Friedrich-Schiller-Universitat Jena.

Hautarzt 1999 Jan;50(1):5-11

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Serum melatonin levels exhibit a circadian rhythm with low levels during the day, rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin participates in the regulation of several physiological processes such as seasonal biological rhythm, daily sleep induction, aging and modulation of immunobiological defence reactions. Furthermore, melatonin has a highly lipophilic molecular structure facilitating penetration of cell membranes and serving as an extra- and intracellular free radical scavenger. Melatonin seems to quench mainly hydroxyl radicals, the most damaging of all free radicals. Melatonin may play a role in the etiology and treatment of several dermatoses e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin on hair growth is another aspect. Topical application of melatonin inhibits the development of UV-erythema. Penetration through skin after topical application and oral bioavailability auxit further investigations on the pharmacokinetic and pharmacodynamic actions of melatonin.

Pathophysiology of premature skin aging induced by ultraviolet light.

Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ. Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0609, USA.

N Engl J Med. 1997 Nov 13;337(20):1419-28.

BACKGROUND: Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging.

METHODS: We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis.

RESULTS: A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin.

CONCLUSIONS: Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.

Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage.

Fitzpatrick RE, Rostan EF. Dermatology Associates of San Diego County, Inc. 92024, USA. fitzskin@pacbell.net

Dermatol Surg. 2002 Mar;28(3):231-6.

BACKGROUND: Aging of the population, in particular the "baby boomers," has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex.

OBJECTIVE: The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement.

METHODS: Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient.

RESULTS: A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement.

CONCLUSION: This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.

Effects of dietary retinyl palmitate or 13-cis-retinoic acid on the promotion of tumors in mouse skin.

Gensler HL, Watson RR, Moriguchi S, Bowden GT.

Cancer Res. 1987 Feb 15;47(4):967-70.

The present study was designed to determine the effects of dietary 13-cis-retinoic acid and retinyl palmitate on mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Female CD-1 mice were initiated with 150 nmol of 7,12-dimethylbenz(a)anthracene and promoted twice weekly with 8 nmol of TPA. Diets supplemented with retinyl palmitate to yield 60,000 or 200,000 IU or 700,000 for 5 wk followed by 350,000 IU per kg of diet (700,000/350,000) fed to mice during tumor promotion resulted in 9%, 37%, and 65% inhibition of the papilloma yield, respectively, at 21 wk of promotion. Although topical applications of 13-cis-retinoic acid have been almost as effective as retinoic acid in preventing the appearance of mouse skin tumors, dietary 13-cis-retinoic acid at 200,000 or 700,000 IU per kg of diet resulted in no reduction in papilloma yield but did result in a dose-dependent decrease in the tumor burden (weight of tumors per mouse). Therefore, dietary retinyl palmitate yielded a dose-dependent inhibition of the number and weight of tumors promoted by TPA, whereas dietary 13-cis-retinoic acid resulted in a decrease in weight but not in number of tumors promoted by TPA. Aging of human skin: review of a mechanistic model and first experimental data.

Giacomoni PU, Declercq L, Hellemans L, Maes D. Clinique Research Laboratories, Melville, NY, USA. pgiacomo@estee.com

IUBMB Life. 2000 Apr;49(4):259-63.

The physical, chemical, and biochemical factors that accelerate skin aging have been proposed to activate a self-maintained microinflammatory process, one of the expected end results of which is an imbalance in the turnover of macromolecules in the dermis. Surface peroxides are recognized as controllable factors of skin aging, and their accumulation is attributed to environmentally induced impairment of defense enzymes. Topical application of antioxidants decreases the rate at which skin elasticity and skin thickness are modified.

Dehydroepiandrosterone and two structural analogs inhibit 12-O-tetradecanoylphorbol-13-acetate stimulation of prostaglandin E2 content in mouse skin.

Hastings LA, Pashko LL, Lewbart ML, Schwartz AG. Department of Microbiology, Temple University Medical School, Philadelphia, PA 19140.

Carcinogenesis 1988 Jun;9(6):1099-102

Dehydroepiandrosterone, a naturally occurring adrenal steroid, is a highly effective tumor chemopreventive agent in laboratory mice and rats, inhibiting spontaneous breast cancer and chemically induced tumors of the lung, colon, skin, liver and thyroid. Dehydroepiandrosterone blocks three processes that have been implicated in experimental tumorigenesis: (i) carcinogen activation through the mixed-function oxidases, (ii) 12-O-tetradecanoylphorbol-13-acetate stimulation of superoxide anion production in neutrophils, and (iii) 12-O-tetradecanoylphorbol-13-acetate stimulation of [3H]thymidine incorporation in mouse epidermis. All of these effects of dehydroepiandrosterone very likely result from glucose-6-phosphate dehydrogenase inhibition and a lowering of the NADPH cellular pool. It is now reported that oral administration of dehydroepiandrosterone (0.2% in the diet) for two weeks inhibits the stimulation in prostaglandin E2 content in mouse epidermis produced by topical application of 12-O-tetradecanoylphorbol-13-acetate. Two synthetic steroids, 16 alpha-fluoro-5-androsten-17-one and 16 alpha-fluoro-5 alpha-androstan-17-one, which are more potent inhibitors of the above three processes in tumorigenesis and are also more effective than dehydroepiandrosterone in inhibiting skin papilloma development in the mouse, are more active in suppressing prostaglandin E2 induction by 12-O-tetradecanoyl-phorbol-13-acetate. These two structural analogs, which also lack specific side-effects associated with dehydroepiandrosterone treatment, may find application as cancer chemopreventive drugs in humans.

Inhibitory effect of glycolic acid on ultraviolet-induced skin tumorigenesis in SKH-1 hairless mice and its mechanism of action.

Hong JT, Kim EJ, Ahn KS, Jung KM, Yun YP, Park YK, Lee SH. Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Korea.

Mol Carcinog 2001 Jul;31(3):152-60

Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been used commonly as a cosmetic ingredient since it was discovered to have photoprotective and anti-inflammatory effects and antioxidant effects on ultraviolet (UV)B-irradiated skin. Little is known, however, about the functional role of glycolic acid on UV-induced skin tumorigenesis. In the present study, we examined the effect of glycolic acid on UV (UVA + UVB)-induced skin tumorigenesis and assessed several significant contributing factors in SKH-1 hairless mice. Inbred hairless female mice (15 animals/group) were irradiated for 5 d/wk at a total dose of 74.85 J/cm(2) UVA and 2.44 J/cm(2) UVB for 22 wk. Glycolic acid was applied topically twice a week at a dose of 8 mg/cm(2) immediately after UV irradiation. Glycolic acid reduced UV-induced skin tumor development. The protective effect of glycolic acid was a 20% reduction of skin tumor incidence, a 55% reduction of tumor multiplicity (average number of tumors/mouse), and a 47% decrease in the number of large tumors (larger than 2 mm). Glycolic acid also delayed the first appearance of tumor formation by about 3 wk. The inhibitory effect of glycolic acid on UV-induced tumor development was accompanied by decreased expression of the following UV-induced cell-cycle regulatory proteins: proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E, and the associated subunits cyclin-dependent kinase 2 (cdk2) and cdk4. In addition, the expression of p38 kinase, jun N-terminal kinase (JNK), and mitogen-activated protein kinase kinase (MEK) also was lower in UV + glycolic acid-treated skin compared with expression in UV-irradiated skin. Moreover, transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB) activation was significantly lower in UV + glycolic acid-treated skin compared with activation in UV-irradiated skin. These results show that glycolic acid reduced UV-induced skin tumor development. The decreased expression of the cell-cycle regulatory proteins PCNA, cyclin D1, cyclin E, cdk2, and cdk4 and the signal mediators JNK, p38 kinase, and MEK may play a significant role in the inhibitory effect of glycolic acid on UV-induced skin tumor development. In addition, the inhibition of activation of transcription factors AP-1 and NF-kappaB could contribute significantly to the inhibitory effect of glycolic acid. Copyright 2001 Wiley-Liss, Inc.

The effect of glycolic acid on cultured human skin fibroblasts: cell proliferative effect and increased collagen synthesis.

Kim SJ, Won YH Department of Dermatology, Chonnam University Research Institute of Medical Science, Chonnam National University Medical School, Kwangju, Korea.

J Dermatol 1998 Feb;25(2):85-9

Glycolic acid peeling is known to improve photoaging processes such as wrinkling and roughness, but this effect has not been clearly defined, even though functional activation of fibroblasts has been suggested. The study was aimed to determine the effects of glycolic acid and malic acid (AHA: alpha hydroxy acid) on cultured dermal fibroblasts. Whether it directly increases cell proliferation may be an important factor influencing the production of extracellular matrix such as type I collagen. Cultured human skin fibroblasts were treated for 24 hours with glycolic acid and malic acid at different concentrations (10(-4), 10(-5), 10(-6) M), and cell proliferation was measured by MTT assay. Then quantitative analysis of collagen synthesis was performed by PICP (Procollagen Type I C-peptide) enzyme immunoassay and radioisotope (3H-proline) labeled collagen assay. The results showed increased cell proliferation and collagen production in response to glycolic acid in a dose dependent manner. The range of cell proliferation and collagen production were significantly higher with glycolic acid treatment than with malic acid or control. It as suggested that the favorable effects of glycolic acid treatment on aging skin were mediated by increased cell proliferation in addition to functional activation of fibroblasts.

Double-blind clinical study reveals synergistic action between alpha-hydroxy acid and betamethasone lotions towards topical treatment of scalp psoriasis.

Kostarelos K, Teknetzis A, Lefaki I, Ioannides D, Minas A Research and Development Section, Farmeco Co., Athens, Greece.

J Eur Acad Dermatol Venereol 2000 Jan;14(1):5-9

OBJECTIVE: A double-blind, single-site, split-face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17-valerate) scalp application against conditions of psoriasis.

BACKGROUND: Alpha-hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side-effects most frequently associated with use of the latter.

METHODS: Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double-blind, split-face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four-grade scale, prior to treatment and after 2, 4, 6 and 8 weeks.

RESULTS: Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment.

CONCLUSIONS: The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.

Effect of vitamin A on wound epidermis during forelimb regeneration in adult newts.

Koussoulakos S, Sharma KK, Anton HJ. Zoological Institute, University of Cologne, Germany.

Int J Dev Biol. 1990 Dec;34(4):433-9.

The effects of vitamin A on blastemal epidermis were studied during the early postamputational period of forelimb regeneration in Triturus alpestris. Vitamin A was administered through oral intubation at a dose of 250 IU per gram of body weight per day. The results were evaluated by morphometry, histology, and autoradiography. After 7, 11 and 14 days of treatment, several alterations were observed in the wound epidermis: a) reversal of keratinization; fewer keratinized cells were counted in sections from vitamin A-treated limbs; b) decrease in the incorporation of tritiated thymidine, as judged by estimation of labeling indices; c) increased mitotic activity in the cells of the stratum germinativum, and in the middle layer of the epithelial cells, as well. The significance of these cellular effects is discussed against the relevant literature.

[Use of photoprotective measures in relation to actual exposure to solar rays] [Article in Serbo-Croatian (Roman)]

Kozarev J.

Med Pregl. 1998 Nov-Dec;51(11-12):555-8.

OBJECTIVE: There is evidence that in spite of worldwide campaigns against excessive sun exposure, children as well as adults still spend long periods in the sun. The purpose of this study was to evaluate sun exposure in a group of doctors of different specialties and to compare their knowledge about sun protection methods with regular use of sun protection products.

METHODS: 51 doctors of different specialties, volunteers, mean age 40.78, filled out questionnaires with 21 multiple choice questions about their skin type, sun exposure habits, sun protection habits and questions about meaning of the Sun Protection Factor.

RESULTS: Thirty-three percent of our study participants spent more than two peak ultraviolet hours outdoors every day, and additional 33.33% are sun exposed for longer than 5 hours, regularly. Only 39% of them utilized sunscreens. Majority of sunscreen users utilized less than 100 ml of commercial sunscreen products which is an inadequate amount for full body protection per year. Majority of study participants did not believe that sunscreens could prevent skin cancer, but 57% of them believed that these compounds can slow the process of skin aging. Meaning of the term Sun Protection Factor is not familiar to 84.3% study participants. The two most common reasons for not using sunscreens are time consuming application and high cost.

CONCLUSION: Results of the presented study confirm our statement that there is bad understanding of a need for sun protection which is in correlation with deficient application of sun protective measures. It should be stressed out that our study participants lack well formed sun protection habits.

Intracrinology and the skin.

Labrie F, Luu-The V, Labrie C, Pelletier G, El-Alfy M. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), Quebec City, Canada. fernand.labrie@crchul.ulaval.ca

Horm Res 2000;54(5-6):218-29

The skin, the largest organ in the human body, is composed of a series of androgen-sensitive components that all express the steroidogenic enzymes required to transform dehydroepiandrosterone (DHEA) into dihydrotestosterone (DHT). In fact, in post-menopausal women, all sex steroids made in the skin are from adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid by the adrenals decreases progressively from the age of 30 years to less than 50% of its maximal value at the age of 60 years. DHEA applied topically or by the oral route stimulates sebaceous gland activity, the changes observed being completely blocked in the rat by a pure antiandrogen while a pure antiestrogen has no significant effect, thus indicating a predominant or almost exclusive androgenic effect. In human skin, the enzyme that transforms DHEA into androstenedione is type 1 3beta-hydroxysteroid dehydrogenase (type 1 3beta-HSD) as revealed by RNase protection and immunocytochemistry. The conversion of androstenedione into testosterone is then catalyzed in the human skin by type 5 17beta-HSD. All the epidermal cells and cells of the sebaceous glands are labelled by type 5 17beta-HSD. This enzyme is also present at a high level in the hair follicles. Type 1 is the 5alpha-reductase isoform responsible in human skin for the conversion of testosterone into DHT. In the vagina, on the other hand, DHEA exerts mainly an estrogenic effect, this effect having been demonstrated in the rat as well as in post-menopausal women. On the other hand, in experimental animals as well as in post-menopausal women, DHEA, at physiological doses, does not affect the endometrial epithelium, thus indicating the absence of DHEA-converting enzymes in this tissue, and avoiding the need for progestins when DHEA is used as hormone replacement therapy. Copyright 2001 S. Karger AG, Basel

Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin papillomas and carcinomas by dehydroepiandrosterone and 3-beta-methylandrost-5-en-17-one in mice.

Pashko LL, Hard GC, Rovito RJ, Williams JR, Sobel EL, Schwartz AG.

Cancer Res 1985 Jan;45(1):164-6

Topical application of the adrenal steroid, dehydroepiandrosterone, or the synthetic steroid, 3-beta-methylandrost-5-en-17-one, which unlike dehydroepiandrosterone is not demonstrably uterotrophic, inhibits 7,12-dimethylbenz(a)anthracene-induced skin papillomas and carcinomas in the CD-1 mouse.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor formation in mice by 16 alpha-fluoro-5-androsten-17-one and its reversal by deoxyribonucleosides.

Pashko LL, Lewbart ML, Schwartz AG. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.

Carcinogenesis 1991 Nov;12(11):2189-92

The work of ourselves and others has demonstrated that dehydroepiandrosterone (DHEA) dispalys a broad spectrum of cancer preventive action in laboratory rodents, with little toxicity. In the two-stage skin tumorigenesis model in mice, topical application of the synthetic DHEA analog 16 alpha-fluoro-5-androsten-17-one, a more potent preventive agent than DHEA without the sex-hormonal side-effects of the parent steroid, markedly inhibited promotion of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumor development by 12-O-tetradecanoylphorbol-13-acetate (TPA). DHEA is a powerful inhibitor of glucose-6-phosphate dehydrogenase (G6PDH), suggesting that its inhibiting effect in carcinogenesis may be due to a lack of NADPH and ribose-5-phosphate production for deoxyribonucleotide synthesis and subsequent DNA replication. Further evidence of a reduced NADPH and ribose-5-phosphate pool on the lowering of intracellular deoxyribonucleotide levels has been demonstrated in this paper by completely reversing the 16 alpha-fluoro-5-androsten-17-one-induced inhibition of tumor promotion by the addition of the four deoxyribonucleosides-deoxyadenosine, deoxycytidine, deoxyguanosine and thymidine--to the drinking water during the promotion period of tumorigenesis.

Low molecular weight antioxidants and their role in skin ageing.

Podda M, Grundmann-Kollmann M. Department of Dermatology, J. W. Goethe University, Frankfurt, Germany. podda@em.uni-frankfurt.de

Clin Exp Dermatol 2001 Oct;26(7):578-82

There is increasing evidence that reactive oxygen species play a pivotal role in the process of ageing. The skin, as the outermost barrier of the body, is exposed to various exogenous sources of oxidative stress, in particular UV-irradiation. These are believed to be responsible for the extrinsic type of skin ageing, termed photo-ageing. It therefore seems reasonable to try to increase levels of protective low molecular weight antioxidants through a diet rich in fruits and vegetables or by direct topical application. Indeed, various in vitro and animal studies have proved that low molecular weight antioxidants, especially vitamins C and E, ascorbate and tocopherol, as well as lipoic acid, exert protective effects against oxidative stress. However, controlled long-term studies on the efficacy of low molecular weight antioxidants in the prevention or treatment of skin ageing in humans are still lacking.

Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies.

Nyirady J, Bergfeld W, Ellis C, Levine N, Savin R, Shavin J, Voorhees JJ, Weiss J, Grossman R. Johnson & Johnson Consumer Products Worldwide, Skillman, New Jersey 08558-9418, USA.

Cutis 2001 Aug;68(2):135-42

In extensive clinical studies and practical use since its US Food and Drug Administration approval in 1995, tretinoin emollient cream 0.05% has been shown to be safe and effective in the treatment of fine facial wrinkles, mottled hyperpigmentation, and skin roughness. To provide additional prescribing flexibility for various patient needs, a new lower concentration formulation, tretinoin cream 0.02% was chosen for further development. Two multicenter, randomized, double-blind, vehicle-controlled clinical., studies were conducted to evaluate the safety and efficacy of the lower concentration tretinoin formulation in the treatment of moderate-to-severe facial photodamage. Results indicate statistically significant improvement in fine wrinkling, coarse wrinkling, and yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and demonstrated a favorable safety profile. Both studies demonstrated that tretinoin cream 0.02% is safe and effective for the treatment of moderate-to-severe photodamaged facial skin.

The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment.

Ridge BD, Batt MD, Palmer HE, Jarrett A. Beecham Products Research Department, Weybridge, Surrey, U.K.

Br J Dermatol. 1988 Feb;118(2):167-74.

Using a hypomitotic agent, triamcinolone acetonide, and a hypermitotic agent, retinyl propionate, we investigated the relationship between epidermal mitotic activity and stratum corneum renewal time of topically treated skin as determined by the dansyl chloride staining technique. Treatment with the base cream resulted in a reduction in renewal time compared with an untreated control site. The predicted increase in renewal time with the hypomitotic agent and reduction with the hypermitotic agent was only observed when daily treatment was commenced 2 weeks prior to and continued after dansyl chloride staining and not when treatment was started after staining. These results indicate that in order to use cell renewal methods to demonstrate changes in mitotic activity brought about by topical treatments, it is necessary to pre-treat the skin with the test material to establish full epidermal equilibrium at the changed mitotic state before labelling with dansyl chloride. Meaningful claims for effects on cell renewal of specific cosmetic ingredients should only be made after comparison with a base cream treated site, both having been allowed to equilibrate, rather than on the basis of comparison with untreated skin.

Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract.

Saliou C, Rimbach G, Moini H, McLaughlin L, Hosseini S, Lee J, Watson RR, Packer L. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

Free Radic Biol Med. 2001 Jan 15;30(2):154-60.

The procyanidin-rich French maritime pine bark extract Pycnogenol (PBE) has been investigated for its effect in protecting human skin against solar UV-simulated light-induced erythema. Twenty-one volunteers were given an oral supplementation of Pycnogenol: 1.10 mg/kg body weight (b. wt.)/d for the first 4 weeks and 1.66 mg/kg b. wt./d for the next 4 weeks. The minimal erythema dose (MED) was measured twice before supplementation (baseline MED), once after the first 4 weeks of supplementation, and a last time at the end of the study. The UVR dose necessary to achieve 1 MED was significantly increased during PBE supplementation. Since the activation of the pro-inflammatory and redox-regulated transcription factor NF-kappaB is thought to play a major role in UVR-induced erythema, the effect of PBE was also investigated in the human keratinocyte cell line HaCaT. PBE, added to the cell culture medium, inhibited UVR-induced NF-kappaB-dependent gene expression in a concentration-dependent manner. However, NF-kappaB-DNA-binding activity was not prevented, suggesting that PBE affects the transactivation capacity of NF-kappaB. These data indicate that oral supplementation of PBE reduces erythema in the skin. Inhibition of NF-kappaB-dependent gene expression by PBE possibly contributes to the observed increase in MED.

Photoaging of the skin from phenotype to mechanisms.

Scharffetter-Kochanek K, Brenneisen P, Wenk J, Herrmann G, Ma W, Kuhr L, Meewes C, Wlaschek M. Department of Dermatology, University of Cologne, Joseph-Stelzmann-Str. 9, 50931, Cologne, Germany. Karin.Scharffetter@uni-koeln.de

Exp Gerontol. 2000 May;35(3):307-16.

The skin is increasingly exposed to ambient UV-irradiation thus increasing its risk for photooxidative damage with longterm detrimental effects like photoaging, which is characterized by wrinkles, loss of skin tone, and resilience. Photoaged skin displays prominent alterations in the cellular component and the extracellular matrix of the connective tissue with an accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) that deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence, and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS induced photoaging.

Food restriction inhibits [3H] 7,12-dimethylbenz(a)anthracene binding to mouse skin DNA and tetradecanoylphorbol-13-acetate stimulation of epidermal [3H] thymidine incorporation.

Schwartz AG, Pashko LL.

Anticancer Res 1986 Nov-Dec;6(6):1279-82

It has been known for many years that reducing the food intake of laboratory mice and rats inhibits the development of a broad spectrum of chemically induced and spontaneous tumors, but the mechanism of this effect is poorly understood. Food restriction of A/J mice for two weeks is now shown to inhibit the binding of topically applied [3H]7,12-dimethylbenz(a)anthracene (DMBA) to skin DNA by 50% and to abolish the stimulation of [3H]-thymidine incorporation in the epidermis produced by topical application of the tumor promoter tetradecanoylphorbol-13-acetate (TPA). Similar effects on the actions of DMBA and TPA are observed following topical application of the adrenal steroid, dehydroepiandrosterone (DHEA), a potent glucose-6-phosphate dehydrogenase (G6PDH) inhibitor, while food restriction for two weeks depresses epidermal G6PDH activity by 60%. It is suggested that both the inhibition of [3H]DMBA binding to skin DNA and the TPA stimulation in epidermal [3H]thymidine incorporation result from a reduction in the NADPH cellular pool as a result of G6PDH inhibition.

Inhibition of tumor development by dehydroepiandrosterone and related steroids.

Schwartz AG, Pashko L, Whitcomb JM.

Toxicol Pathol 1986;14(3):357-62

The naturally occurring adrenal steroid, dehydroepiandrosterone (DHEA), is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Oral administration of DHEA to mice inhibits spontaneous breast cancer and chemically induced tumors of the lung and colon. Topical application of DHEA to mouse skin inhibits 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and DMBA-induced carcinomas at both the initiation and promotion phase. Evidence is presented that critical steps in the initiation process (mixed-function oxidase activation of a carcinogen) and promotion process (enhanced rates of cell proliferation and superoxide formation) all require NADPH and may be inhibited by DHEA and structural analogs as a result of a lowering of the NADPH cellular pool. Results obtained by others with fibroblasts and lymphocytes from individuals with the Mediterranean variant of G6PDH deficiency also indicate that a reduction in the NADPH cellular pool confers resistance to benzo(a)pyrene. Preliminary data suggest that food restriction may depress G6PDH levels and this may contribute to the tumor preventive effect of underfeeding.

Hypothalamic neuroendocrine correlates of cutaneous burn injury in the rat: I. Scanning electron microscopy.

Scott DE, Vaughan GM, Pruitt BA Jr.

Brain Res Bull. 1986 Sep;17(3):367-78

Rats were given a standard scald burn on 60% of the body surface or only a sham burn and were sacrificed at intervals from 6 hr to 14 days later. Serum thyroxine (T4), free thyroxine index (FT4I) and triiodothyronine (T3) were depressed compared to values in respective shams as early as 6 hr post-burn. T4 and FT4I were less depressed on post-burn days (PBD) 2-3 than on PBD 1 and then exhibited a further fall. T3 remained depressed through PBD 14. Pineal melatonin content was elevated at 6 hr and fell to the normal daytime range in subsequent samples. The ventral portion of the diencephalon was prepared for scanning electron microscopy. Only in the burned rats and beginning on PBD 2, large numbers of supraependymal neurons (SEN) appeared in the ventricular space attached to the inferior walls and floor of the third cerebral ventricle. Transmission electron microscopy was used to confirm the neuronal nature of the SEN. Viewed by scanning electron microscopy, these persisted through PBD 14. SEN were interconnected by cables of their neurites exhibiting varicosities on individual neurites as they passed over perikarya of other SEN. Some SEN were seen to be only partially emerged from the underlying tissue and others were seen to send a thick process into the hypothalamic tissue. These observations indicate that after peripheral injury there is marked plasticity of the brain in an area thought to control the endocrine systems that show abnormalities after such a peripheral injury. The timing, location and nature of these anatomic changes indicate the possibility that at least some aspects of central nervous orchestration of the endocrine metabolic response to injury may be related to the emergence of a neuronal system receiving or sending messages through the cerebrospinal fluid and/or through new neurite circuits along the surface of the third ventricular wall. These structures may appear in response to initial primary hormonal changes and/or may play a role in maintaining the post-injury hormonal milieu manifested in part by a subsequent second fall in serum T4.

Estrogen and skin. An overview.

Shah MG, Maibach HI. University of California, San Francisco, School of Medicine, San Francisco, California, USA. mgshah@alumni.stanford.org

Am J Clin Dermatol 2001;2(3):143-50

As the population of postmenopausal women increases, interest in the effects of estrogen grows. The influence of estrogen on several body systems has been well-documented; however, one area that has not been explored is the effects of estrogen on skin. Estrogen appears to aid in the prevention of skin aging in several ways. This reproductive hormone prevents a decrease in skin collagen in postmenopausal women; topical and systemic estrogen therapy can increase the skin collagen content and therefore maintain skin thickness. In addition, estrogen maintains skin moisture by increasing acid mucopolysaccharides and hyaluronic acid in the skin and possibly maintaining stratum corneum barrier function. Sebum levels are higher in postmenopausal women receiving hormone replacement therapy. Skin wrinkling also may benefit from estrogen as a result of the effects of the hormone on the elastic fibers and collagen. Outside of its influence on skin aging, it has been suggested that estrogen increases cutaneous wound healing by regulating the levels of a cytokine. In fact, topical estrogen has been found to accelerate and improve wound healing in elderly men and women. The role of estrogen in scarring is unclear but recent studies indicate that the lack of estrogen or the addition of tamoxifen may improve the quality of scarring. Unlike skin aging, the role of endogenous and exogenous estrogen in melanoma has not been well established.

Cutaneous vitamins A and E in the context of ultraviolet- or chemically-induced oxidative stress.

Sorg O, Tran C, Saurat JH. Department of Dermatology, University Hospital, Geneva, Switzerland. olivier.sorg@hcuge.ch

Skin Pharmacol Appl Skin Physiol 2001 Nov-Dec;14(6):363-72

Vitamins A and E are present in mammalian skin. Although the main circulating form of vitamin A in the blood is retinol, the epidermis stores it as retinyl esters. The epidermis can be easily loaded with high amounts of vitamin A by topical application of either retinol or retinaldehyde, two well-tolerated precursors of the biologically active retinoic acid, while topical alpha-tocopherol loads the epidermis with vitamin E. The probable physiological function of epidermal vitamin E is to contribute to the antioxidant defense of the skin, whereas that of epidermal vitamin A (retinol and retinyl esters) is not yet well understood. Besides being a precursor for retinoic acid, vitamin A also has a free radical scavenging potential. Due to their physical properties, vitamins A and E absorb ultraviolet (UV) light in the region of solar spectrum that is responsible for most of the deleterious biological effects of the sun. In the mouse, topical vitamin A has been shown to prevent the UV-induced epidermal hypovitaminosis A, while topical vitamin E prevents oxidative stress and cutaneous and systemic immunosuppression elicited by UV. Thus constitutive epidermal vitamins A and E appear complementary in preventing UV-induced deleterious cutaneous and systemic effects, and these properties can be reinforced by topical application of retinol or retinaldehyde and topical alpha-tocopherol. Copyright 2001 S. Karger AG, Basel

Vitamin D insufficiency among free-living healthy young adults

Tangpricha, V., Pearce, E.N., Chen, T.C., Holick, M.F.

Am. J. Med. 2002 Jun 1; 112(8): 659-62.

No abstract available.

Evidence by in vivo and in vitro studies that binding of pycnogenols to elastin affects its rate of degradation by elastases.

Tixier JM, Godeau G, Robert AM, Hornebeck W

Biochem Pharmacol 1984 Dec 15;33(24):3933-9

Procyanidol oligomers and (+) catechin bound to insoluble elastin markedly affect its rate of degradation by elastases. Insoluble elastin pretreated with procyanidol oligomers (PCO) was resistant to the hydrolysis induced by both porcine pancreatic and human leukocyte elastases. The quantitative adsorption of pancreatic elastase was similar on either untreated or PCO-treated elastin suggesting that the binding of this compound to elastin increases the non-productive catalytic sites of elastase molecules. (+) Catechin-insoluble elastin complexes were partially resistant to the degradation induced by human leukocyte elastase but were hydrolysed at the same rate as untreated samples by a constant amount of pancreatic elastase. In addition, the coacervation profile of kappa-elastin peptides as a function of temperature is greatly modified in presence of these flavonoids. We conclusively evidenced that PCOs bind to skin elastic fibres when injected intradermally into young rabbits. As a result, these elastic fibres were found more resistant to the hydrolytic action of porcine pancreatic elastase when injected to the same site. These in vivo studies further emphasized the potential effect of these compounds in preventing elastin degradation by elastase(s) as occurred in inflammatory processes.

Use of topical ascorbic acid and its effects on photodamaged skin topography.

Traikovich SS. Beeson Aesthetic Surgery Institute, Carmel, Ind., USA. AJLively@POL.NET

Arch Otolaryngol Head Neck Surg. 1999 Oct;125(10):1091-8.

OBJECTIVE: To determine the efficacy of topical ascorbic acid application in treating mild to moderate photodamage of facial skin using an objective, computer-assisted image analysis of skin surface topography and subjective clinical, photographic, and patient self-appraisal questionnaires.

DESIGN: A 3-month, randomized, double-blind, vehicle-controlled study.

SETTING: Facial plastic surgery private practice.

PATIENTS: Nineteen evaluable volunteer sample patients aged between 36 and 72 years with Fitzpatrick skin types I, II, and III who were in good physical and mental health with mild to moderately photodamaged facial skin were considered for analysis.

INTERVENTION: Coded, unmarked medications were randomly assigned to the left and right sides of each subject's face, one containing the active agent, topical ascorbic acid (Cellex-C high-potency serum; Cellex-C International, Toronto, Ontario), the other, the vehicle serum (Cellex-C International). Three drops (0.5 mL) of each formulation were applied daily to the randomly assigned hemifaces over the 3-month study period. Treatment assignments were not disclosed to subjects, clinicians, or personnel involved in analyzing skin replicas.

MAIN OUTCOME MEASURES: Specific clinical parameters were evaluated and graded on a 0- to 9-point scale (0, none; 1-3, mild; 4-6, moderate; and 7-9, severe). Reference photographs were used to standardize grading criteria. Overall investigator scores were compared with baseline and graded as excellent (much improved), good (improved), fair (slightly improved), no change, or worse. Patient self-appraisal questionnaires rated the degree of improvement (much improved, improved, slightly improved, no change, or worse) and reported adverse effects (burning, stinging, redness, peeling, dryness, discoloration, itching, and rash). Standard photographs were taken at baseline, including anteroposterior and left and right oblique views to facilitate subsequent clinical evaluations, and at the end of therapy for comparison. Optical profilometry analysis was performed on the skin surface replicas of the lateral canthal (crow's feet) region, comparing baseline to end-of-study specimens. Using this computer-based system, the resulting image was digitally analyzed, and numeric values were assigned to reflect surface features. The parameters obtained included Rz, Ra, and shadows. These values provided objective data that document pretreatment and posttreatment texture changes proportional to the degree of wrinkling, roughness, and other surface irregularities.

RESULTS: Optical profilometry image analysis demonstrated a statistically significant 73.7% improvement in the Ra and shadows north-south facial axis values with active treatment greater than vehicle control, as well as a trend for improvement in the Rz north-south facial axis parameter, showing a 68.4% greater improvement of active treatment vs vehicle control. Clinical assessment demonstrated significant improvement with active treatment greater than control for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, sallowness/yellowing, and overall features. Patient questionnaire results demonstrated statistically significant improvement overall, active treatment 84.2% greater than control. Photographic assessment demonstrated significant improvement, active treatment 57.9% greater than control.

CONCLUSIONS: A 3-month daily regimen of topical ascorbic acid provided objective and subjective improvement in photodamaged facial skin. Skin replica optical profilometry is an objective method for quantification of the skin surface texture changes.

Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2.

Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Department of Laboratory Medicine, University of Toronto, and The Wellesley Hospital, Canada.

Am J Clin Nutr. 1998 Oct;68(4):854-8.

In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. To test the presumption of equivalence in humans, we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [25(OH)D], the measure of vitamin D nutrition. Subjects took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment. With vitamin D2, the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after. The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L, or 1.7 times the increase obtained with vitamin D2 (13.7+/-11.4 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D: 30.6 and 25.5 nmol/L, respectively, for the first and second tertiles. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel.

Uhoda I, Faska N, Robert C, Cauwenbergh G, Pierard GE. Unit of Dermocosmetology, Department of Dermatopathology, University Medical Center of Liege, CHU Sart Tilman, B-4000 Liege, Belgium.

Skin Res Technol. 2002 Aug;8(3):164-7.

BACKGROUND/AIMS: Beyond subjective assessments, the effect of skin tensors is difficult to assess. The present 2-phase randomized double-blind split face study was designed to compare the effect of a gel containing 3% 2-dimethylaminoethanol (deanol, DMAE) with the same formulation without DMAE.

METHODS: In a first pilot study, sensorial assessments and measures of the skin distension under suction were performed in eight volunteers. In a second study conducted in 30 volunteers, shear wave propagation was measured.

RESULTS: Large interindividual variations precluded any significant finding in the first study. The DMAE formulation showed, however, a significant effect characterized by increased shear wave velocity in the direction where the mechanical anisotropy of skin showed looseness.

CONCLUSION: The DMAE formulation under investigation increased skin firmness.

Molecular mechanisms of intrinsic skin aging and retinoid-induced repair and reversal.

Varani J, Fisher GJ, Kang S, Voorhees JJ. Department of Pathology, The University of Michigan, Ann Arbor 48109, USA.

J Investig Dermatol Symp Proc. 1998 Aug;3(1):57-60.

Past studies have shown that topical treatment of sun-exposed skin with all-trans retinoic acid improves the clinical and histologic appearance of the skin. This is associated with a reduction in matrix metalloproteinase elaboration and with expression of a newly synthesized collagenous matrix. Whether retinoid therapy might have a similar impact on the appearance of intrinsically aged skin is not known. This study, using human skin in organ culture and epidermal keratinocytes and fibroblasts in monolayer culture, show that retinoic acid stimulates growth of both keratinocytes and fibroblasts and stimulates extracellular matrix production by the fibroblasts. Adult skin from sun-exposed and sun-protected sites responds equally well to retinoic acid, whereas neonatal skin is much less responsive under the same conditions. The implications of this are (i) that retinoids may be able to repair intrinsically aged skin as well as photoaged skin, and (ii) that retinoids modulate human skin cell function in a manner that is age-related, and not simply a response to photodamage.

Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin.

Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S, Chung JH, Wang ZQ, Datta SC, Fisher GJ, Voorhees JJ. Departments of Pathology and Dermatology, The University of Michigan, Medical School, Ann Arbor, MI 48109, USA. varani@umich.edu

J Invest Dermatol. 2000 Mar;114(3):480-6.

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.

Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it.

Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Mount Sinai Hospital, Toronto, Canada. rvieth@mtsinai.on.ca

Eur J Clin Nutr. 2001 Dec;55(12):1091-7.

OBJECTIVE: We asked whether women self-reporting the recommended consumption of vitamin D from milk and multivitamins would be less likely to have low wintertime 25-hydroxyvitamin D (25(OH)D) levels.

METHODS: This cross-sectional study enlisted at least 42 young women each month (age 18-35 y, 796 women total) through one year. We measured serum 25(OH)D and administered a lifestyle and diet questionnaire. RESULTS: Over the whole year, prevalence of low 25(OH)D (<40 nmol/l) was higher in non-white, non-black subjects (25.6% of 82 women) than in the white women (14.8% of 702 white women, P<0.05). Of the 435 women tested during the winter half of the year (November-April), prevalence of low 25(OH)D was not affected by vitamin D intake: low 25(OH)D occurred in 21% of the 146 consuming no vitamin D, in 26% of the 140 reporting some vitamin D intake, up to 5 microg/day (median, 2.5 microg/day), and in 20% of the 149 women reporting vitamin D consumption over 5 microg/day (median, 10 microg/day).

INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. Vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration.

Synthesis and characterization of a series of novel monoacylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids, as skin antioxidants.

Yamamoto I, Tai A, Fujinami Y, Sasaki K, Okazaki S. Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. iyamamoto@pheasant.pharm.okayama-u.ac.jp

J Med Chem 2002 Jan 17;45(2):462-8

A series of novel monoacylated vitamin C derivatives were chemically synthesized with a stable ascorbate derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and acid anhydrides in pyridine. Their solubility in organic phase, thermal stability, radical scavenging activity, and in vitro skin permeability was evaluated. These monoacylated derivatives were identified as 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G) by UV spectra, elemental analyses, and nuclear magnetic resonance spectroscopy. The reactions afforded 6-Acyl-AA-2G in high yields (30-60%). 6-Acyl-AA-2G exhibited satisfactory stability in neutral solution comparable to that of a typical stable derivative, AA-2G, and also showed the radical scavenging activity. The lipid solubility of 6-Acyl-AA-2G was increased with increasing length of their acyl group. Increased skin permeability was superior to those of AA-2G and ascorbic acid (AsA). 6-Acyl-AA-2G that is susceptible to enzymatic hydrolysis by tissue esterase and/or alpha-glucosidase produces AA-2G and AsA, which is in the skin tissues. Thus, these findings indicate that the novel vitamin C derivatives presented here, 6-Acyl-AA-2G, may be effective antioxidants in skin care and medicinal use.

Pion IA; Kopf AW; Hughes BR; Wetton NM; Collins M; Newton Bishop JA
Ronald O. Perelman Department of Dermatology, New York University (NYU) School of Medicine, New York, New York, USA.
Pediatr Dermatol (United States) Jan-Feb 1997, 14 (1) p6-12

Childhood exposure to sunlight is a risk factor for melanoma . To formulate a meaningful program to educate children about the ill effects of the sun, their extant knowledge base must be determined. We have used the "draw-and-write" technique to assess children's perceptions about the sun, suntans, and skin cancer. A total of 693 school children aged 4 to 13 years were asked to draw pictures and label them in response to a series of carefully worded questions. Awareness of the need to apply sunscreen increased from 44% in children aged 4 to 6 years to 95% in children aged 9 to 10 years. Ten percent of children aged 4 to 6 years already perceived a suntan as attractive. While almost all children were aware of the negative immediate effects of sun exposure, namely sunburn, just 30% of American children aged 11 to 13 were aware that sun exposure is a risk for skin cancer. No differences between boys and girls were seen. The "draw-and-write" technique allows assessment of the attitudes and perceptions of children regarding the sun and skin cancer. It also provides valuable information on which to base health education and evaluate its cost-effectiveness.

Castillero Pinilla C.; Saldivar Moreno C.; Lopez Graniel C.
Dr. C. Castillero Pinilla, Instituto Nacional de Cancerologia, Division de Ensenanza, Av. San Fernando num. 22, Col. Tlalpan, 14000 Mexico D.F. Mexico
Revista del Instituto Nacional de Cancerologia (Mexico) 1998, 44/4 (205-209)

Malignant melanoma is currently the tumor with the most accelerated incidence increase. The incidence of malignant melanoma of the trunk is increasing in well-developed countries and represents the third most common location, just after head and neck and limbs. Risk factors associated with this location are hereditary syndromes and sun-burns during childhood and adolescence; however, there is a strong association with preexisting nevuses. The prevention of malignant melanoma of the trunk is the same than for other site malignant melanomas, being necessary the use of sunblockers during childhood and adolescence. Treatment is directed toward the use of vital blue dye sentinel-node mapping for managing regional nodes, with preoperative lymphoscintigraphy. Primary tumor must be managed according to established surgical margins for any other malignant melanomas, 1 cm for less than 1 mm- depth lesions, 2 cm for more than 1.1 mm-depth lesions. Prognosis is determined mainly by the clinical stage.

Carter R.; Marks R.; Hill D.
R. Carter, Health Economics Unit, Centre for Health Program Evaluation, PO Box 477, West Heidelberg, Vic. 3081 Australia
Health Promotion International (United Kingdom) 1999, 14/1 (73-82)

This study aimed to determine the potential cost-effectiveness of initiating a co-ordinated and comprehensive national skin cancer primary prevention campaign in Australia. The study is undertaken from the perspective of the Federal government as potential funder of a national initiative, but other perspectives are analysed. Using the SunSmart Campaign in the Stat of Victoria, Australia, as a model for the national program, estimates were made of the reduction in the incidence and associated premature mortality for skin cancer that would accompany reduction in sunlight exposure. Cost offsets to government flowing from the reduction in management costs for skin cancer were estimated and deducted from the cost of the health promotion campaign. Costs affecting individuals, such as the cost of sunscreen, were included in the sensitivity analysis. On the basis of the asumptions used (with a 'do nothing' comparator), a national campaign involving a 20-year commitment of $AUD 5 million annually (i.e. 28c per person) would avoid 4300 premature deaths and cost $AUD 1360 per life-year saved, or $AUD 14,360 per death deferred. If the cost offsets are included, the program should not only prevent premature deaths but also yield a net saving to government of $AUD 103 million (PV). In the sensitivity analysis the results were robust to a variety of cost and outcome variations. Increasing the lag between decreases in UVR exposure and falls in the incidence of melanoma from 5 to 15 years, and inclusion of costs affecting individuals and their families had the largest effects on cost-effectiveness. The cost per life-year saved (excluding cost effects) increased from $AUD 1360 to $AUD 5103 and $AUD 25,134 respectively. A survey of current expenditure by State/Territory government departments and anticancer bodies on skin cancer primary prevention was carried out as part of the analysis and an annual commitment of $AUD 5 million by the Federal government represents a doubling of current expenditures (of approximately 14c per person). The cost-effectiveness (using a 'current practice' comparator) yields a cost of $AUD 2715 per life-year saved (ignoring the cost offsets and using a conservative estimate of improved health outcomes attributed to the new national program). The study results, although indicative only, strongly suggest that a comprehensive national skin cancer primary prevention program would be excellent 'value for money' from a variety of perspectives, using both 'do nothing' and 'current practice' comparators.

Hochman M.; Lang P.
Dr. P. Lang, Department of Dermatology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States
Medical Clinics of North America (United States) 1999, 83/1 (261-282)

The incidence of skin cancers is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious skin lesion may first present to their primary care physician for evaluation. Therefore, it is important for the primary care physician to be able to distinguish between benign and malignant pigmented lesions, to know how to evaluate such a patient, and to appreciate the importance of appropriate interdisciplinary management of these patients.

Wille L.; Kolmel K.F.; Gefeller O.
Dr. O. Gefeller, Abteilung Medizinische Statistik, Georg-August-Universitat Gottingen, Humboldt-allee 32, 37073 Gottingen Germany
Zeitschrift fur Dermatologie (Germany) 1998, 184/2 (82-85)

The importance of sunscreens for primary prevention of malignant melanoma is controversial. An overview of all published case-control studies about this topic shows that due to very heterogeneous scientific results neither quantitative nor qualitative statements are possible at the moment whether the use of sunscreens has a protective, a neutral, or an increasing risk effect for the development of melanoma . The responsible factors leading to the observed discrepancies between the studies are discussed in the article. In the current state of knowledge, the necessary reduction of UV- radiation should be preferably ensured by wearing textile sun protection.

Brash D.E.; Ponten J.
D.E. Brash, Department of Therapeutic Radiology, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, CT 06520 United States
Cancer Surveys (United States) 1998, 32/- (69-113)

Squamous cell carcinoma of the skin and melanoma are the rare progeny of precancerous lesions that usually remain stable or regress. For SCC the sequence appears to include TP53 mutant clones in normal skin; dysplasia; carcinoma in situ; and SCC. When such lesions are contiguous, their TP53 mutations are consistent with a single clonal lineage. The set of TP53 mutations in tumours is more restricted than in precancers, suggesting additional selection. Melanoma lies at the end of a continuum including mole, dysplastic naevus, radial growth melanoma and vertical growth. The genetics of melanoma is less clear. Basal cell carcinomas seem to arise without a precancer and contain mutations in TP53 and PTCH. Childhood sunlight exposure directs the location and frequency of precancers. For melanoma, its effects on intermittently exposed body sites are super-imposed on the effect at sites chronically exposed. SCC precancers and tumours, BCC tumours and melanoma cell lines contain UV induced mutations. Sun exposed skin of normal individuals contains thousands of small clones of TP53 mutated cells. Predisposition to sunlight induced precancer is a multigenic trait involving factors such as hair and skin color, DNA repair proficiency and mole type and number. These each contribute a relative risk on the order of two to four. Familial predisposition to dysplastic naevi carries a larger risk. The cell of origin for melanoma is uncontroversial, and the proposed hair follicle origin of BCC is consistent with the presence of stem cells in the bulge region. The origin of SCCs and the arrangement of interfollicular stem cell compartments are less clear. Clonal expansion of the initial mutated cell may also be driven by sunlight. When a mutation confers apoptosis resistance, as TP53 mutations do, subsequent UV exposure will be more likely to kill normal cells than mutants. The latter can expand into a clone, only one cell of which need be mutated again. Immunosuppressant drugs may have the same effect as UV, facilitating the clonal expansion of precancers. In the absence of exogenous influences, mutant clones and precancers tend to regress. There is little evidence that regression of precancers is immunological, though regression of melanoma appears to be. The chemotherapeutic agent 5-FU causes regression of dysplasias by removing initiated cells, perhaps by enhancing apoptosis. In contrast, retinoic acid temporarily suppresses clonal expansion. Most sunscreens are mutagenic, with as yet unknown consequences. Mice develop dysplasias and SCCs after UV irradiation. Initiation and clonal expansion of dysplasias is UV driven, but conversion to SCC and subsequent growth involve spontaneous events. With chemical carcinogens mice develop papillomas that usually regress and thus are precancers. Tumour promotion yields abundant low risk papillomas that contain Hras1 mutations but rarely progress to SCC. High risk papillomas are infrequent but do convert to SCC, particularly if re-treated with mutagens. Conversion to SCC is associated with TP53 mutations. The mechanisms of multiple mutation and clonal expansion observed in human and mouse systems, respectively, are beginning to converge into a coherent understanding of precancerous events in skin.

Tenkate T.D.
T.D. Tenkate, School of Public Health, Dept. of Environmental Health Sci., University of Alabama, 1665 University Blvd., Birmingham, AL 35294-0022 United States
Journal of Environmental Health (United States) 1998, 61/2 (9-15)

This article provides an overview of human exposure to ultraviolet radiation (UVR) and associated health effects, as well as risk estimates for acute and chronic conditions resulting from UVR exposure. For most people, the main source of UVR is the sun. Adverse health effects include photokeratitis, erythema, pterygium, some types of cataracts, basal and squamous cell carcinomas, and malignant melanoma . Human exposure is influenced by the following factors: type of occupation, protective measures employed, types of recreational activities undertaken, and personal behavior. Acute conditions may result within 30 minutes of noontime sun exposure, and the minimum risk estimate for nonmelanoma skin cancer (NMSC) in a person 70 years of age is two to three percent. Risks for NMSC are increased for outdoor workers and those participating in recreational sun exposure, but can be significantly reduced if sunscreen is used during childhood.

Wille L.; Gefeller O.; Kolmel K.F.
Dr. O. Gefeller, Abteilung Medizinische Statistik, Georg-August-Universitat Gottingen, Humboldtallee 32, D-37073 Gottingen Germany
H+G Zeitschrift fur Hautkrankheiten (Germany) 1998, 73/7-8 (467-473)

The use of sunscreens is regarded as protective behaviour against the development of malignant melanoma by the public. A meta-analysis on the importance of the application of sunscreens for primary prevention of malignant melanoma of the skin on the basis of all published case-control studies, however, implies that neither a quantitative nor a qualitative statement concerning the protective or detrimental effect of these agents is possible. This article discusses in detail the discrepancies between the studies leading to this decision. Furthermore, the paper deals with hypotheses for explaining these results. We conclude on the basis of the available epidemiologic studies that public health efforts should not emphasize the use of sunscreens for primary prevention of malignant melanoma . The necessary reduction of UV-radiation should be preferably ensured by staying in the shade and by wearing textile sun protection.

Drug and Therapeutics Bulletin (United Kingdom) 1998, 36/7 (49-51)

In the UK, the incidence of newly diagnosed skin cancer appears to be doubling every 10 years; there were over 40,000 new cases last year. Here we discuss the place of sunscreens in the prevention of skin cancer.

Murphy G.M.
G.M. Murphy, Photobiology Unit, Beaumont Mater Misericordiae Hosp, Dublin Ireland
Journal of Dermatological Treatment (United Kingdom) 1998, 9/Suppl. 2 (17-21)

Although not well understood a relationship exists between sun exposure and malignant melanoma . Sunscreens are important in reducing the damage that ultraviolet (UV) irradiation exposure from sunlight causes to the skin. Overall, the major risk for malignant melanoma seems to lie with excessive UVB exposure with some contribution by UVA. Therefore, reduction of both UVB and UVA exposure is advocated for both sporadic and familial malignant melanoma . If a sunscreen is only partly applied, or only UVA or UVB formulations are used, individuals will have a false impression of the level of protection provided and will expose themselves for prolonged periods increasing their risk of skin damage. Today, there are a number of effective sunscreens available, with relatively equivalent UVA and UVB protection and photostable ingredients. The effectiveness of even the best sunscreen, however, is completely dependent on whether or not it is used properly. It is important that individuals are advised on their behaviour in the sun, and the correct application and choice of sunscreen products.

Tsao H.; Rogers G.S.; Sober A.J.
Dr. A.J. Sober, Department of Dermatology, Massachusetts General Hospital, Bartlett Hall, Blossom St., Boston, MA 02114 United States
Journal of the American Academy of Dermatology (United States) 1998, 38/5 I (669-680)

Background: Although the survival benefits of early stage melanoma have been clearly documented, the potential economic impact of early versus late stage disease has not been assessed.

Objective: Our purpose was to estimate the annual direct cost of diagnosing and treating melanoma, based on the number of projected cases of melanoma entering each stage in 1997.

Methods: A model was constructed with assumptions derived from the literature and clinical experience at the Massachusetts General Hospital Melanoma Center and the Boston University Medical Center. Cost estimates were based on 1997 Boston area Medicare reimbursements.

Results: The annual direct cost of treating newly diagnosed melanoma in 1997 was estimated to be $563 million. Stage I and II disease each comprised about 5% of the total cost; stage III and stage IV disease consumed 34% and 55% of the total cost, respectively. About 90% of the total annual direct cost of treating melanoma in 1997 was attributable to less than 20% of patients (those patients with advanced disease, that is, stage III and stage IV).

Conclusion: In addition to the potential survival advantages, aggressive primary prevention through sun protection and intensive screening to enhance earlier detection should reduce the economic burden of melanoma care.

Gordon M.L.; Hecker M.S.
Dr. M.L. Gordon, Department of Dermatology, Mount Sinai Medical Center, New York, NY United States
Geriatrics (United States) 1997, 52/8 (56-68)

Intrinsic skin changes with advancing years include dryness, decreasing elasticity, increasing skin fragility, and more prominent vasculature. Extrinsic skin aging, caused primarily by cigarette smoking and exposure to sunlight, includes mottled pigmentation and yellow discoloration, rough leathery textural changes, and wrinkling. Major premalignant and malignant neoplasms in photodamaged skin are actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and melanoma . Nonmalignant lesions include solar lentigines and seborrheic keratoses. The A, B, C, D criteria can assist in the evaluation of pigmented nevi. Physicians play an important role in educating patients about the health risks associated with excessive sun exposure and about sun protection to prevent further skin damage.

Bergfeld W.F.
Dr. W.F. Bergfeld, Department of Dermatology, Cleveland Clinic Foundation, Cleveland, OH 44195 United States
International Journal of Fertility and Women's Medicine (United States) 1997, 42/2 (57-66)

In the past, sun exposure has been an integral part of the American life style. Along with increased leisure time, outdoor recreational sports, and sun bathing has come greater exposure to the sun. The cumulative effects of unprotected sun exposure coupled with the changes in the ozone layer have resulted in a large photodamaged population and an epidemic of the most dangerous skin cancer, malignant melanoma . Photodamage begins early, with a child's first unprotected sun exposure. Clinical studies show that 50% of an individual's ultraviolet light exposure occurs before the age of 18 years. This damage from acute and chronic ultraviolet light exposure has produced the explosion of skin cancers. Over the next 4 years, it is expected that skin cancer will become the most common type of cancer, and malignant melanoma will become the leading cause of death from skin cancer. This growing hazard to the public has profound medical and psychological ramifications. This paper will focus on prevention, identification, evaluation and treatment of photodamage to skin, as well as skin cancer. Special emphasis will be given to the National Skin Cancer Prevention Education Program.

Ferrini R.L.; Perlman M.; Hill L.; Devlin M.
M. Devlin, 1660 L. Street, NW, Washington, DC 20036 United States
American Journal of Preventive Medicine (United States) 1998, 14/1 (83-86)

Based on a review of current literature and recommendations, the American College of Preventive Medicine presents a practice policy statement on skin protection from ultraviolet light exposure.

Langley R.G.B.; Sober A.J.
Dr. A.J. Sober, Harvard Medical School, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114 United States
Cancer Investigation (United States) 1997, 15/6 (561-567)

Strong epidemiological evidence exists that solar radiation is causally related to a significant proportion of cutaneous melanoma . The nature of the relationship is, however, complex and the details are not entirely clear. There appears to be a complex interplay between solar exposure in individuals with a characteristic phenotype. Although the exact quantitative and qualitative nature of this exposure is not clear, it is probable that intermittent exposures and intense exposures with consequent sun-burns in a high-risk phenotype are critical in increasing the risk of developing melanoma . Despite the lack of complete understanding of this relationship, the evidence is convincing that solar radiation is causally related to cutaneous melanoma and consequently exposures to UV radiation should be reduced from early in life. The preventive measures involve reducing exposure to ambient solar radiation, by avoiding peak exposures, wearing protective outerwear, and using broad-spectrum sunscreens.

Ley R.D.; Reeve V.E.
Dr. R.D. Ley, The Lovelace Institutes, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 United States
rley@Iri.org
Environmental Health Perspectives (United States) 1997, 105/Suppl. 4 (981-984)

The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunburn. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma . Whereas sunscreens are undoubtedly effective in preventing sunburn, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma . Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice and humans. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis.

Autier P.; Dore J.-F.; Cesarini J.-P.; Boyle P.
J.-F. Dore, INSERM U 453, Centre Leon Berard, 28, rue Laennec, F-69373 Lyon Cedex 08 France
Annals of Oncology (Netherlands) 1997, 8/5 (435-437)

Background: Psoralens are potent tanning activators that have been introduced in France and in Belgium in some tanning lotions and sunscreens. It was shown that poor tanners who ever used psoralen tanning activators display a four-fold increase in melanoma risk when compared to poor tanners using regular sunscreens. Although psoralens have now been banned from suntan lotions, it is likely that the increase in melanoma risk linked to their previous use will persist for several years.

Methods: The melanoma risk attributable to psoralens use was calculated to evaluate the population at risk in France and Belgium.

Results: Melanoma incidence for the year 1995 was estimated to be of 10.2 per 100,000 in France and of 10.0 per 100,000 in Belgium, representing 5,900 and 1,000 melanoma cases. From the melanoma incidence among poor tanner who ever used psoralens (52 per 100,000) and and estimation of the percentage of psoralen users among poor tanners, it can be derived that, for the year 1995, 267 melanoma cases could be attributed to psoralen tanning activators.

Conclusions: Subjects who used psoralen suntan activators should be informed of their increased melanoma risk and be encouraged to participate in clinical programmes for early detection of melanoma, more especially when they are poor tanners and display a high naevi count. Such an action could save a significant number of lives.

English D.R.; Armstrong B.K.; Kricker A.; Fleming C.
Dr. D.R. English, Department of Public Health, University of Western Australia, Perth, WA 6907 Australia
Cancer Causes and Control (United Kingdom) 1997, 8/3 (271-283)

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Keller K.L.; Fenske N.A.; Glass L.F.
Dr. L.F. Glass, Div. of Dermatology/Cutaneous Surg., College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612 United States
Clinics in Geriatric Medicine (United States) 1997, 13/2 (339-361)

This article focuses on the common precancers and skin cancers in the older patient. The hazards of ultraviolet radiation are explained briefly in relation to photoaging and the development of skin cancer. The etiology, clinical appearance, histopathologic diagnosis, treatment, and follow-up for each type of cancer are reviewed thoroughly. It is hoped that early recognition and treatment by geriatric physicians will have a positive impact on the reduction of the morbidity and mortality associated with these cancers in the elderly.

Naylor M.F.
Dr. M.F. Naylor, Oklahoma Ctr. for Molecular Medicine, Univ. of Oklahoma Health Sci. Ctr., 941 Stanton L. Young Blvd, Oklahoma City, OK 73104 United States
Archives of Dermatology (United States) 1997, 133/3 (373-375)

Ultraviolet-induced erythema is now recognized as an important clinical marker for skin cancer risk. People with a history of repeated erythematous exposures to sunlight are more likely to develop both melanoma and nonmelanoma skin cancers. Is erythema the most important thing we need to be concerned about in terms of protecting the public from the harmful effects of sunlight? What do we know about UV-induced erythema, and why is it a powerful influence on skin cancer risk?.

Harvey I; Frankel S; Marks R; Shalom D; Nolan-Farrell M
Department of Social Medicine, University of Bristol, UK.
Br J Cancer (Scotland) Oct 1996, 74 (8) p1308-12

This study aimed to identify risk markers for prevalent solar keratoses (SKs) and squamous cell carcinomata (SCC) combined, for incident SKs and for spontaneous remission of SKs and to evaluate primary preventative measures. It was a cross-sectional study, with follow-up, conducted in South Wales, and involved 1034 subjects aged 60 years and over. The main outcome measures were the presence of and changes in SKs, and presence of skin cancers, on sun-exposed skin, and risk factors for prevalent SKs/SCCs and for incidence and remission of SKs. We found that variables independently associated with prevalent SKs/SCCs were: age [80 + years vs 60-64 years, odds ratio (OR) 3.7]; sex (male vs female OR 2.2); cumulative sun exposure (top quintile vs bottom quintile OR 3.3) and skin type (skin type 1 vs 4 OR 12.4). Use of sunscreen or protective clothing was not protective after controlling for confounders. Males and those who sunbathe infrequently showed greater remission of SKs. Older subjects and those spending most time in the sun in the preceeding 2 years were most likely to develop new SKs. We conclude that the risk factors identified are consistent with results from sunnier countries. The failure of sunscreen or clothing to emerge as protective raises doubts as to whether these measures are as effective in routine use in the general population as theoretical considerations and the limited trial evidence would predict. Recently reported sun exposure appears to influence the risk of developing new SKs.

Reynolds KD; Blaum JM; Jester PM; Weiss H; Soong SJ; Diclemente RJ
Department of Health Behavior, University of Alabama at Birmingham 35294-2010, USA.
J Adolesc Health (United States) Dec 1996, 19 (6) p409-15

PURPOSE: With the increase in melanoma incidence, the sun exposure and protective behaviors of adolescents are of great concern. Limited data are available on the prevalence and predictors of risk behavior in adolescents in the southeastern United States. This study examined the levels of sun exposure and variables predictive of sun exposure among adolescents in two Alabama middle schools.

METHODS: A total of 509 sixth-graders completed a self-administered survey assessing: (a) their knowledge, attitudes, and beliefs about malignant melanoma ; and (b) their sun exposure and sunburns for a specific weekend and for the summer.

RESULTS: Levels of sun exposure and frequency of sunburn were high. Regression models determined the predictors of weekend and summer sun exposure, and weekend sunburn. Significant predictors varied by outcome and included gender, perceived importance of a suntan, parent and peer modeling, and sunscreen use.

CONCLUSION: Reducing the risk of melanoma will require a three-pronged intervention strategy with efforts directed at adolescents, their parents, and the broader community.

Donawho C; Wolf P
University of Texas M.D. Anderson Cancer Center, Department of Immunology, Houston 77030, USA.
Curr Opin Oncol (United States) Mar 1996, 8 (2) p159-66

This paper reviews the current epidemiologic and experimental evidence regarding the effect of sunburns on cutaneous malignant melanoma and the possible effectiveness of sunscreens in preventing those effects. Although there is growing agreement that sunlight exposure, particularly the ultraviolet wavelengths in solar radiation, contributes to the etiology of cutaneous malignant melanoma, there are at present insufficient data on the effective ultraviolet waveband and whether the use of sunscreens may be useful in preventing melanoma . The main obstacle in answering this question is that the exact role of sunlight in the pathogenesis of melanoma still remains undefined. However, new experimental animal models are now available that will assist in determining and defining the mechanism of initiation and promotion of melanoma by sunlight and, particularly, ultraviolet radiation in sunlight. While we await more definitive data, it is reasonable to recommend an overall "safe sun strategy" in which the use of sunscreens certainly must be accompanied by other protective measures of overall reduction of sunlight exposure. (57 Refs.)

Bartak P
Statni zdravotni ustav, Praha.
Cas Lek Cesk (Czech Republic) Jul 26 1996, 135 (13) p403-4

Since the beginning of the 19th century the scientific knowledge concerning the effect of the sun rays upon the human organism, mainly on the skin, has been studied and the components of the sun spectrum were specified. During the last years the ozone layer was seriously damaged due to the so called civilization and the very harmful UVC component of the spectrum has entered the earth atmosphere. The accumulation of the unhealthy human habits and the new sun aggression threaten the human skin. The result is the growing number of the skin cancer, incl. melanoma of young people. The whole world dermatologists common opinion is that only the proper knowledge of this sun danger and the daily behaviour change combined with adequate dress and reliable sunscreen are able to prevent the serious damage in not very distant future.

Farmer KC; Naylor MF
Department of Pharmacy Practice, College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City 73117, USA.
Ann Pharmacother (United States) Jun 1996, 30 (6) p662-73

OBJECTIVE: To review the role of sunlight in skin aging and skin cancer formation, and to provide guidelines on the use of sunscreens to minimize the adverse effects of sun damage.

DATA SOURCES: A MEDLINE search of applicable articles on ultraviolet (UV) radiation, melanoma, sunscreens, and skin cancer, evaluating both human and animal studies. Published and unpublished original research as well as clinical experience were also used.

DATA SYNTHESIS: The interaction of UV radiation and skin type plays a central role in melanoma formation. Mortality from melanoma is highest in geographic locations near the equator, where UV intensity is greatest. The incidence of melanomas in light-complected individuals (skin types I-III) is several times higher than those with darker skin types (types IV-VI), even in similar geographic regions. The UVB portion of the spectrum appears to be primarily responsible for skin cancer formation and photoaging, while short wave UVA rays play a significant contributing role. Regular sunscreen use has been shown to reduce the formation of precancerous actinic keratoses (AK) lesions by 36%. A dose-response relationship has also been found between the amount of sunscreen used and AK formation.

CONCLUSIONS: Sunscreens have now been shown to reduce the carcinogenic effects of sunlight in humans. Patients should be advised of the long-term consequences of sun exposure and the benefits of regular sunscreen use. (87 Refs.)

Kubar WL; Rodrigue JR; Hoffmann RG 3rd
Center for Pediatric Psychology Research, University of Florida Health Science Center, Gainesville 32610-0165, USA.
Psychol Rep (United States) Dec 1995, 77 (3 Pt 2) p1136-8

This study examined the relationships among measures of knowledge of skin cancer, attitudes toward sun exposure, intentions to use sunscreen, and self-reported use of sunscreen by 105 fifth-grade children. Positive correlations were obtained between knowledge and intentions to use sunscreen, knowledge and healthier attitudes, and intentions to use sunscreen and healthier attitudes toward sun exposure. Surprisingly, knowledge, attitudes, and intentions were not significantly associated with reported use of sunscreen . Researchers designing interventions to effect behavioral change, i.e., sunscreen use, in children might further explore the predictive utility of these constructs as well as examine the utility of other important variables not measured here.

Marks R
University of Melbourne, Department of Medicine (Dermatology), St Vincent's Hospital Melbourne, Australia.
J Dermatol (Japan) Nov 1995, 22 (11) p853-7

Non-melanoma skin cancer (NMSC) comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in humans in many countries. Sunlight plays a major part in the development of these tumours which appear predominantly on areas of the most frequently exposed skin. The site distribution for BCC and SCC is not the same, with SCC being most common on the sites of very heavy exposure and BCC becoming more common on areas of only moderate exposure, e.g. upper trunk in men and women and lower leg in women. Incidence rates of NMSC, where they are being recorded, show rises over time. Mortality rates, on the other hand, have been dropping most of this century until they have been levelling out recently. The case fatality rate due to SCC appears to be between 1-2%. The malignant transformation rate of actinic keratoses to SCC appears to be very low. Studies on similar populations at different latitudes allow estimates to be made of increases which might occur with increasing exposure to ultraviolet radiation (UVR) over a life time. These have been used to estimate the possible increases in NMSC due to stratospheric ozone depletion. Finally, recent studies on the reduction of existing actinic keratoses and prevention of new ones with regular use of sunscreen augurs well for prevention of NMSC in the future. (27 Refs.)

Bourke JF; Graham-Brown RA
Department of Dermatology, Leicester Royal Infirmary, U.K.
Br J Dermatol (England) Aug 1995, 133 (2) p264-6

The incidence of melanoma in the U.K. is increasing more rapidly than that of most other malignant tumours. Sunburn in childhood increases the risk of malignant melanoma in later life and it is therefore essential that protection of children is improved if primary prevention of melanoma is to be effective. We asked 238 parents in Leicester how they protected their children against sunburn, how often their children suffered sunburn, and whether they had heard of malignant melanoma . Although most (80%) had heard of melanoma, 47% did not regularly ensure that their children used a sunblock lotion, and only 34% regularly protected them from the midday sun. Forty-eight per cent of parents stated that their children burned at least once a year. New approaches to public education about melanoma may be needed to improve the protection of children against sunburn.

Autier P; Dore JF; Schifflers E; Cesarini JP; Bollaerts A; Koelmel KF; Gefeller O; Liabeuf A; Lejeune F; Lienard D; et al
Int J Cancer (United States) Jun 9 1995, 61 (6) p749-55

Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma . In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% Cl:1.09-2.06) for regular sunscreens, and of 2.28 (95% Cl: 1.28-4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% Cl: 1.25-15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens.

Holly EA; Aston DA; Cress RD; Ahn DK; Kristiansen JJ
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143, USA.
Am J Epidemiol (United States) May 15 1995, 141 (10) p923-33

A population-based case-control study of cutaneous malignant melanoma (CMM) was conducted in 452 women with melanoma and 930 control subjects aged 25-59 years in five San Francisco Bay Area counties between 1981 and 1986. Women were interviewed in their homes with regard to history of sunlight exposure and sunburns during different periods in their lives, phenotypic and host characteristics, medical history, occupation, and demographic factors. Data were analyzed by the patients' histologic type of melanoma ; 355 women were classified as having superficial spreading melanoma (SSM), 61 had nodular melanoma (NM), 13 had lentigo maligna melanoma, and 23 had other melanomas that could not be further classified upon histologic review by University of California dermatopathologists. Univariate results from analysis of factors related to sun exposure showed that the risk of all histologic types of CMM, SSM, and NM increased with increasing tendency of the subject to sunburn and with history of increased severity and/or frequency of sunburns up to age 12 years. Risk of all types of CMM and SSM also increased with increasing number of sunburns for all age groups and with lack of use of sunscreen . After adjustment for each other and for phenotypic factors, history of sunburn up to age 12 and lack of sunscreen use were the primary sun-related factors associated with an increased risk of all types of CMM and SSM, while tendency to sunburn when exposed to 1/2 hour of noontime sun and lack of use of sunscreen were related to NM. Although having frequent sunburns before age 12 and having severe sunburns before age 12 were both strongly associated with melanoma, having large numbers of sunburns during any time period from elementary school through age 30 years and having sunburns during the 10 years prior to diagnosis or interview were all associated with a doubling of risk for SSM after adjustment for other factors. These results suggest that the increased risk of melanoma related to sunburns is not confined to childhood sunburns. Maintenance of an all-year tan provided no protective effect against melanoma after adjustment for tendency to burn. No association was noted with use of fluorescent lights or exposure to sunlamps for all types of CMM, SSM, or NM.

Westerdahl J; Olsson H; Masback A; Ingvar C; Jonsson N
Department of Surgery, University Hospital, Lund, Sweden.
Melanoma Res (England) Feb 1995, 5 (1) p59-65

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma . Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

Jansen C
Kliniska Institutionen, Abo Universitet.
Nord Med (Sweden) 1995, 110 (3) p85-7

Ultraviolet radiation (UVR) exerts a variety of effects on the skin, most of which are inimical. Best known is the effect of UVB radiation which readily burns unprotected skin, but we now know that even UVA radiation may exert penetrating effects on the skin, as well as causing DNA damage and increased risk of cancer. The markedly increased incidence of basal cell and squamous cell carcinoma and malignant melanoma among fair-skinned Caucasians in industrialised countries is attributed to increased exposure to UVR. Sunscreen creams may have exacerbated the situation. Effective phototherapy is a useful product of photomedical research, and it can be further improved. Recently new perspectives were opened up in basic research into UVR, when it was found that repair of DNA lesions via different pathways orchestrates a series of cellular phenomena such as oncogene expression, acid radical defence, immunomodulation, apoptosis and pigmentation induction. (12 Refs.)

Bourke JF; Healsmith MF; Graham-Brown RA
Department of Dermatology, Leicester Royal Infirmary, U.K.
Br J Dermatol (England) Feb 1995, 132 (2) p251-6

The city of Leicester, in conjunction with other centres throughout the U.K., was targeted for publicity about melanoma over a 3-year period from 1987 to 1989. We report the results of a survey to assess the level of awareness of melanoma, and to document current sunbathing practices subsequent to that period. The general level of awareness of melanoma in the community was good (74%). People who knew about melanoma were more likely to use a sunscreen at home and abroad (odds ratios 1.63, 95% CI 1.19-2.24 and 1.39, 95% CI 1.03-1.86), but paradoxically more likely to sunbathe than those who had never heard of melanoma (odds ratio 1.33, 95% CI 1.03-1.72). Females were more knowledgeable than males (odds ratio 1.74, 95% CI 1.26-2.22), but continued to sunbathe. Teenagers and young adults tended to be relatively ignorant of melanoma, and were less likely to protect themselves against sunburn while sunbathing than other age groups. Teenagers, young adults, and males need to be targeted more effectively in future publicity campaigns. Furthermore, many people who know about melanoma continue to put themselves at risk by sunbathing. New strategies need to be developed to influence behaviour as well as increasing awareness.

Grin CM; Pennoyer JW; Lehrich DA; Grant-Kels JM
Department of Medicine, University of Connecticut School of Medicine, Farmington.
Pediatr Dermatol (United States) Dec 1994, 11 (4) p304-9

Sun exposure in childhood has been implicated as a risk factor for the development of melanoma and nonmelanoma skin cancers. As an increasing number of young children are cared for in day-care centers, we were interested in examining the sun-protection practices in this setting. In our study of day-care centers, we found that while most day-care center staff were aware of the adverse effect of excess sun exposure and the need for sun protection, the use of sunscreen and protective clothing and avoidance of midday sun were limited. We conclude that intensive education of day-care center staff and parents regarding sun exposure and sun protection is necessary if we are to attempt to reduce the frequency of melanoma and nonmelanoma skin cancer.

Campbell HS; Birdsell JM
Division of Epidemiology and Preventive Oncology, Alberta Cancer Board, Calgary, Canada.
Prev Med (United States) Mar 1994, 23 (2) p160-6

BACKGROUND. There is considerable evidence that exposure to ultraviolet radiation increases the risk of many dermatologic conditions including nonmelanoma skin cancers and the more serious cutaneous malignant melanoma . Despite this, there is little data on healthy persons' exposure patterns and protection behaviors.

METHODS. As part of a larger survey for a cancer prevention demonstration program, a household survey of 3,843 adults ages 35-64 was conducted in four mid-size cities in Alberta, Canada. Self-administered questionnaires were used to collect data on sun-related knowledge, beliefs, occupational and recreational exposure and current protective behaviors.

RESULTS. Only 45% of respondents believed sun exposure affected their chances of getting cancer. With few exceptions, less than 50% of either sex were likely to routinely use any of the four protective measures: avoiding the sun, protective clothing, hats, or sunscreen . This propensity was inadequate even for those with sun-sensitive skin types. Men and women differed in the type of protection preferred. Older adults were more likely to take precautionary measures.

CONCLUSIONS. There is clearly a need for modification of the public's beliefs and protective behaviors if the predicted skin cancer epidemic is to be avoided. Knowledge of protective behaviors and age- and gender-specific preferences will help in planning future research and health education programs.

Wolf P; Donawho CK; Kripke ML
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Natl Cancer Inst (United States) Jan 19 1994, 86 (2) p99-105

BACKGROUND: Epidemiologic evidence suggests that exposure to UV radiation plays a significant role in the development of melanoma skin cancers. As early surgical removal of the melanoma is the only effective therapy, current strategies for reducing mortality from melanoma focus on prevention of the disease. Chemical sunscreens protect mice from development of skin cancers that resemble sunlight-induced human squamous cell cancers, but there appears to be a complex relationship between UV radiation exposure and development of melanoma .

PURPOSE: We asked whether common sunscreens would protect mice against UV radiation-induced enhancement of melanoma incidence.

METHODS: C3H mice were exposed to 4.8 kJ/m2 UVB from FS40 sunlamps twice a week for 3 weeks. Sunscreens containing 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-amin obenzoate, 6% benzophenone-3, or the oil-in-water vehicle alone were applied to the ears and tails of the mice 20 minutes before irradiation. At various times during and after exposure, we determined UV radiation-induced inflammation by measuring ear swelling. We also examined the ears histologically for UV radiation-induced alterations. One day after the final irradiation, 2.5 x 10(4) syngeneic K1735 melanoma cells were injected into the external ears. Mice were examined weekly for tumor growth for 5-8 weeks after tumor cell injection. Control mice were treated in the identical way except for exposure to UV radiation.

RESULTS: The incidence of melanomas was significantly higher in the UV-irradiated mice. All three sunscreens protected against UV radiation-induced ear swelling and clearly diminished histopathologic alterations, including sunburn cell formation, epidermal hyperplasia, and mononuclear cell infiltrate in the dermis. However, the sunscreens failed to protect against UV radiation-induced increase in melanoma incidence. The sunscreens or vehicle alone did not significantly alter tumor growth.

CONCLUSIONS: Protection against sunburn does not necessarily imply protection against other possible UV radiation effects, such as enhanced melanoma growth.

IMPLICATIONS: Sunscreen protection against UV radiation-induced inflammation may encourage prolonged exposure to UV radiation and thus may actually increase the risk of melanoma development. These findings suggest that further research on the ability of sunscreens to prevent melanoma is urgently needed.

Continued on the next page...

Garland CF; Garland FC; Gorham ED
Department of Community and Family Medicine, University of California at San Diego, La Jolla 92138-0631.
Ann Epidemiol (United States) Jan 1993, 3 (1) p103-10

Incidence rates of melanoma have risen especially steeply since the mid-1970s. The two principal strategies for reduction of risk of melanoma and other skin cancers are sun avoidance and use of chemical sunscreens. Rising trends in the incidence of and mortality from melanoma have continued since the 1970s and 1980s, when sunscreens with high sun protection factors became widely used. Commonly used chemical sunscreens block ultraviolet B (UVB) but are virtually transparent to ultraviolet A (UVA), which makes up 90 to 95% of ultraviolet energy in the solar spectrum. Because sunscreens prevent erythema and sunburn, and inhibit accommodation of the skin to sunlight, their use may permit excessive exposure of the skin to portions of the solar spectrum other than UVB. If melanoma and basal cell carcinoma are initiated or promoted by solar radiation other than UVB, as laboratory data suggest, then UVB sunscreens might not be effective in preventing these cancers, and sunscreen use might increase the risk of their occurrence. Alternative explanations for the rapid rise in the incidence and mortality rates of melanoma , such as changes in patterns of recreational sun exposure, are discussed. Traditional means of limiting overexposure to the sun, such as wearing of hats and adequate clothing and avoidance of prolonged sunbathing, may be more prudent than reliance on chemical sunscreens. (94 Refs.)

Hill D; White V; Marks R; Borland R
Centre for Behavioural Research in Cancer, Anti-Cancer Council of Victoria, Carlton South, Australia.
Eur J Cancer Prev (England) Nov 1993, 2 (6) p447-56

This study aimed to determine trends in exposure to sunlight in the context of a melanoma prevention programme by monitoring the prevalence of sunburn and sun-related attitudes and behaviours. Telephone interviews were conducted in a baseline summer (December 1987 to February 1988) and two subsequent summers after the introduction of the SunSmart health promotion campaign. Interviewing a sample of 4,428 adult residents of the Australian city of Melbourne took place throughout summer on Monday evenings. Behavioural and sunburn data were reported for the previous weekend and relevant attitudinal data were collected. After adjusting for ambient ultraviolet radiation levels and temperature, survey month, age, sex and skin type, a significant reduction in sunburn was found. The crude proportion of sunburnt dropped from 11% to 10% to 7% over 3 years and the adjusted odds ratios (and 95% confidence intervals) were as follows: Year 1/Year 2; 0.75 (CI 0.57-0.99) and Year 1/Year 3; 0.59 (CI 0.43-0.81). Substantial attitudinal shifts occurred over the 3 years. Hat wearing increased significantly each year (19%, 26%, 29%), as did sunscreen use (12%, 18%, 21%). However, the trends in mean proportion of body surface area covered by clothing were less clear cut (0.67, 0.64, 0.71). It is concluded that melanoma risk factor exposure of populations can change fairly rapidly and that well-conducted health promotion campaigns can play a part in producing such change.

Hughes BR; Altman DG; Newton JA
Department of Dermatology, Royal London Hospital, U.K.
Br J Dermatol (England) Apr 1993, 128 (4) p412-7

The effectiveness of an education package for secondary schools about the sun and skin cancer was assessed using questionnaires. A variety of teaching methods was used, including pamphlets, workbooks, and a video. The effect of this material was assessed by asking pupils to complete questionnaires immediately after receiving the package (July), and after the summer holiday (September). Five-hundred and forty-three children from seven schools were recruited into the study. Results of the questionnaire demonstrated a significant difference in knowledge (P < 0.001) and reported attitude (P < 0.001) compared with a control group. There was no significant difference in behaviour of the taught groups compared with the control group. The only significant activity associated with increased knowledge was wearing a sunscreen (P < 0.005). In contrast, in terms of attitude, those who covered up in the sun (P < 0.0001), wore a sunscreen (P < 0.004), and sat in the shade (P < 0.02), had significantly better attitudes than those who did not behave in this way. This project is a first attempt to assess health education in schools, and reports changes in knowledge, attitudes, and some aspects of behaviour. Adolescents are a group who are difficult to influence, but our study has produced some useful information about how these children respond to such teaching measures.

Ainsleigh HG
Prev Med (United States) Jan 1993, 22 (1) p132-40

For more than 50 years, there has been documentation in the medical literature suggesting that regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests that this is a causal relationship that acts through the body's vitamin D metabolic pathways. The studies reviewed here show that (a) sunlight activation is our most effective source of vitamin D; (b) regular sunlight/vitamin D "intake" inhibits growth of breast and colon cancer cells and is associated with substantial decreases in death rates from these cancers; (c) metabolites of vitamin D have induced leukemia and lymphoma cells to differentiate, prolonged survival of leukemic mice, and produced complete and partial clinical responses in lymphoma patients having high vitamin D metabolite receptor levels in tumor tissue; (d) sunlight has a paradoxical relationship with melanoma , in that severe sunburning initiates melanoma whereas long-term regular sun exposure inhibits melanoma ; (e) frequent regular sun exposure acts to cause cancers that have a 0.3% death rate with 2,000 U.S. fatalities per year and acts to prevent cancers that have death rates from 20-65% with 138,000 U.S. fatalities per year; (f) there is support in the medical literature to suggest that the 17% increase in breast cancer incidence during the 1991-1992 year may be the result of the past decade of pervasive anti-sun advisories from respected authorities, coinciding with effective sunscreen availability; and (g) trends in the epidemiological literature suggest that approximately 30,000 U.S. cancer deaths yearly would be averted by the widespread public adoption of regular, moderate sunning.(ABSTRACT TRUNCATED AT 250 WORDS) (43 Refs.)

Hill D; White V; Marks R; Theobald T; Borland R; Roy C
Centre for Behavioural Research in Cancer, Anti-Cancer Council of Victoria, Carlton South, Australia.
Prev Med (United States) Sep 1992, 21 (5) p654-69

BACKGROUND. To determine the independent contribution of behavioral factors to the occurrence of sunburn, sun protection behavior was assessed over 13 successive summer weekends in a total of 1,655 adults in Melbourne, Australia.

METHODS. Telephone survey respondents provided detailed accounts of activities engaged in, time spent outside, and hat, clothing, and sunscreen coverage in the 4 hr around the solar midday on both weekend days, as well as skin type, sociodemographic descriptors, and degree of sunburn experienced. Independent measures of atmospheric temperature and ambient ultraviolet radiation (UVR) were added to individual records.

RESULTS. The (mostly recreational) weekend sunburn in this urban sample was strongly associated with UVR, as expected. Temperature at 3 PM, sensitive skin type, youthfulness, and being male were also independently associated with sunburn. After all other predictors were controlled for, the body exposure index (which took into account time outside and hat, clothing, and sunscreen coverage) made a strong independent contribution to the explanation of sunburn (P < 0.001).

CONCLUSION. It was concluded that behavior change strategies to prevent malignant melanoma of the skin are warranted.

McGee R; Williams S
Hugh Adam Cancer Epidemiology Unit, University of Otago Medical School, Dunedin.
N Z Med J (New Zealand) Oct 14 1992, 105 (943) p401-3

AIM: to examine adolescents' sun behaviours and use of sun protection measures, attitudes to tanning, and awareness of melanoma , in the light of the Cancer Society's Sun-smart campaign in the summer of 1990-1.

METHODS: a sample of 345 fourth formers from schools in Auckland, Wellington and Christchurch was surveyed regarding their experiences and beliefs about tanning, and their use of sun protection measures including sunblock lotions, hats and clothing; their knowledge of melanoma and risks for melanoma ; and their exposure to the educational campaign and its message.

RESULTS: despite relatively high awareness of melanoma as a dangerous form of cancer, a significant proportion of the sample showed high positive attitudes towards tanning and high levels of sun exposure without adequate sun protection. On the positive side, reports of exposure to sources of information about melanoma were correlated with melanoma awareness, which in turn predicted use of sun protection measures.

CONCLUSION: the findings suggest that campaigns such as those of the Cancer Society have an important role to play in reducing high levels of sun exposure among adolescents. Continued efforts need to be directed at adolescents to increase the acceptability and use of sun protection measures.

Berwick M; Fine JA; Bolognia JL
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06510.
Prev Med (United States) May 1992, 21 (3) p302-10

BACKGROUND. In May 1988, a community skin cancer screening was held, and of the 251 individuals who attended, 214 (85%) completed a follow-up questionnaire. The objective of this study was to examine the associations among attitudes, knowledge, and behavior in those who had attended the screening.

RESULTS. Analysis showed that females were twice as likely to have false positive screening diagnoses as males (odds ratio 2.2; P = 0.06). Attitudes toward tanning were not correlated with knowledge about the harmful effects of excess sun exposure (rp = -0.02; P = 0.67) or with behaviors such as reported sun exposure (for positive attitude versus "poor" attitude, linear trend P less than 0.11) and sunscreen use (linear trend P = 0.70). Behavior, defined as reported sunscreen use, was highly correlated with knowledge, both of the harmful effects of the sun and of the definition of SPF (linear trend P less than 0.001). Sunscreen use was also associated with the younger age group (those less than 59, P less than 0.05), female sex (P less than 0.001), higher education (P less than 0.05), and perceived risk for melanoma (P less than 0.05).

CONCLUSIONS. We conclude that more targeted education in the domain of knowledge would benefit males and those over the age of 59.

Weinstock MA; Stampfer MJ; Lew RA; Willett WC; Sober AJ
Dermatoepidemiology Unit, VA Medical Center, Providence, RI 02908.
J Invest Dermatol (United States) May 1992, 98 (5) p809-11

The rapid increase in melanoma incidence and mortality has given rise to nationwide and international campaigns that encourage the public to protect themselves from solar radiation with clothing, sunscreens, and other measures. The basis of these campaigns has been challenged by proponents of the theory that vitamin D, which is generated in the skin by ultraviolet B radiation, inhibits the development of melanoma . The present investigation tests this theory by examining the relation between dietary vitamin D and melanoma risk in a case-control study. Vitamin D intake was assessed by a food-frequency questionnaire in 165 melanoma patients and 209 controls. After controlling for age, hair color, and family history of melanoma , there was no association of melanoma risk with total vitamin D intake, calorie-adjusted vitamin D intake, vitamin D intake from foods, or consumption of milk or vitamin D supplements. We find no evidence to suggest that vitamin D protects against melanoma , and therefore continue to support the ongoing public health campaigns aimed at reducing sun exposure for the prevention of melanoma .

Truhan AP
Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Clin Pediatr (Phila) (United States) Dec 1991, 30 (12) p676-81
[corrected and republished article originally printed in Clin Pediatr (Phila) 1991 Jul;30(7):412-21]

There is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of sun exposure on the skin. Studies indicate that excessive sun exposure during the first 10-20 years of life greatly increases the risk of skin cancer. Nonmelanoma skin cancer (basal cell and squamous cell carcinoma) has been associated with cumulative sun exposure, whereas melanoma has been associated with short, intense sun exposure or blistering sunburn. Under normal circumstances, children receive three times the annual sun exposure of adults; most of one's lifetime sun exposure occurs in childhood. Depletion of the earth's protective ozone layer adds to the photodamage problem. It is clear that sun protection is most vital in the early years. Those with fair skin are at highest risk. Photoprotective measures including sunscreen , clothing, and sun avoidance in childhood may significantly reduce the occurrence of melanoma and other skin cancer in later life. Regular use of sunscreen with a sun protection factor of 15 during the first 18 years of life could reduce the lifetime incidence of nonmelanoma skin cancer by 78%. Pediatricians can play a major role in educating parents and children. (27 Refs.)

O'Donoghue MN
Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.
Dermatol Clin (United States) Oct 1991, 9 (4) p789-93

It is hoped that this review has given some information to direct the clinician in his approach to his patients. Certainly, we would desire that the incidence of malignant melanoma as well as other skin cancers would start to decrease. (46 Refs.)

Crutcher WA; Cohen PJ
Children's Hospital of San Franscisco, California.
Am Fam Physician (United States) Aug 1990, 42 (2) p372-85

The incidence of melanoma has been steadily increasing, with a trend for this tumor to develop at younger ages. The only satisfactory treatment for melanoma is early intervention; therefore, routine screening for melanoma and dysplastic nevi during the general physical examination is important. The prevalence of dysplastic nevi is estimated to be 2 to 5 percent. Patients with dysplastic nevi appear to have at least a 6 percent lifetime risk of melanoma . In the most severely affected patients (those with a family history of dysplastic nevi and more than one melanoma), the lifetime risk may exceed 50 percent. Patients with dysplastic nevi merit periodic follow-up. Since these nevi tend to be familial, close relatives of affected patients may also benefit from a screening examination. Individuals at increased risk for melanoma may display one or more of the following risk factors: dysplastic nevi, freckling, tendency to sunburn and numerous common nevi. Such individuals may benefit most from education in sunburn avoidance, sunscreen use and self-examination for changing nevi. A better informed public and heightened physician awareness are the most effective means of reducing mortality from this virulent malignancy. (35 Refs.)

Hersey P; MacDonald M; Burns C; Schibeci S; Matthews H; Wilkinson FJ
J Invest Dermatol (United States) Mar 1987, 88 (3) p271-6

Previous studies in rodents have shown that ultraviolet radiation (UVR) may have direct effects on the immune system in the skin and at higher doses may induce systemic suppression of immune responses. We have previously shown that UVR from sun or solarium beds may induce systemic effects in human subjects. The purpose of the present study was to examine whether these systemic effects in human subjects could be prevented by use of commercially available sunscreen agents. Groups of 12 normal subjects were exposed to radiation from solarium lamps after application of a sunscreen agent or the base used in its preparation. Twelve half-hourly exposures induced a depression of natural killer (NK) cell activity against a melanoma and the K562 target cell which was not prevented by use of the sunscreen agent. Changes in functional activity were accompanied by a reduction in NK cell numbers assessed by Leu-11 monoclonal antibodies against the labile Fc receptor. Application of the sunscreen agent also did not protect against effects of solarium exposure on recall antigen skin tests and immunoglobulin production in vitro in pokeweed mitogen-stimulated cultures of B and T cells. These results suggest that further evaluation of the wave-length spectrum of UVR and the effectiveness of sunscreen agents in prevention of UVR-induced effects on the immune system is needed.

JAMA (United States) Jul 21 1989, 262 (3) p380-4

Tanning for cosmetic purposes by sunbathing or by using artificial tanning devices is widespread. The hazards associated with exposure to ultraviolet radiation are of concern to the medical profession. Depending on the amount and form of the radiation, as well as on the skin type of the individual exposed, ultraviolet radiation causes erythema, sunburn, photodamage (photoaging), photocarcinogenesis, damage to the eyes, alteration of the immune system of the skin, and chemical hypersensitivity. Skin cancers most commonly produced by ultraviolet radiation are basal and squamous cell carcinomas. There also is much circumstantial evidence that the increase in the incidence of cutaneous malignant melanoma during the past half century is related to increased sun exposure, but this has not been proved. Effective and cosmetically acceptable sunscreen preparations have been developed that can do much to prevent or reduce most harmful effects to ultraviolet radiation if they are applied properly and consistently. Other safety measures include (1) minimizing exposure to ultraviolet radiation, (2) being aware of reflective surfaces while in the sun, (3) wearing protective clothing, (4) avoiding use of artificial tanning devices, and (5) protecting infants and children. (30 Refs.)

Scotto J; Fears TR
Biostatistics Branch, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Invest (United States) 1987, 5 (4) p275-83

Using recent data from cancer incidence surveys and measures of UVB exposure levels at seven geographic locations within the United States, we estimate the dose-response relation between UVB and skin melanoma incidence. Mathematical models used information from general population interview studies conducted in these locations to adjust for potentially confounding factors such as age, skin color, ancestry, eye color, hair color, sunburn sensitivity, prevalence of moles, freckles, and hours spent outdoors, use of sunscreen /lotion, and other variables. The effect of geographic UVB exposure on incidence was found to be statistically significant (p less than 0.01) after adjusting for each variable and certain combinations of these variables. We found that incidence rates for those skin melanomas arising in the face, head, neck, or upper extremities (i.e, the most exposed sites) were more sensitive to UVB increases than the incidence rates for those lesions occurring in the ordinarily less exposed sites of the trunk and lower extremities.

Stern RS; Weinstein MC; Baker SG
Arch Dermatol (United States) May 1986, 122 (5) p537-45

Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care.

Azizi E; Kushelevsky AP; Schewach-Millet M
Isr J Med Sci (Israel) Jul 1984, 20 (7) p569-77

The sun protection factors (SPF) of 35 commercially available sunscreen preparations were tested on human skin under various conditions. Five distinct groups of products, ranging from minimal (SPF 2 to less than 4) to ultra sun protection (SPF 15 to greater than 19) were evaluated. Claimed SPF values were not always consistent with those obtained in our tests. Substantivity studies of a randomly selected group of sunscreen preparations during the hot, highly humid Israeli summer showed mean SPF reductions of 47 and 60%, respectively, following exercise-induced sweating or a 20-min swim. Judicious selection and use of an appropriate sunscreen preparation according to individual skin type or life-style, as well as the introduction of strict testing and labeling regulations, are essential measures for reducing the risk of sun-induced skin cancer and malignant melanoma in Israel.

Hillhouse J.J.; Stair III A.W.; Adler C.M.
J.J. Hillhouse, Department of Psychology, East Tennessee State University, Box 70,649, Johnson City, TN 37614 United States
Journal of Behavioral Medicine (United States) 1996, 19/6 (543-561)

Sunbathing and sunscreen use, as well as related intentions, attitudes, beliefs, and knowledge, were assessed in 90 Southern Appalachian undergraduates. A large majority (75%) reported sunbathing; with more than half reporting sun lamp use. A slight majority (56.7%) reported some use of sunscreen . Subjects reporting an intention to tan spent more time sunbathing, both outside and under a sun lamp. Individuals reporting a sun protection intention had lighter tans and spent less time sunbathing. Sunbathing was predicted by perceptions of sunbathing as relaxing, while sun lamp use was predicted by more positive views of suntans. Sunscreen use was predicted by more positive sun protection attitudes and less negative sunscreen attitudes.

Woodruff J.
Manufacturing Chemist (United Kingdom) 1996, 67/10 (79-81)

Skin cancer is increasing in frequency, and using sun protection products has never been more important. John Woodruff looks at efficacy improving suncare formulation developments.

Richard M.A.; Grob J.J.
Service de Dermatologie, Hopital Sainte Marguerite, 270 Bd de Sainte Marguerite,F-13277 Marseille Cedex 9 France
Aktuelle Dermatologie (Germany) 1996, 22/Suppl. 2 (93-96)

Photoprotection is an important prophylaxis against sun burn, photodermatoses, light-induced, premature aging of the skin, and especially against the increasing numbers of skin neoplasms. Aside from the individual constitution and other 'environmental' factors, the role of solar radiation in the etiology of skin tumors is undisputed. According to epidemiological studies, frequent and excessive exposure to sunlight, such as for example, sunburn with the formation of blisters influences the risk of melanoma whereas the cumulative solar radiation received during life appears to be responsible for the formation of carcinoma. According to estimates, about 25% of the total exposure to solar radiation occurs during childhood and adolescence. It is thus important to provide prophylactic information adapted to the respective target group (children, adolescents, adults). The major objective of such information should be to emphasize the risks of excessive and cumulated exposure to sunlight, to adjust exposure to the individual tolerance for sunlight, and to encourage changes in behavior and clothing instead of the use of an insufficient suntan cream. This information should be distributed by general practitioners and the news media in nation-wide campaigns.

Linge C.
RAFT Institute of Plastic Surgery, Mount Vernon Hospital,Northwood, Middlesex HA6 2RN United Kingdom
Cancer Surveys (United States) 1995, 26/- (71-88)

The constitutional pigmentation characteristics of black skin provide a strong sunscreen , filtering out the vast majority of UV radiation that reaches the melanocytes. In addition, at a cellular level, the high melanin content and enhanced free radical modulating systems seen in the melanocytes of black skin provide further protection from UV radiation induced damage and presumably mutagenesis. By contrast, the low melanin content of both non-tanned white skin and their melanocytes provides little if any sunscreen protection. Instead, the variation in susceptibility to melanoma among white skinned people may depend on other factors, which include the ratio of photoprotective eumelanin to potentially phototoxic phaeomelanin, the status of the anti-oxidant systems, the level of photosensitizer molecules and the efficacy of DNA repair and associated mechanisms.

Marks R.
Department of Medicine (Dermatology), University of Melbourne, St. Vincent's Hospital,Fitzroy, Vic. Australia
Ca-A Cancer Journal for Clinicians (United States) 1996, 46/4 (199-216)

Incidence and mortality rates for melanoma have been rising steadily during the 20th century. Primary prevention and early detection are the two major public health approaches now being considered or undertaken to decrease mortality. This article reviews both approaches, outlining the data and assumptions on which the approaches are based and giving examples of program development, delivery, and measurement of outcome.

Amblard P.
Hopital La Tronche, Service de Dermatologie,38043 Grenoble Cedex France
Nouvelles Dermatologiques (France) 1996, 15/5 (349-353)

External photoprotection is still a topical subject, and the controversy surrounding sunscreens is not yet resolved. The essential question remains: do sunscreens prevent or on the contrary put the user at risk of developing skin cancer? A recent epidemiological Swedish study concludes that sunscreens do not protect from malignant melanoma . On the other hand, it has been said that the persons who spend the longest time in the sun are the same who frequently use sunscreens. This is contradicted by a Danish study which asserts that sunscreen use does not prolong sun exposure. On the contrary, one study in animals and another in man tend to prove that the use of large spectrum sunscreens prevents the appearance of contact photoimmunosuppression which seems to be an important factor in photocarcinogenesis as well as in photoaging. This shows the importance of UVA in the genesis of sun induced skin lesions. A recent Lavker study shows the importance of UVA1 (340-400 nm). A Harth study confirms the bad utilisation of sunscreens whereas Bohm puts the light on the possible ill effects of titan dioxide. On the other hand, a number of recent substances applied on the skin have been shown to have a sunscreen effect: DHA (Moyal), N-acetyl-cysteine (Van Den Broeke), green tea polyphenols (Katiyar), selenium and thiol compound association (Emonet). Three studies concern tocopherol. The Bisset research team showed that tocopherols sorbate was more active that alpha tocopherol. The de Vries research team showed that tocopherol's acetate was a pro drug which transforms itself very slowly in active tocopherol and that is why Gers-Barlag suggested to add to it fural glucitol whose photoprotective action is very fast (1/2 hour) but ephemeral (12 hours). Internal photoprotection is becoming a topical subject because it is not anymore only indicated in photodermatosis. Black confirmed the fact that a diet poor in fat lowers the incidence of solar keratosis and of carcinomas and Rhodes showed the protective effect of fish oil at very high doses. On the other hand, the Gilchrest research team did not find any protective action on sunburn cells neither from beta-carotene nor from tocopherol. This question whether oral intake of free radical scavengers to prevent photoaging and skin cancer is of interest. Although one can certainly propose a cocktail of these agents, further investigations are needed in order to confirm their utility.

Raab W.
Walfischgasse 3,A-1010 Wien 1 Austria
Aktuelle Dermatologie (Germany) 1996, 22/Suppl. 1 (2-6)

Ultraviolet-induced skin lesions may be provoked via different mechanisms. Most frequently, an overload of the natural sun defense is encountered, resulting in sunburn - seen immediately - or in chronic sun damage emerging only after decades. With the increasing life expectancy, the symptoms of such a chronic sun damage are more and more often noticed by the dermatologist (skin dryness, premature skin ageing, pigmented spots, actinic keratoses, non-melanoma skin cancer). Other sun-induced skin lesions include specific dermatoses caused by ultraviolet rays ('sun-Kobner'), the consequences of immunosuppression (Herpes simplex 'solaris', LE, melanoma) and photodynamic reactions due to, for example, various drugs. True photodermatoses are only rarely seen, possibly due to the fact that their diagnosis is rather complicated and mild cases are misdiagnosed. - Sun protection in general and even more in the ever - increasing cases of pathological sun reactions is one of the most important tasks of the dermatologist. Problems of pigmentation, physical and chemical sun protection, strength of the sun protection 'factor' (effective only up to 60% of the erythema threshold dose!) must be discussed with the patient exhibiting sun-induced skin lesions or just asking for advice.

Buchner S.A.
Dermatologische Universitatsklinik, Kantonsspital, Petersgraben 4,CH-4031 Basel Switzerland
Aktuelle Dermatologie (Germany) 1996, 22/Suppl. 1 (7-12)

Clinical, epidemiologic, and experimental evidence strongly supports the relationship between chronic sunlight exposure, UV-induced damage of the skin and nonmelanocytic skin cancers. Although UVB is the major causative action spectrum for sunlight-induced skin damage and nonmelanoma skin cancers, UVA is also implicated being shown to induce DNA damage. Cumulative sun exposure is thought to reduce the cell capacity to repair DNA damaged by UV radiation. Absent or deficient DNA repair may lead to different point mutations which are responsible for the majority of actinic changes, malignant cell clone formation, and appear to be most relevant in the development of UV-induced nonmelanoma skin tumors. The clinical spectrum of actinic damage due to the cumulative sunlight exposure includes wrinkling, furrowing, actinic elastosis, irregular pigmentation, and teleangiectasia. On the sunlight-damaged skin frequently occur precancerous skin lesions, basal cell carcinomas, squamous cell carcinomas, and lentigo maligna-melanoma . Early detection of precursors to skin cancer as well as primary prevention programs educating all age groups of the population about the risks of excessive sun exposure, and the regular use of sunscreens are needed in order to reduce the incidence of skin cancer.

Wentzell J.M.
Billings Clinic, 2825 8th Ave. N.,Billings, MT 59107-5100 United States
American Family Physician (United States) 1996, 53/5 (1713-1719)

Sun exposure is linked to visible signs of skin aging, skin cancer, photodermatoses, exacerbation of systemic disease and photoallergic, as well as phototoxic, drug eruptions. Sunscreens very considerably in their ability to protect patients from exposure to ultraviolet light and its effects. Inappropriate choice and use of sunscreen products can lead to worse problems than using no sunscreen at all. Controversies about sunscreen include adequate level of sun protection factor, appropriate age of users, and whether use of sunscreen products can prevent skin cancer. Instructing patients in how to select end use sunscreen can help prevent or mitigate a variety of cutaneous end systemic diseases.

Koh H.K.; Geller A.C.; Miller D.R.; Grossbart T.A.; Lew R.A.
Boston University School of Medicine, 80 E Concord St,Boston, MA 02118 United States
Archives of Dermatology (United States) 1996, 132/4 (436-442)

Skin cancer represents an increasingly urgent worldwide public health problem. Estimates project almost a million (or more) new cases each year in the United States; this number is roughly equal to that of all other cancers combined. The incidence of cutaneous melanoma , which is mounting faster than that of any other cancer in white persons, nearly doubled from 1973 to 1990; in addition, the rise in melanoma mortality rates in white persons ranks second only to lung cancer. While the overall 5-year melanoma survival rates in the United States rose from 49% (in the early 1950s) to 82% (in the early 1990s), death rates more than doubled during the same time; these rates were driven up by the rising incidence. This year in the United States, melanoma will strike 34 000 persons and kill 7200-part of an estimated 90 000 cases diagnosed worldwide. Despite exciting advances in innovative treatment approaches (eg, immunotherapy and gene therapy), metastatic melanoma remains largely incurable. Decades of research have not only crystallized an understanding of the epidemiology, risk factors, and natural history of skin cancer but also have begun to stimulate international efforts to promote its prevention and control. In theory, the public health burden of melanoma and skin cancer could be lowered through some combination of effective primary and secondary prevention measures. Reduction of excessive sun exposure (primary prevention) could theoretically reduce the incidence, since experts hypothesize that 90% of the cases of nonmelanoma skin cancer (NMSC) and two thirds of the cases of melanoma may be attributed to excessive sunlight exposure. Primary prevention strategies can include personal behavior changes for individuals (eg, minimizing UV exposure and using sunscreen), as well as policy and environmental interventions for populations (eg, provision of shady areas and preservation of the ozone layer). Early detection (secondary prevention) should increase melanoma cure rates, since long-term survival figures of 92% for localized melanoma decline sharply to lower than 5% for metastatic disease. Furthermore, these external, visible cancers have identifiable risk factors, should be readily recognizable by the public and health professionals alike, and are easily treated in the early stages. We summarize the current state of melanoma and skin cancer control around the world.

Koh H.K.
Cancer Prevention and Control Center, Boston University School of Medicine, 80 E. Concord Street C-324,Boston, MA 02118 United States
Environmental Health Perspectives (United States) 1995, 103/Suppl. 8 (255-257)

Ultraviolet (UV)-associated cancer is the most common cancer in the United States. Approximately 90% of nonmelanoma skin cancer and 65% of melanoma are attributable to UV exposure and theoretically could be eliminated by primary prevention measures. Safe sun strategy includes use of sunscreens, use of protective clothing, minimization of exposure from 10 A.M. to 3 P.M., and avoidance of tanning parlors. Although more definitive data in human populations on the effectiveness of sunscreens to prevent melanoma and skin cancer are needed, sunscreens are thought to reduce risk. Safe sun prevention must start in childhood and adolescence when people receive most of their UV exposure. Secondary prevention through professional and public education and early detection may further reduce melanoma mortality.

Weinstock M.A.
Dermatoepidemiology Unit, VA Medical Center 111D, 830 Chalkstone Avenue,Providence, RI 02908-4799 United States
Environmental Health Perspectives (United States) 1995, 103/Suppl. 8 (251-254)

Sun exposure has now been established as the most important avoidable cause of nonmelanoma skin cancer (NMSC) and melanoma . With specific reference to melanoma , there are several key issues that remain to be resolved. These include definition of the action spectrum, the importance of systemic effects of sun exposure, whether a tan is protective, the risk of tanning booth exposures, and the efficacy of sunscreens. Also the role, if any, of sun exposure in noncutaneous malignancies remains to be established. Melanoma incidence and mortality have increased dramatically over the past several decades, but these increases have now slowed, and for mortality among those 15 to 45 years of age, decreasing rates are now observed. Improving the coverage of the Surveillance, Epidemiology, and End Results (SEER) registries by requiring pathology laboratories in non-SEER areas to report cancers among SEER area residents will allow correct interpretation of these trends in the future at minimal cost. The available data on trends in NMSC incidence and mortality are suboptimal but suggest a pattern of declining mortality despite increasing incidence. Trends in NMSC morbidity have not been defined. Establishing NMSC registries in a few diverse sentinel areas would allow more reliable inference and monitoring. Techniques are being developed for reducing sun exposures and increasing early detection of skin cancers in the general population, but improved monitoring of incidence, mortality, and morbidity is required to monitor the effects of current and future ozone depletion and to evaluate prevention and early detection measures.

Runger T.M.
Hautklinik und Poliklinik, Georg-August Universitat, Abteilung Dermatologie-Venerologie, von-Siebold Strasse 3,37075 Gottingen Germany
H+G Zeitschrift fur Hautkrankheiten (Germany) 1995, 70/12 (877-881)

Mutations following UV-induced DNA damage represent the genetic cause of UV-induced malignant tumors of the skin. Different wavelengths of ultraviolet radiation possess different biological effects. UVA, as well as UVB, is capable to induce malignant epithelial tumors. However, UVA might be more important in the induction of malignant melanoma . UVA and UVB generate different kinds of DNA damage. UVB is able to exite the DNA molecule directly, whereby it generates pyrimidine dimers. Longerwave UV candamage the DNA molecule only indirectly. In that case another molecule, a so-called photosensitizer is exited and then transfers its energy or electrons onto the DNA. Many of these reactions are mediated by reactive oxygen species, mainly singlet oxygen. Predominantly purine base modifications entail. Directly and indirectly UV-induced DNA damage is processed differently by cellular DNA repair systems, generating different mutations. Oxidative, photosensitizer-mediated DNA damage by UVA offers a molecular explanation for the observations of genotoxic, mutagenic, and carcinogenic effects of UVA. In order to prevent malignant tumors of the skin, especially malignant melanoma , a protection against UVA should be included.

Duarte A.M.
Miami University School of Medicine, PO Box 016250,Miami, FL 33101 United States
Current Opinion in Pediatrics (United States) 1995, 7/4 (423-430)

Recently interest in the potential impact of the environment on our general health has heightened. Particular focus has been directed toward environmental skin injuries because the integument, the only organ of the body that is constantly exposed to the surrounding environment, directly demonstrates the damaging effects of the environment and thereby allows for direct visual recognition by both physicians and laypersons. The characteristic cutaneous features, physiologic responses, therapeutic approaches to promote healing, and preventive measures that may be taken to avoid future environmental injury are discussed. The scope of environmental injuries to the skin is extremely vast; therefore, the focus of this review is limited to cutaneous injuries that may result as a consequence of ultraviolet irradiation, marine life, and electrical forces.

Marks R.; Kopf A.W.
Department of Medicine, University of Melbourne, St. Vincent's Hospital,Fitzroy, Vic. 3065 Australia
International Journal of Dermatology (Canada) 1995 , 34/7 (445-447)

One can confidently predict that the 21st century will be a span of intense activity in unraveling the precise molecular and biochemical events that lead to the various forms of cutaneous cancers. These discoveries will lead to new approaches in our therapeutic armamentarium that currently do not exist. Eventually, the incidence rates and mortality rates from cancers of the skin will markedly decline-the finite goal of all the combined endeavors of the scientific and practicing medical community.

Zinman R.; Schwartz S.; Gordon K.; Fitzpatrick E.; Camfield C.
Izaak Walton Killam Children's Hosp., 5850 University Ave,Halifax, NS B3J 3G9 Canada
Archives of Pediatrics and Adolescent Medicine (United States) 1995, 149/7 (804-807)

Objective: To identify risk factors predictive of sunscreen use in children.

Design: Cross-sectional review of convenience sample.

Setting: Emergency department of a regional referral pediatric hospital. Subjects: Nine hundred twenty-five parents of children presenting to the emergency department in August 1993.

Main Outcome Measures: Parental risk factors assessed were use of sunscreen , tanning behaviors, previous blistering sunburn, knowledge of cancer risk related to sunburn and sun protection factor definition, education level, and other health-promoting behaviors. The parents were asked about perceived risk for their child's being sunburned in the next month or development of skin cancer in their lifetime, as well as an estimation of safe sun exposure time for their child. Child risk factors included a history of previous painful sunburn and parental assessment of their child's skin type based on susceptibility to sunburn.

Results: Eighty- four percent of parents reported that their children had used sunscreen at least once in the previous 2 months. The use of sunscreen in children younger than 1 year was 54%, from 1 to 12 years of age was 91%, and older than 12 years was 68%. Factors associated with increased likelihood of sunscreen use were age of 1 to 12 years, parental use of sunscreen , estimation of safe sun exposure of less than 30 minutes, description of child skin type as burns 'sometimes,' 'easily,' or 'always,' and correct definition of sun protection factor. Application of a multivariate model yielded a sensitivity of 96%, specificity of 36%, and positive predictive value of sunscreen use of 89%.

Conclusions: Sunscreen use in parents is predictive of use in their children and relates more to experience with sunburn than with concerns about future skin cancer risk.

Little P.; Keefe M.; White J.; Keeley D.
Dept. of Primary Care, Fac. Medicine, University of Southampton, Aldermoor Health Centre,Southampton SO16 5ST United Kingdom
British Medical Journal (United Kingdom) 1995, 310/6984 (912-916)

Objective - To validate self screening by patients of high mole counts, assess the within family association of sun protection behaviour and mole counts, and estimate prevalence of risk factors for melanoma .

Setting and subjects - Systematic sample of families from a single affluent general practice population in Wessex.

Design - Subjects completed a questionnaire about risk factors for melanoma and counted their moles. Subsequently a mole count was done by a general practitioner trained at dermatology clinics.

Main outcome measures - Validation of self counts by observer's count. Within family association of sun protection behaviour and mole counts; self reported risk factors.

Results - 199/237 subjects (84%) returned the questionnaire; 212/237 (89%) were examined. High counts by patients on the front of the trunk (> 7 moles of >= 2 mm) were reasonably sensitive (79%), predictive (75%), and specific (97%) of the observer's mole counts (kappa = 0.74), unlike arm or total body counts. Sun protection behaviour correlated between individuals and other family members (Spearman's coefficient r = 0.50, P < 0.01). in the past three months 15/114 adults (13.2%, 95% confidence interval 7.0% to 19.4%) reported any change in a mole and 6/114 (5.3%, 2.0% to 11.1%) 'major' changes; 6/109 adults (5.3%, 2.6% to 11.1%) had both high mole counts and freckling.

Conclusions - Asking patients to count trunk moles could be a feasible way of identifying patients at high risk of melanoma . Concentrating on reported major changes in moles should avoid considerable workload in general practice. The generalisability of these findings and the adverse effects, net benefit in earlier diagnosis and prevention, and workload implications of such self screening need further research.

Lambert W.C.; Kuo H.-R.; Lambert M.W.
Medical Science Building, UMD-New Jersey Medical School, 185 South Orange Avenue,Newark, NJ 07103-2714 United States
Dermatologic Clinics (United States) 1995, 13/1 (169-209)

Xeroderma pigmentosum is a rare, recessively transmitted disease associated with increased sensitivity to ultraviolet radiation in wavelengths found in sunlight, development of cancers in sun-exposed areas of the body in much larger numbers and much earlier in life than in normal individuals, and in some patients, neurologic deficiencies unrelated to sun exposure. Extensive cellular, biochemical, and molecular genetic studies in numerous laboratories have revealed that cells derived from patients with this disease have defective repair of ultraviolet-light-induced damage in cellular DNA, and that extensive genetic heterogeneity and numerous distinct genes are involved in the genetics of this disease and the etiopathogenesis of its changes. A number of these genes and gene products are now being, or have been, cloned, and their gene products characterized.

Jeanmougin M.
Unite de Photodermatologie, Hopital Saint Louis,75010 Paris France
Nouvelles Dermatologiques (France) 1994, 13/6 (415-422)

The photoprotection of children is an extremely acute public health concern. The prevention of cutaneous cancers necessarily requires a reduction of sun exposures and the promotion of photoprotection since infancy. Facts are that children are much more exposed to sun than adults, that the majority of cutaneous carcinomas are photo-induced, and that intense and intermittent sun exposures increase the risk of a melanoma . For these reasons, it is absolutely necessary to protect children, especially children with a light phototype who are likely to be exposed to intense sunlight and/or who display multiple melanocytary nevi. Appropriate covering clothes, a sensible use of sun products, and family education are the basis of an efficient photoprotection. External photoprotectors should ensure a lasting protection against UVB, of course, but also against UVA and possibly against infrared rays. Because of the possible occurrence of allergies or contact photoallergies caused by sunscreens in children, photoprotectors exclusively made up of ultra thin mineral screens should be prescribed. These sunscreens also have another advantage: they are biologically inert, photo-stable, and their action is strictly a surface one. Sunscreens are not made to increase the number of hours one can spend under the sun, but to protect those cutaneous areas which cannot be covered with regular clothes. Family education and preventive information should be given by the mass media on the one hand and by physicians, pharmacists and educators on the other hand.

Schmitt G.J.
Korperpflegemittelbereich, Procter and Gamble Europa, Sulzbacher Str. 40,D-65824 Schwalbach/Taunus Germany
Dermatosen in Beruf und Umwelt (Germany) 1994, 42/3 (107-110)

There is increasing scientific knowledge concerning the risks for skin associated with chronic cumulative UV-irradiation extending from photoaging to non-melanoma carcinoma. Therefore, it is an important task for dermatologists to increase the public awareness for the necessity of adequate light protection preventing the harmful effects of UV irradiation at appropriate times throughout the year. Understanding the importance to protect against about 90% of the biologically relevant UV-B/UV-A irradation has to be promoted, especially among people with light sensitive skin. Such light portection effects are typically provided by products with a protection factor of then (DIN) or above. A balanced UV-B and UV-A screening is required.

Continued on the next page...

Hoffman S.; Yohn J.; Robinson W.; Norris D.
Colorado University Sch. of Medicine,Denver, CO United States
Hospital Practice (United States) 1994, 29/6 (37-40+43-44+47-48+50)

The disease is perhaps the clearest instance of a cancer for which early treatment is crucial. Increasing knowledge of risk factors (including brief, intense sun exposure and sunburn damage early in life) aids the identification of persons at highest risk-one reason for physicians not to be pessimistic about the value of urging patients to limit their sun exposure.

Becker B.; Jospe N.; Goldsmith L.A.
University of Rochester, Box 697, 601 Elmwood Avenue,Rochester, NY 14642 United States
Pediatric Dermatology (United States) 1994, 11/2 (120-124)

One morphologic feature of Turner syndrome is increased numbers of melanocytic nevi; however, little attention has been given to their characterization. The development of a melanoma in one of our patients with Turner syndrome prompted this study. We prospectively examined 10 patients with the disease, confirmed by karyotype. All patients underwent full body skin examination noting the number, size, distribution, and degree of clinical atypia of melanocytic nevi. Representative and unusual lesions were photographed. An average of 115 nevi were seen, with the majority measuring 1 to 5 mm. Most were located on the back and extremities. Clinical atypia was uncommon. Our patients had larger numbers of benign-appearing nevi than the general population. Large numbers of melanocytic nevi is a risk factor for melanoma , suggesting that these patients have an increase in one risk factor. Longitudinal studies are indicated to clarify this issue; nevertheless, we recommend periodic skin examinations and the regular use of sunscreens for individuals with Turner syndrome.

Setlow R.B.; Woodhead A.D.
Biology Department, Brookhaven National Laboratory,Upton, NY 11973 United States
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis (Netherlands) 1994, 307/1 (365-374)

The incidence of malignant cutaneous melanoma has been increasing for more than 50 years, and is now rising more rapidly than that of any other cancer. This increase is not explicable by changes in the physical environment, particularly by any observed increase in UVB radiation (290-320 nm). The distribution of melanomas on the body differs from the site distribution of nonmelanoma skin cancer (relatively many more melanomas occur on areas of the body not chronically exposed to sunlight, such as the back of the trunk in males, and the legs in females). This localization of melanoma , together with its epidemiology, suggest that a change in lifestyle has contributed to the fast-rising incidence in many countries. There is no convenient mammalian animal model for malignant melanoma . However, certain inter- and intra-specific hybrids of fish of the genus Xiphophorus are very sensitive to light-induced melanomas; we have used them to determine the wavelengths effective in melanoma induction. The action spectrum has a relatively very large component in the UVA region (320-400 nm) compared to human erythema. Hence, if the human and fish spectra were similar, the use of sunscreens that minimize erythema would have little effect in preventing the induction of melanoma , and if people using sunscreens expose themselves to sunlight for longer periods, they will be increasing dramatically their exposure to these melanoma -inducing wavelengths. Such considerations are sufficient to explain the rising incidence of malignant melanoma and its distribution on the body.

Halpern A.C.; Schuchter L.M.; Elder D.E.; Guerry IV D.; Elenitsas R.; Trock B.; Matozzo I.
Department of Dermatology, 3600 Spruce St,Philadelphia, PA 19104 United States
Journal of Clinical Oncology (United States) 1994, 12/5 (1028-1035)

Purpose: As potential precursors of melanoma and markers of increased melanoma risk, dysplastic nevi are suitable targets of strategies for melanoma chemoprevention. We report the results of a pilot study of topical retinoic acid in patients with dysplastic nevi.

Patients and Methods: Five male patients with dysplastic nevi applied tretinoin to half of the back for 6 months. Baseline photographs of dysplastic nevi were compared with posttreatment photographs and assessed for morphologic change. At study completion, each subject had four nevi excised from the treated side and four from the untreated side of the back. Biopsies were histologically evaluated for the presence of dysplasia.

Results: All patients developed signs of irritation as a result of treatment. One patient was not compliant with treatment due to skin irritation. The four compliant patients showed significant decreases in the clinical atypia of treated lesions, with concomitant fading and even disappearance of many treated nevi. Histologically, only four of 16 treated nevi met histologic criteria for dysplasia, in comparison to 13 of 16 untreated nevi.

Conclusion: These results suggest that there is concomitant clinical and histologic improvement in a significant percentage of dysplastic nevi treated with topical tretinoin. However, the utility of topical tretinoin for chemoprevention of melanoma is limited by difficulty of application and associated inflammation. While new strategies in chemoprevention of melanoma are explored, sun protection and assiduous avoidance of sunburn must remain the mainstay of melanoma prevention.

Urbach F.
Temple Medical Practices,Fort Washington, PA 19034 United States
Aktuelle Dermatologie (Germany) 1993, 19/12 (368-371)

Direct evidence for induction of non-melanoma skin cancer by UV irradiation is derived from animal experiments in mice and rats. A multitude of epidemiological data confirm this relationship also for human skin. Tumours are confined to skin sites with high cumulative sun exposure. Patients well-protected by constitutively dark skin pigmentation have a very low incidence of skin cancer. If natural defensive mechanisms are disturbed as in albinism or xeroderma pigmentosum, the risk of skin cancer is extremely high. In some countries a direct relationship between latitude and skin cancer with rising incidence in areas with high sun exposure has been described. Immunosuppression enhances tumourigenesis. A reduction of the stratospheric ozone layer by 1% may result in a 3% increase of squamous cell carcinoma incidence. Efforts to reduce air pollution in the troposphere increase UV irradiance at the earth's surface. Patients at risk should be encouraged to protect their skin by suitable clothing, use of sunscreens, and change of life styles, especially sun exposure habits during leisure time.

Grob J.J.; Guglielmina C.; Gouvernet J.; Zarour H.; Noe C.; Bonerandi J.J.
Service de Dermatologie, Hopital Ste-Marguerite, 270 Boulevard Ste-Marguerite,F-13274 Marseille Cedex 9 France
Dermatology (Switzerland) 1993, 186/2 (94-98)

Excessive sun exposure in the first 15 years of life has been shown to be a deter rninant risk factor for melanoma . This study was conducted on a randomly selected sample of 200 adolescents (13-14 years old) and 150 children (3 years old) in Marseille (South of France). Children and adolescents were examined and interviewed (mothers answered for young children). Our results show that a large number of highly sensitive children were not identified as such by their parents and most adolescents do not realize or at least admit being highly sun sensitive. Adequate sun protection measures were used in only 63% of 3-year-olds and 38% of adolescents. With reference to their constitutional skin sensitivity and taking into account their possible use of effective sun protection measures, 33% of the children and 62% of the adolescents were highly overexposed. Only good sun protection habits of the mother were predictive of acceptable sun exposure in children. In the adolescents the predictive variables were sun protection habits of the father and sunbathing only to obtain a tan. The main reason why adolescents sunbathed was embellishment. Conversely, most mothers said that they exposed their young children to the sun for health. Many adolescents and mothers were reasonably well informed but considered the risk of sun exposure to be exaggerated by the media. These results may be important to determine the targets of future melanoma prevention campaigns.

Webb G.
Div of Workplace Health and Safety, PO Box 6665,Cairns, QLD 4870 Australia
Journal of Occupational Health and Safety - Australia and New Zealand (Australia) 1992, 8/6 (479-485)

Ultraviolet radiation in sunlight presents a potential risk to health for outdoor workers. The paper examines the issues of health effects of solar radiation, including skin cancer, identification of high-risk groups for skin cancer, legal implications for employers in the context of occupational health and safety legislation, and measures for prevention or minimisation of solar radiation exposure of outdoor workers. The issue of worker compliance with protective measures is explored, using the Health Belief Model as a framework.

Calhoun K.H.; Wagner R.F.
Department of Otolaryngology, University of Texas Medical Branch, Galveston, TX 77550 United States
Texas Medicine (United States) 1991, 87/12 (64-69)

Skin cancer incidence is increasing rapidly. We outline the indications for and advantages of diagnostic techniques and treatments, including curettage and electrodesiccation, surgical excision, Mohs' micrographic surgery, cryosurgery, radiation therapy, interferon injection, and photodynamic therapy. We describe our interdisciplinary treatment protocol for skin cancer treatment and emphasize avoidance of the sun and early treatment of photodamaged skin. This treatment includes oral retinoids, topical tretinoin (Retin-A), 5 fluorouracil, and chemical peels performed with trichloroacetic acid or phenol.

Bolognia J.L.; Berwick M.; Fine J.A.; Simpson P.; Jasmin M.
Department of Dermatology, Yale University, School of Medicine, 333 Cedar St,New Haven, CT 06510 United States
American Journal of Diseases of Children (United States) 1991, 145/10 (1125-1129)

We investigated the effect of education on the sun exposure of newborns. Mothers of healthy newborns (n = 275) were enrolled in the spring of 1989 and interviewed by telephone in the fall of 1989. The mothers were divided into a control group, a low-level intervention group, and a high-level intervention group. Both the low-level and high-level interventions succeeded in reducing the amount of time the newborns were allowed to spend in direct sunlight. Both types of intervention also resulted in reduced sun exposure time for the mothers. Although the number of mothers who used sunscreen was approximately the same in all three groups, when sunscreen use was controlled for, the intervention groups spent significantly less unprotected time in the sun than the control group. The mothers and newborns in both intervention groups simply spent less time outdoors.

Beitner H.; Norell S.E.; Ringborg U.; Wennersten G.; Mattson B.
Department of Dermatology, Karolinska Hospital,S-104 01 Stockholm Sweden
British Journal of Dermatology (United Kingdom) 1990, 122/1 (43-51)

A case-control study of cutaneous malignant melanoma (CMM) was based on 523 incident cases and 505 age- and sex-matched controls selected from the general population. The purpose was to investigate the relative risk of developing CMM associated with different sun habits and indicators of pigmentation, such as skin type, eye colour and hair colour. Compared to people with black hair, blonde subjects had a relative risk of 74.4 (95% confidence interval, 45.8-120.8). Associations with skin type and eye colour were considerably weaker. Relative risks of about 1.5-2.5 were found for certain sun habits. The results suggest that in a population of Caucasian origin with a predominantly fair complexion, pigmentary status characterized by hair colour is a far more important aetiological factor than sun habits.

Pathak M.A.
Dept. Dermatol., Harvard Med. Sch., Massachusetts Gen. Hosp., Boston, MA 02114 United States
Journal of the American Academy of Dermatology (United States) 1982, 7/3 (285-314)

This review deals with topical and systemic approaches for protection of human skin against the harmful effects of solar radiation. Two concerns about the deleterious effects of sun exposure involve: (1) acute effects (e.g., sunburn and drug-induced phototoxicity) and (2) potential long-term risks of repeated sun exposures leading to development of solar elastosis, keratoses, induction of both nonmelanoma and melanoma skin cancer, and alteration of immune responses and functions. Action spectra of normal and abnormal reactions of human skin to acute and chronic effects of solar radiation are presented with a view to helping the physician prescribe the appropriate sunscreens. Factors that influence acute effects of sunburn are reviewed. Various artificial methods effective in minimizing or preventing harmful effects of solar radiation, both in normal individuals and in patients with photosensitivity-related problems, are discussed. Emphasis is placed on the commercially available chemical sunscreens and their properties. Sun protection factor (SPF) values of several brand-name formulations determined with a solar simulator under indoor conditions (laboratory) and with solar radiation under natural, field conditions are prevented. Factors responsible for variations of SPF values observed under indoor and outdoor conditions are reviewed. Systemic photoprotective agents and their limitations are outlined. The photobiology of melanin pigmentation (the tanning reaction) is briefly discussed, with emphasis on the dangers of using quick-tanning lotions for stimulation of the tanning reaction.

Chen W; Barthelman M; Martinez J; Alberts D; Gensler HL
Department of Radiation Oncology, College of Medicine, University of Arizona, Tucson 85724, USA.
Nutr Cancer (United States) 1997, 29 (3) p205-11

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis.

Bestak R; Halliday GM
Department of Medicine (Dermatology), University of Sydney, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Photochem Photobiol (United States) Jul 1996, 64 (1) p188-93

Previously we reported that the broad-spectrum sunscreen microfine titanium dioxide (MTD) could completely protect C3H/HeJ mice from UV radiation-induced immunosuppression to a contact sensitizer. In contrast, 2-ethylhexyl p-methoxycinnamate (2-EHMC), a UVB-absorbing sunscreen , only partially protected the skin immune system. In this study we investigated further this differential protection of the skin immune system by comparing the ability of 2-EHMC and MTD to protect these mice from the promotion phase of tumorigenesis. The mice were initiated using a single subcarcinogenic dose of 7,12-dimethylbenz(alpha)anthracene (DMBA) followed by promotion with chronic low-dose solar-simulated UV radiation for 32 weeks. We used doses of UV insufficient to cause edema in order to simulate daily human exposure to solar UV radiation. Mice were observed for the appearance of squamous cell carcinomas for 48 weeks. The DMBA-initiation alone and DMBA-initiated, sunscreen -treated groups did not develop tumors. Ultra-violet alone induced the appearance of tumors in 46% of mice at week 48 and therefore some tumors were initiated by UV. Initiation with DMBA prior to UV irradiation enhanced tumorigenesis such that 87% of mice at week 48 had tumors. Both 2-EHMC and MTD completely protected these mice from UV-induced promotion as well as from complete carcinogenesis despite the different UV-absorption spectra of the sunscreens and their differential abilities to protect from UV-induced immuno-suppression. Furthermore, we have shown that, if UV exposure is not increased to compensate for tolerance to edema, protection from tumorigenesis is afforded by sunscreens.

Robert C; Muel B; Benoit A; Dubertret L; Sarasin A; Stary A
Laboratory of Molecular Genetics, Institut de Recherches sur le Cancer, Villejuif, France.
J Invest Dermatol (United States) Apr 1996, 106 (4) p721-8

Although it is known that sunlight is carcinogenic,few molecular data are available concerning the mutagenic effects of ultraviolet (UV) B (290-320 nm) and UVA (320-400 nm) radiation in human cells. To analyze the biologic effects of UVA and UVB, we irradiated the 293 human cell line, derived from adenovirus-transformed human embryonic kidney cells, in which we had stably introduced a shuttle vector harboring the lacZ' bacterial gene as the mutagenesis target. Identical cell survival occurred after UVA doses 700-fold higher than UVB. This comparable to the UVA/UVB ratio that reaches the basal cell layer of the skin after sunlight exposure with UVB sunscreen . The frequency of UVA- and UVB- induced mutations increased with the UV dose as cell survival decreased. At cell survival levels greater than 10%, UVA and UVB induced similar frequencies of mutations in the episomal lacZ gene, whereas for cell survival lower than 10%, UVA induced twice as many mutations as UVB. Sequence analysis of 81 independent lacZ mutants (36 UVA- and 45 UVB-induced) revealed specific characteristics for some UV-induced-mutations, particularly for UVB. Mutations at A/T base pairs were induced more frequently by UVA than by UVB. The UVA-induced mutation spectrum that we have observed in human cells may help help to elucidate the mechanism of skin carcinogenesis.

Harth Y; Ulman Y; Peled I; Friedman-Birnbaum R
Department of Dermatology, Rambam Medical Center, Haifa, Israel.
Photodermatol Photoimmunol Photomed (Denmark) Aug 1995, 11 (4) p140-2

Sixty-three patients (mean age 54 +/- 9 years) who were treated for a basal cell carcinoma (BCC) and 54 control subjects (mean age 51 +/- 11 years) filled out detailed questionnaires on their sun exposure and sun protection habits. Patients were given the questionnaires at least 1 year after their skin tumors had been excised. Differences between patients and controls in mean age, gender, Fitzpatrick's skin type and eye and hair color were statistically nonsignificant. The level of education was high in both patients and controls (mean of 13.4 +/- 3.1 school years). Differences in education were statistically nonsignificant. We found that both patients and controls were knowledgeable about the role of sunscreens in preventing skin tumors (79% and 83% respectively) and in preventing sun-induced aging (90% and 85% respectively). Significantly more patients used sunscreens regularly (64%) compared with controls (36%). Nevertheless, our data show no statistically significant differences between the sun exposure habits of the patients previously treated for BCC and controls. Moreover, we found that, although 82% of the patients declared that they tried to avoid sun, only 49% regularly wore hats or shirts with long sleeves in the summer (19%). Sixty-two percent of the patients used two or fewer bottles of sunscreens per year, which is inadequate for effective year-round sun protection. In addition, we found that many patients, as well as the controls, applied sunscreens only once a day (57% and 46% respectively), did not reapply after swimming (58%, 74% respectively), and did not use sunscreens in the winter (49%, 61%). Our data show that, although patients after BCC removal have a significantly higher sunscreen use compared with controls, the amount and methods of application are less than adequate. Moreover, other simpler methods to prevent photodamage, such as simple sun avoidance or the use of protective clothing, are often neglected.

Grodstein F; Speizer FE; Hunter DJ
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J Natl Cancer Inst (United States) Jul 19 1995, 87 (14) p1061-6

BACKGROUND: Few epidemiologic studies are available that quantify the magnitude of the risk of squamous cell carcinoma (SCC) of the skin associated with sun exposure and related factors such as skin type. In addition, several studies have found an association between cigarette smoking and SCC.

PURPOSE: We prospectively examined the risk of developing SCC in relation to phenotype and the effects of sun exposure, as well as to cigarette smoking and other factors, during 8 years of follow-up in a cohort of 107,900 predominantly white women aged 30-55 years at base line in 1976.

METHODS: Questionnaires regarding medical history and health-related variables were sent to Nurses' Health Study participants every 2 years, beginning in 1976. Information on constitutional factors (natural hair color, childhood and adolescent tendency to sunburn and tan, and lifetime number of severe sunburns), lifestyle factors (regular time spent outdoors in the summer and sunscreen use), the state lived in at birth and at ages 15 and 30 years, and cigarette smoking habits were ascertained by questionnaire. A total of 197 women with first-incident, histologically confirmed, invasive SCCs that were diagnosed from 1982 to 1990 were included in this analysis. Multivariate analysis using proportional hazards models was used to calculate the relative risks (RRs) and corresponding 95% confidence intervals (CIs), with adjustment for confounders.

RESULTS: The risk of SCC was increased in women living in California (RR = 1.8; 95% CI = 1.3-2.6) and Florida (RR = 2.1; 95% CI = 1.1-3.9) at base line, compared with those living in the northeastern states. This risk was higher for women living in those states at birth and at 15 years of age (RR = 2.5; 95% CI = 1.4-4.4 for California and RR = 3.0; 95% CI = 0.7-1.2 for Florida). Red (RR = 2.0; 95% CI = 1.1-3.7) and light brown (RR = 1.7; 95% CI = 1.2-2.4) hair colors were associated with an increased risk of SCC, compared with dark brown hair. After adjusting for the number of sunburns, women who tended to burn after 2 or more hours of sun exposure as children had a slightly higher risk of SCC than those who never burned (RR = 1.5; 95% CI = 0.9-2.5 for burn and RR = 1.1; 95% CI = 0.6-2.0 for painful burn), although the actual number of severe burns appeared to be a more important factor (RR = 2.4; 95% CI = 1.5-4.0 for six or more burns). Finally, current cigarette smokers showed a 50% increase in the risk of SCC compared with never smokers (RR = 1.5; 95% CI = 1.1-2.1).

CONCLUSION: Exposure to the sun leading to sunburn, particularly at early ages, should be avoided to decrease the risk of incident SCC.

Naylor MF; Boyd A; Smith DW; Cameron GS; Hubbard D; Neldner KH
Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City.
Arch Dermatol (United States) Feb 1995, 131 (2) p170-5

BACKGROUND AND DESIGN: A controlled trial was undertaken from December 1987 to December 1990 to test the hypothesis that a strong sunscreen can reduce the number of cancerous and precancerous skin lesions. Candidates were selected from a high-risk population attending either a university- or Veterans Affairs-based dermatology practice in Lubbock, Tex, for a prospective, double-blind, controlled trial of daily application of sunscreen vs placebo over a 2-year period. Participants were asked to volunteer if they had demonstrated premalignant changes (actinic keratoses) or nonmelanoma skin cancer (basal cell carcinoma or squamous cell carcinoma), had continuing sun exposure, and were not using sunscreen on a regular basis. Fifty-three volunteers were initially enrolled in the study, and 37 came for the final 24-month visit.

RESULTS: The rate of appearance of new precancerous skin lesions was less for the treatment group than for control subjects. People with darker skin had fewer actinic keratoses, women had fewer lesions than men, and people with fewer lesions at enrollment had fewer lesions during the study. The numbers of new nonmelanoma skin cancers appearing during the study period were too small for statistical analysis.

CONCLUSIONS: The regular use of sunscreens can significantly reduce cutaneous neoplasia, as indicated by its suppression of precancerous lesions. A longer and/or larger study would be necessary to demonstrate an effect on malignant lesions.

Green A; Battistutta D; Hart V; Leslie D; Marks G; Williams G; Gaffney P; Parsons P; Hirst L; Frost C; et al
Queensland Institute of Medical Research, Brisbane, Australia.
Control Clin Trials (United States) Dec 1994, 15 (6) p512-22

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial (the Nambour Trial) is a field trial conducted in an unselected adult population in Australia. Using a randomized 2 x 2 factorial design, the principal aim is to evaluate whether regular use of high-protection sunscreen and/or dietary supplementation with beta-carotene (30 mg daily) can alter the incidence rates of basal cell carcinomas and squamous cell carcinomas of the skin over a minimum follow-up time of 4.5 years. Changes in the incidence of solar keratoses and actinic eye disease and the rate of photoaging after intervention will also be investigated. In 1992, 1626 participants between the ages of 25 and 75 years were enrolled, all of whom had been randomly selected from residents of the southeastern Queensland township of Nambour for an earlier skin cancer prevalence survey. This paper describes the background to the trial and its design, with respect to evaluation of effects on actinic skin disease, and documents the baseline characteristics of participants recruited into the Nambour Trial.

Guercio-Hauer C; Macfarlane DF; Deleo VA
State University of New York Health Science Center at Brooklyn.
Am Fam Physician (United States) Aug 1994, 50 (2) p327-32, 334

Overexposure to ultraviolet and visible radiation causes sunburn. Aspirin and other nonsteroidal anti-inflammatory drugs, cool baths and topical steroids offer only mild relief. Long-term sun exposure causes chronic inflammatory skin changes. Photodamage, rather than the normal aging process, may account for 90 percent of age-associated cosmetic skin problems. Physicians should stress to their patients that all ultraviolet exposure (including sun beds and tanning salons) causes skin damage. Regular sunscreen use during childhood and adolescence may result in an 80 percent reduction in the lifetime incidence of ultraviolet-induced skin damage, including nonmelanoma skin cancers. (17 Refs.)

Thompson SC; Jolley D; Marks R
Anti-Cancer Council of Victoria, Carlton, Australia.
N Engl J Med (United States) Oct 14 1993, 329 (16) p1147-51

BACKGROUND. The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous - cell carcinoma of the skin.

METHODS. We conducted a randomized, controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer (September 1991 to March 1992). The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head, neck, forearms, and hands.

RESULTS. The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group (difference, 1.53; 95 percent confidence interval, 0.81 to 2.25). The sunscreen group had fewer new lesions (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71) and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80) than the base-cream group. There was a dose-response relation: the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones.

CONCLUSIONS. Regular use of sunscreens prevents the development of solar keratoses and, by implication, possibly reduces the risk of skin cancer in the long-term.

van Praag MC; Tseng LN; Mommaas AM; Boom BW; Vermeer BJ
Department of Dermatology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
Drug Saf (New Zealand) May 1993, 8 (5) p340-9

Psoralen photochemotherapy (PUVA) is a combination of orally administered psoralen and long wave ultraviolet-A radiation (UVA), and is one of the most effective forms of therapy for psoriasis. The unwanted effects of PUVA therapy can be divided into short and long term adverse effects. The short term adverse effects include erythema, pruritus, nausea and headache. While short term adverse effects are limited and reversible after discontinuation of treatment, potential long term adverse effects such as chronic actinic skin damage, dyskeratotic and precancerous skin conditions, nonmelanoma skin cancer, immunological alterations and cataract formation are of greater concern. Long term risks associated with PUVA therapy can be minimised by several measures. Careful patient selection is mandatory; for example, patients with chronic actinic damage and a history of skin cancer may bear a higher risk for the development of new cancers, and previous arsenic intake and ionising radiation also increase the risk of nonmelanoma skin cancers. Certain drug combinations make it possible to lower the UVA dose, which is important because of the dose-dependent increase in the incidence of squamous cell carcinomas in patients treated with PUVA. It has been demonstrated that 200 treatments or a total UVA dose of 1200 J/cm2 seems to be the threshold for development of nonmelanoma skin cancer. Shielding male genitalia during PUVA treatment is essential because of the increased risk of genital squamous cell carcinomas. Yearly dermatological examination to detect skin cancer at an early stage is highly advisable. Sunscreen use, protective clothing and avoidance of sun exposure reduce the uncontrolled dose of solar UV radiation. Other psoralens with a less carcinogenic potential can be used. UVA-opaque sunglasses during the entire period of increased photosensitivity after psoralen ingestion help avoid cataract formation. Assignment to PUVA ought to be based on the risk-benefit ratio for the individual patient and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians. (56 Refs.)

Reeve VE; Greenoak GE; Gallagher CH; Canfield PJ; Wilkinson FJ
Aust J Exp Biol Med Sci (Australia) Dec 1985, 63 (Pt 6) p655-65

The effect of two immunosuppressive agents, azathioprine and cyclophosphamide, with and without UVB sunscreen protection on UV-induced skin carcinogenesis was studied in the albino hairless mouse. In a daily treatment regime spanning 9 weeks, groups of mice were immunosuppressed with either drug, and were exposed to minimally erythemal doses of a light source simulating the UV portion of the solar spectrum. The accumulated UV exposure alone induced skin tumours in 77% of mice. Azathioprine, but not cyclophosphamide, significantly enhanced the incidence of UV tumorigenesis. Photoprotection by topical application of one of two commonly used UVB sunscreens, 2-ethyl-hexyl-p-methoxycinnamate (2-EHMC) or octyl-N-dimethyl-p -aminobenzoate (o-PABA), reduced the UV tumour incidence to zero in immunologically normal mice and to 8-15% in immunosuppressed mice. Unexpressed latent tumour initiations were revealed in all sunscreen -protected groups by the subsequent application of a tumour promoter, croton oil. In immunologically normal mice 2-EHMC had allowed initiations in 39% of UV-irradiated mice, and o-PABA in 16.5%. However, in UV-irradiated mice immunosuppressed with azathioprine there had been initiations in 78% of mice protected with 2-EHMC and 65% of mice protected with o-PABA. Photoprotected mice immunosuppressed with cyclophosphamide did not show the same increase in UV-initiations (22% with 2-EHMC, 23% with o-PABA). These results provide evidence that azathioprine increases the susceptibility of the skin to UV carcinogenesis. However, UVB sunscreens afford effective protection from overt tumour expression in the absence of a tumour promoter.

Lundeen RC; Langlais RP; Terezhalmy GT
J Am Dent Assoc (United States) Oct 1985, 111 (4) p617-21

It has been stated that the key to prevention of oral cancer is to avoid the "five Ss: smoking, spirits, spices, sepsis, and syphilis." There is certainly enough evidence to add another "S"--sunlight. Although there is a paucity of information in the dental literature on the use of sunscreens, the following dermatologic recommendation is noteworthy: "Persons with Skin Types I and II should never sunbathe and should adopt a program of daily application of effective sunscreens (SPF 15) as a habit and from an early age--in much the same manner as daily brushing of the teeth is adopted to prevent dental caries." The dentist should advise patients at high risk for squamous cell carcinoma and those with recurrent herpes labialis to use a sunscreen for the lips of at least SPF 15. The best sunscreen formulation at the present time is a combination of either PABA or an ester of PABA along with a benzophenone. A frequent combination seen on product labels is Padimate O and oxybenzone. Sunscreens should be used year-round on the lips with two applications 1 hour before sun exposure, and hourly reapplication while in the sun. If the convenience of a "lipstick" product is not important to the patient, then a skin product of the liquid or gel type should be used. If the appearance is not important, a white opaque cream containing titanium dioxide, talc, or zinc oxide may be used as a physical barrier. Women may use an opaque lipstick, but should first apply a chemical sunscreen of at least SPF 15.(ABSTRACT TRUNCATED AT 250 WORDS)

Cartwright LE; Walter JF
J Am Acad Dermatol (United States) Jun 1983, 8 (6) p830-6

Sunscreens containing 5-methoxypsoralen (5-MOP) are currently being marketed to promote tanning by inducing psoralen-mediated ultraviolet (UV) A (320-400 nm) melanogenesis. The rationale is that this may prevent UVB (290-320 nm) radiation-induced skin damage. However, mouse studies have shown that 5-MOP has the same cutaneous photocarcinogenic potential as 8-methoxypsoralen. In addition, the 5-MOP--containing sunscreen Sun System III (SS III), when combined with UVA, induces epidermal ornithine decarboxylase activity, an enzyme associated with tumor promotion. Therefore, we investigated whether SS III had sufficient psoralen concentration to be tumorigenic in hairless mice exposed to chronic, intermittent UVA radiation. SS III was applied to hairless mice 5 days per week for 20 weeks. After each application the mice were exposed to 2.5 to 10 joules/cm2 UVA radiation. All test groups developed atypical squamous papillomas in direct proportion to the dosage of UVA radiation received. A shorter latency period for tumor development was seen with larger UVA doses. Test animals followed up to 1 year developed invasive squamous cell tumors. Control groups (SS III without UVA and UVA without SS III) remained free of tumors. Animals receiving SS III plus UVA developed persistent skin thickening and increased dermal cyst formation similar to that reported with chronic exposure to UVB, a known carcinogenic wavelength. Over-the-counter sunscreens containing 5-MOP do contain sufficient psoralen concentrations to cause cutaneous phototoxicity and photocarcinogenicity in mice, and their use in humans should be discouraged in the interest of preventing further UV-induced skin damage and skin cancer.

Wulf HC; Poulsen T; Brodthagen H; Hou-Jensen K
J Am Acad Dermatol (United States) Aug 1982, 7 (2) p194-202

Sunscreens with different sun protection factors (SPFs) have been tested for their capability of delaying or preventing actinic damage and skin cancer development in groups of hairless, pigmented mice exposed to artificial ultraviolet (UV) light of increasing intensity. The dose delivered was less than or equal to 1 minimal erythema dose (MED) in the group of untreated mice, so that the mice to which sunscreens were applied never obtained a sunburn after UV exposure. The quality of UV light was similar to bright midday sun at a latitude of 56 degrees (city of Copenhagen). Tumorigenesis was demonstrated to be delayed corresponding to the SPF claimed by the manufacturer, but almost all of the UV-irradiated mice developed skin tumors. Histologic examination revealed actinic degeneration and tumors of squamous cell type with marked variation in differentiation. Metastases to lymph nodes and lungs were found in only 10%. Toxic reactions, such as eczematous-like skin reactions, dark coloring, and amyloidosis, were observed predominantly in the group treated with the sunscreen of highest SPF value. Long-term investigations seem to be necessary to unveil these problems--in particular, the specific SPF value, in sunscreens, that should be recommended to the public for prevention or delay of actinic damage and/or cancer development.

Soparkar C.N.S.; Patrinely J.R.
Dr. C.N.S. Soparkar, Plastic Eye Surgery Associates, PLLC, 6500 Fannin Street, Houston, TX 77030 United States
Current Opinion in Ophthalmology (United States) 1998, 9/5 (49-53)

Eyelid cancers, like most malignancies, are on the rise, creating an ever-enlarging population of patients with these diseases. Trends in eyelid cancer diagnosis, prognostic evaluation, prevention, and management are reviewed. Special emphasis is placed upon understanding perineural invasion by squamous cell carcinoma, the role of genetic mutations in eyelid cancer development and prognosis, and new techniques for total upper eyelid reconstruction.

English III J.C.; Canchola D.R.; Finley E.M.
Dr. J.C. English III, 1940 Avalon Ct., Colorado Springs, CO 80919 United States
American Family Physician (United States) 15 APR 1998 , 57/8 (1860-1864)

Basal cell carcinoma is the most common skin malignancy. While this lesion most often occurs in sun-exposed areas of the skin, it can also develop in sites that are not usually exposed to sunlight or artificial ultraviolet radiation, such as the breast, palm or groin. A periodic complete examination of the skin should be performed to ensure that atypical presentations of basal cell carcinoma are not overlooked or misdiagnosed. Treatment options include curettage and desiccation, cryosurgery, surgical excision, radiotherapy and Mohs micrographic surgery.

Burpen R.; Scaletta C.; Frenk E.; Panizzon R.G.; Applegate L.A.
L.A. Applegate, Department of Dermatology, Laboratory of Photobiology, University Hospital, CH-1011 Lausanne Switzerland
Lee.Laurent-Applegate@chuv.hospvd.ch
International Journal of Cancer (United States) 13 APR 1998, 76/2 (201-206)

DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p33 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230 +/- 15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5 +/- 28.5 and 103 +/- 15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.

Witheiler D.D.; Lawrence N.; Cox S.E.; Cruz C.; Cockerell C.J.; Freemen R.G.; Brody H.J.
Dr. D.D. Witheiler, 221 W. Colorado Blvd., Dallas, TX 75208 United States
Dermatologic Surgery (United States) 1997, 23/3 (191-196)

BACKGROUND. Few studies have examined the long-term efficacy of fluorouracil (FU) or chemical peels for the treatment of actinic keratoses (AK). Our earlier work examined the efficacy and safety of a medium-depth chemical peel compared with the standard regimen of topical FU in the treatment of widespread facial AK through 12 months.

OBJECTIVES. To determine long-term efficacy of both treatments by extending our observations through 32 months.

METHODS. Fifteen patients with severe facial actinic damage were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% FU cream for 3 weeks. Parameters evaluated at 1, 6, 12, and 32 months included counts of visible AK, random skin biopsies from both treatment areas, development of intercurrent neoplasms, and surveys assessing sun exposure.

RESULTS. Eight patients were available for reevaluation at 32 months. Both treatment sides showed a reduction in mean number of AK at 12 months followed by an increase in mean AK number between 12 and 32 months. Improvements in biopsies of clinically actinically damaged skin were seen in keratinocytic atypia, hyperkeratosis, parakeratosis, and inflammation at all treatment times during the study with both treatments. Three squamous cell carcinomas developed in the patients after initial treatment; one developed on the side treated with the peel, and two developed on the side treated with fluorouracil. Surveys failed to demonstrate an association between sun exposure and clinical response.

CONCLUSION. Based on these findings, patients with widespread actinic keratoses treated with medium-depth chemical peel or with 5% FU should be reevaluated yearly or every 1.5 years for reappearance of AK and retreatment.

Kibarian M.A.; Hruza G.J.
One Barnes Hospital Plaza,St Louis, MO 63110 United States
Postgraduate Medicine (United States) 1995, 98/6 (39-40+45-46+48+55-56+58)

The incidence of nonmelanoma skin cancer is rapidly increasing. With early diagnosis and treatment, almost all basal cell and squamous cell carcinomas can be cured. Premalignant actinic keratoses are treated with cryosurgery; the COinf 2 laser is the treatment of choice for actinic cheilitis. Generally; nonmelanoma skin cancer can be effectively treated with excision, electrodesiccation and curettage, cryosurgery, or radiation therapy; 5-year cure rates are over 90%. Large, locally recurrent, and aggressive lesions, as well as lesions located in the central face, are best managed with Mohs' surgery; 5-year cure rates as high as 99% have been reported. Patient education about the dangers of sun exposure and tanning salons can potentially reduce the incidence of nonmelanoma skin cancer. The use of sunscreens starting early in life should be stressed.

Hacker S.M.; Browder J.F.; Ramos-Caro F.A.
Dermatology/Cutaneous Surgery Div., Department of Medicine, Florida University Coll. of Medicine, PO Box 100277,Gainesville, FL 32610-0277 United States
Postgraduate Medicine (United States) 1993, 93/8 (101-111)

Basal cell carcinoma is the most common type of malignant tumor in the United States. The five types of basal cell carcinoma (noduloulcerative, pigmented, morpheaform, and superficial basal cell carcinoma, and premalignant fibroepithelioma) vary in clinical presentation and behavior. Diagnosis is made by skin biopsy. The size, type, and site of a lesion and the age and sex of the patient affect the choice of treatment. Electrodesiccation and curettage, cryosurgery, surgical excision, Mohs' surgery, and radiation therapy are available. Knowledge of these therapies and of when they should and should not be used is important in proper management of basal cell carcinoma.

Shelley E.D.; Shelley W.B.
Department of Medicine, Medical College of Ohio, PO Box 10008,Toledo, OH 43699-0008 United States
Cutis (United States) 1992, 50/3 (217-220)

Most of what we learn comes from reading, not from listening. Thus, for us, the poster presentation is ideal. It allows us to escape from the confinement of the lecture hall and from the constraint of having to listen to the obvious, the repetitious, the uninteresting, and the irrelevant. Come with us and scan those posters that caught our roving clinical eye as we viewed a thousand poster 'lectures.'

Prawer S.E.
Assoc. Skin Care Specialists, 7205 University Ave NE,Fridley, MN 55432-3133 United States
Postgraduate Medicine (United States) 1991, 89/8 (51-54+59-61+64-66)

Severe photoaging of the skin, which may be caused by exposure to both natural and artificial ultraviolet light, ultimately results in actinic keratoses and cancer. Cancers are common on the head, neck, arms, and hands. Because of the potential for metastasis, squamous cell carcinomas generally require surgical excision and histologic examination. Although metastasis is rare with basal cell carcinoma, neglected lesions around the eyes, nose, or ears can invade bone, nerves, and cartilage and may cause death. Avoidance of sun, physical protection, and regular use of sunscreens are recommended.

Flindt-Hansen H.; Thune P.; Nielsen C.J.
Department of Dermatology, Ullevaal Hospital, N-0407 Oslo 4 Norway
Photodermatology (Denmark) 1989, 6/6 (263-267)

A solution of para-aminobenzoic acid (PABA) was exposed to ultraviolet (UV) radiation emitted from a Philips TL 40 W/12 sunlamp and the degree of photodegradation following an exposure of 27 J/cmsup 2 was estimated to be approximately 40%. The formation of the photoproducts was confirmed by mass spectroscopy and UV spectroscopy. The solution was painted on the backs of hairless light-pigmented mice prior to daily UV irradiation by the above sunlamp, and this procedure was continued for 30 weeks. The preirradiated solution of PABA significantly retarded the tumor induction time and reduced significantly the number of squamous cell carcinomas compared with non-protected controls. This tumor-retarding ability did not differ significantly from the effect achieved then using nonirradiated PABA.

Kozarev J
Med Pregl (Yugoslavia) Nov-Dec 1998, 51 (11-12) p555-8

OBJECTIVE: There is evidence that in spite of worldwide campaigns against excessive sun exposure, children as well as adults still spend long periods in the sun. The purpose of this study was to evaluate sun exposure in a group of doctors of different specialties and to compare their knowledge about sun protection methods with regular use of sun protection products.

METHODS: 51 doctors of different specialties, volunteers, mean age 40.78, filled out questionnaires with 21 multiple choice questions about their skin type, sun exposure habits, sun protection habits and questions about meaning of the Sun Protection Factor.

RESULTS: Thirty-three percent of our study participants spent more than two peak ultraviolet hours outdoors every day, and additional 33.33% are sun exposed for longer than 5 hours, regularly. Only 39% of them utilized sunscreens. Majority of sunscreen users utilized less than 100 ml of commercial sunscreen products which is an inadequate amount for full body protection per year. Majority of study participants did not believe that sunscreens could prevent skin cancer, but 57% of them believed that these compounds can slow the process of skin aging . Meaning of the term Sun Protection Factor is not familiar to 84.3% study participants. The two most common reasons for not using sunscreens are time consuming application and high cost.

CONCLUSION: Results of the presented study confirm our statement that there is bad understanding of a need for sun protection which is in correlation with deficient application of sun protective measures. It should be stressed out that our study participants lack well formed sun protection habits.

Gasparro FP; Mitchnick M; Nash JF
Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
francis.gasparro@mail.tju.edu
Photochem Photobiol (United States) Sep 1998, 68 (3) p243-56

The use of sunscreen products has been advocated by many health care practitioners as a means to reduce skin damage produced by ultraviolet radiation (UVR) from sunlight. There is a need to better understand the efficacy and safety of sunscreen products given this ongoing campaign encouraging their use. The approach used to establish sunscreen efficacy, sun protection factor (SPF), is a useful assessment of primarily UVB (290-320 nm) filters. The SPF test, however, does not adequately assess the complete photoprotective profile of sunscreens specifically against long wavelength UVAI (340-400 nm). Moreover, to date, there is no singular, agreed upon method for evaluating UVA efficacy despite the immediate and seemingly urgent consumer need to develop sunscreen products that provide broad-spectrum UVB and UVA photoprotection. With regard to the safety of UVB and UVA filters, the current list of commonly used organic and inorganic sunscreens has favorable toxicological profiles based on acute, subchronic and chronic animal or human studies. Further, in most studies, sunscreens have been shown to prevent the damaging effects of UVR exposure. Thus, based on this review of currently available data, it is concluded that sunscreen ingredients or products do not pose a human health concern. Further, the regular use of appropriate broad-spectrum sunscreen products could have a significant and favorable impact on public health as part of an overall strategy to reduce UVR exposure. (147 Refs.)

Continued on the next page...

Takeuchi T; Uitto J; Bernstein EF
Department of Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Invest Dermatol (United States) Apr 1998, 110 (4) p343-7

Increasing evidence demonstrates that ultraviolet A radiation (UVA) contributes to photoaging, which results in the accumulation of massive amounts of abnormal elastic material in the dermis of photoaged skin. To study UVA-induced photoaging in an in vivo system, we utilized a line of transgenic mice containing the human elastin promoter linked to a chloramphenicol acetyl transferase reporter gene. Our prior work demonstrates promoter activation in response to ultraviolet B radiation (UVB), UVA, and psoralen plus ultraviolet A radiation in the skin of these mice. The addition of psoralen (8-MOP) prior to administration of UVA results in substantial increases in promoter activation, as compared with UVA alone. To demonstrate the utility of these mice as a model of UVA-induced photodamage, we administered four lotions to the skin of our transgenic mice that included: a sunscreen containing octyl methoxycinnamate and benzophenone-3 with a sun protection factor (SPF) of 15, the UVA filter butyl methoxydibenzoylmethane, the SPF 15 sunscreen and the UVA filter together, and the lotion vehicle alone. Following sunscreen administration, mice received a single psoralen plus ultraviolet A radiation treatment. All sunscreens decreased chloramphenicol acetyl transferase activity with the SPF 15 sunscreen , the UVA filter, and the combination SPF 15 sunscreen and UVA filter, resulting in increasing degrees of protection against psoralen plus ultraviolet A radiation. These results demonstrate that this model functions as a rapid and sensitive model of UVA photodamage for the identification and comparison of compounds that protect against UVA-induced photoaging.

Fulton JE Jr
Dermatol Surg (United States) Jan 1998, 24 (1) p91-9

BACKGROUND: Modern skin resurfacing began with wire brush surgery. The short-pulse carbon dioxide (CO2) lasers provide an alternative approach for facial rejuvenation. However, the potential for the same complications exist.

OBJECTIVES: To review the more common complications, the reasons for their development, and their possible avoidance.

METHODS: After pre-op evaluation and skin conditioning, a protocol for resurfacing was followed with standardized settings on the Ultrapulse CO2 laser. On the glabrous skin 300 mJ of energy and 60 W of power were used. On the eyelid skin the settings were reduced to 250 mJ and 50 W. After three passes with the Computer Pattern Generator (CPG), a semi-occlusive dressing was applied for the first 5 days after surgery. Then, a bland petrolatum ointment was applied for an additional 5 days. Finally, a moisturizer with sunscreen or a bleaching cream was used.

RESULTS: It was possible at these energy fluences to avoid excessive collagen denaturation and to facilitate wound healing with occlusive dressing. However, complications still occurred. Examples of these are presented in detail.

CONCLUSION: Complications can be minimized with patient education, using optimal laser settings, applying occlusive dressings, and recognizing pending problems early.

Darr D; Dunston S; Faust H; Pinnell S
North Carolina Biotechnology Center, Raleigh, N.C., USA.
Acta Derm Venereol (Norway) Jul 1996, 76 (4) p264-8

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen . A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.

Bissett DL; McBride JF
Miami Valley Laboratories, Procter & Gamble Company, Cincinnati, OH 45253-8707, USA.
J Am Acad Dermatol (United States) Oct 1996, 35 (4) p546-9

BACKGROUND: Iron is a factor in skin photodamage, apparently by way of its participation in oxygen radical production. Certain topical iron chelators are photoprotective.

OBJECTIVE: Our purpose was to determine the level of topical photoprotection provided by the iron chelator 2-furildioxime (FDO) in combination with sunscreen in short- and long-term photoprotection models.

METHODS: Guinea pigs were treated topically with FDO, sunscreen , and a combination of the two and were then exposed to varying doses of UV radiation to determine the sun protection factor (SPF). Hairless mice were treated topically with FDO, sunscreen , and a combination of the two and then subjected to long-term exposure to a suberythemal dose of UV radiation. The mice were evaluated for skin wrinkling and skin tumors.

RESULTS: In guinea pigs, topical FDO combined with sunscreen provided more than additive protection; 5% FDO alone provides approximately SPF 4, whereas 5% FDO combined with an SPF 4 sunscreen product yielded an SPF of more than 30. In hairless mice exposed long term to UV radiation, 5% FDO and sunscreen delayed tumor onset by a mean of 8 and 12 weeks, respectively. The combination of FDO and sunscreen delayed tumor onset by a mean of 58 weeks. A similar more than additive level of protection was observed for skin wrinkling.

CONCLUSION: Topical FDO combined with sunscreen is a potent photoprotection system against both short- and long-term UV radiation exposure.

Gilchrest BA
Department of Dermatology, Boston University School of Medicine, MA 02118, USA.
Br J Dermatol (England) Dec 1996, 135 (6) p867-75

Intrinsic (chronological) skin ageing is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage), on the intrinsic ageing process results, at least initially, in a hypertrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis: massive elastosis (deposition of abnormal elastic fibres), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown to partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova, Renova), developed specifically for the treatment of photodamaged skin, has been extensively investigated in multicentre, double-blind trials and has been shown to produce significant improvement within 4-6 months of daily use, compared with vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compounds have been reported to normalize hyperkeratinization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that affect the skin and has demonstrated that many of the unwanted changes can be improved by topical therapy. (50 Refs.)

Taylor CR; Sober AJ
Department of Dermatology, Harvard University, Massachusetts General Hospital, Boston 02114, USA.
Annu Rev Med (United States) 1996, 47 p181-91

Sunlight exposure produces a variety of adverse cutaneous effects. Erythema, photosensitivity, and immunologic alterations represent acute events, whereas photoaging and carcinogenesis are long-term consequences. These adverse cutaneous sequelae can be minimized by photoprotection in the form of sun avoidance, regular cover-up with clothing, and sunscreen application. This chapter reviews the diagnosis and treatment of sun-related skin disorders and recommendations for reducing photodamage. (40 Refs.)

Kaminester LH
Department of Dermatology and Cutaneous Surger, University of Miami (Fla), USA.
Arch Fam Med (United States) May 1996, 5 (5) p289-95

Photoprotection encompasses all methods to prevent UV radiation (UVR) damage to the skin, including sunscreens, clothing, seeking shade, and duration and time of the day spent outdoors under UVR. As scientific research validates short- and long-term detrimental effects of UVR, physicians and the public must become increasingly aware of these problems to avoid them. Photoaging is defined. Choice of sunscreens, their Food and Drug Administration labeling, and future sunscreen products are reviewed. Hazards of UVR on the skin include acute sunburn, photocarcinogenesis, immunologic suppression, and photoaging. Distinguishing between UV-A and UV-B damage to the skin is discussed. Education of physicians and their patients is crucial to reduce future photodamage to our population, especially with a reduction of the ozone layer and with patients having more free time. The complete skin examination is emphasized as a method to detect photodamaged skin and give patients insight to provide themselves with future photoprotection. A summary of advice for patients is provided for physicians to give to their patients. (135 Refs.)

Boyd AS; Naylor M; Cameron GS; Pearse AD; Gaskell SA; Neldner KH
Department of Medicine, Vanderbilt University, Nashville, TN 37232-5227, USA.
J Am Acad Dermatol (United States) Dec 1995, 33 (6) p941-6

BACKGROUND: Sunscreen application to the skin of hairless mice is effective in reversing the histologic changes associated with photoaging (solar elastosis, epidermal thickening, collagen depletion, glycosaminoglycan deposition). These reparative processes have not been studied in human beings.

OBJECTIVE: The aim of this study was to evaluate histologically the effects of daily application of a UVA/UVB sunscreen versus placebo.

METHODS: We examined 46 patients who were given either sunscreen or vehicle and asked to apply it daily for 24 months. Punch biopsy specimens were obtained from preauricular skin at 0, 12, and 24 months. Each specimen was examined for epidermal thickening and organization and dermal inflammatory infiltrate by light microscopy. Computer-generated analysis of tissue sections was used to evaluate solar elastosis.

RESULTS: A significant difference in solar elastosis was found between the treatment groups; however, the other features remained largely unchanged.

CONCLUSION: The dermal changes of photoaging may be affected differently than epidermal changes when UV radiation exposure is diminished. UVA and UVB may contribute diversely to these cutaneous changes. Computer-generated evaluation of dermatoheliosis may be more accurate than visual inspection.

Creidi P; Faivre B; Agache P; Richard E; Haudiquet V; Sauvanet JP
Service de Dermatologie I, Centre Hospitalier et Universitaire, Hopital Saint-Jacques, Besancon, France.
Maturitas (Ireland) Oct 1994, 19 (3) p211-23

The effects of Premarin cream on ageing facial skin were studied in a randomised, double-blind, parallel group study. Fifty-four women aged 52-70 years who had moderate to severe facial cutaneous ageing, applied 1 g of either Premarin cream (0.625 mg conjugated oestrogens per gram of cream), or placebo cream (same composition with the exclusion of conjugated oestrogens) to the face nightly for 24 weeks. Each morning these women protected their face with a sunblock SPF 15. Skin thickness was measured by B-scan ultrasonic echography, and skin microrelief by profilometry. Each subject's facial appearance was also evaluated by the subject herself and by the clinician. A statistically significant difference (P = 0.013) in favour of Premarin cream was detected in skin thickness at week 24. Skin thickness (dermal plus epidermal) for the women who used Premarin cream increased from 1.56 +/- 0.20 mm at baseline to 1.68 +/- 0.19 mm, compared with 1.52 +/- 0.20 mm at baseline to 1.59 +/- 0.19 mm in the placebo group. Premarin cream was also significantly more effective than placebo cream in improving fine wrinkles according to the results at weeks 12 and 24 (P = 0.010 and P = 0.012, respectively). Significant improvement from baseline was detected in both groups for roughness, laxity and mottled pigmentation and/or lentigines; however, there was no significant difference in these parameters between the two treatment groups. No subjects discontinued treatment for a safety reason. In conclusion, Premarin cream produced better results than the placebo cream; the difference was statistically significant for skin thickness and fine wrinkles. Premarin cream was well tolerated locally, and its general safety was good.

Vail-Smith K; Felts WM
Health, Physical Education, Recreation, and Safety Program, East Carolina University, Greenville, North Carolina.
J Am Coll Health (United States) Jul 1993, 42 (1) p21-6

This study assessed the knowledge, attitudes, and behaviors of college students regarding intentional sun exposure (sunbathing). Results are based on responses of 296 Caucasian students to the Sun and Skin Inventory. Frequent sunbathers were more likely than infrequent sunbathers to be women and to report fewer self-perceived risk factors, and were less likely to use sunscreen . They were also more likely to believe that they look better with a tan, that suntanned skin is more attractive, and that suntans look healthy. Forty-three percent of the female respondents and 61% of the men rarely, if ever, used sunscreens, and only 9% of all respondents reported they used sunscreens with every intentional sun exposure of 30 minutes or longer. These results suggest that concern with attractiveness appears to be a major motivation for frequent intentional sun exposure. Consequently, educational strategies that stress health outcomes only may be less effective than those that also stress photoaging, the detrimental cumulative effect to appearance of suntanning.

Green LJ; McCormick A; Weinstein GD
Department of Dermatology, University of California, Irvine.
Dermatol Clin (United States) Jan 1993, 11 (1) p97-105

The appearance of photoaged skin is cosmetically unacceptable to many in our society. Ostensibly, avoidance of ultraviolet light and sunlight from early childhood is most desirable but not likely to happen in our culture. Tretinoin is the only pharmacologic compound shown to partially reverse some signs of photoaging. Improvement with tretinoin therapy has been quantified clinically and histologically. A major degree of improvement occurs in 6 to 12 months, and maintenance treatment one to three times per week may continue this response. Tretinoin therapy should optimally be used with daily moisturizer and sunscreen applications. Psychosocial benefits of tretinoin therapy, use of tretinoin for intrinsically aged or non-Caucasian skin, and higher-strength tretinoin therapy for severely photoaged skin need to be further explored. It is possible that some subsets of patients with photoaged skin may respond better than others. (25 Refs.)

Fourtanier A; Labat-Robert J; Kern P; Berrebi C; Gracia AM; Boyer B
L'OREAL, Laboratoire de Recherche Fondamentale, Aulnaysous-bois, France.
Photochem Photobiol (England) Apr 1992, 55 (4) p549-60

In a previous study on the hairless mouse it was shown that sub-erythemal doses of pure UV-A enhanced the numerous changes normally observed during chronological aging. A new sunscreen (a bis-benzylidene campho sulfonic acid derivative) has been synthesized in our research laboratory (lambda max: 345 nm, epsilon: 47,000). Its photoprotective properties against UV-A induced damages were assessed in our mouse model. Three month old albino hairless mice were exposed for 1 y to suberythemal doses (35 J/cm2) of UV-A obtained from a xenon source filtered through a WG 345 filter. One group of animals was exposed untreated, the other received a formulation containing 5% of the sunscreen prior to irradiation. At the end of the study the cutaneous properties of protected mice were compared to those of unprotected animals and to 3 and 15 month old unirradiated controls. We found that the visible changes induced by UV-A irradiation were mainly sagging and wrinkling. Histological and electron microscopic alterations consisted of hyperkeratosis, increased density of elastic fibers with alteration of fiber orientation and increased glycosaminoglycan deposits. Biochemical changes consisted of decreases in total collagen and collagen hydroxylation and increases in both collagen III/I + III ratio and fibronectin biosynthesis. All these changes were reduced or abolished by the sunscreen .

Elmets CA; Vargas A; Oresajo C
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio.
Photodermatol Photoimmunol Photomed (Denmark) Jun 1992, 9 (3) p113-20

It has become common practice to add sunscreening agents of variable potency to cosmetics to protect against the adverse effects of ultraviolet (UV) radiation exposure. The purpose of this study was to determine whether cosmetic preparations containing sunscreening agents protected against the adverse effects of acute UV radiation exposure and, if so, to identify the components responsible for the photoprotective effects. Pretreatment of skin with one such cosmetic product provided complete protection against UV-induced erythema, sunburn cell formation and Langerhans cell damage in volunteers, skin types II and III, whose skin was exposed to a 1.5 minimal erythema dose daily for 4 consecutive days. When individual components of the cosmetic preparation were analyzed for their photoprotective activities, it was found that both the cinnamate and benzophenone sunscreen combination and an extract of baker's yeast present in the preparation had photoprotective properties. These studies indicate that incorporation of photoprotective agents into cosmetic preparations provides a beneficial function and should therefore be encouraged.

Caputo R; Monti M; Rigoni C; Pinelli S; Motta S; Barbareschi M
First Department of Dermatology and Paediatric Dermatology, University of Milan, Italy.
Br J Dermatol (England) Sep 1992, 127 Suppl 41 p51-3

In a previously reported study on the anti-photoageing effects of topical tretinoin, the following regimen produced good patient compliance: 0.01% for 1 month, 0.025% for 1 month; and 0.05% for 4 months. The majority of patients (60/89) enrolled in the initial study continued to apply the cream to the face, and a further 140 patients were enrolled for a long-term study (mean duration 2 years). The prolonged study showed that 91.4% of patients used tretinoin in an attempt to slow down skin aging , and 8.6% sought subjective skin benefits. Of the 163 patients who completed the study, 58.8% sought an improvement of wrinkles, 30.1% skin trophism and 14.7% reduced pigmentation. The product was used throughout the year by 66.9% of patients, but 8.0% stopped using it during the summer. A daytime moisturizing cream was required by 77.9% of patients, and 82.8% used a sunscreen in the summer. Tretinoin was applied to other areas of the body by 63.8% of patients.

Jackson EM
Dermatol Nurs (United States) Jun 1992, 4 (3) p205-7

Facial moisturizers are part of the cosmetic category known as skin care products, which also includes other facial products such as astringents, toners, soaps, and bath products. This article describes the composition and pharmaceutics of currently marketed moisturizers, the use of fragrances and preservatives in these products, how cosmetic facial moisturizers work on wrinkles, sunscreen -containing facial moisturizers, and the Food and Drug Administration's record regulating drug claims for anti-wrinkling products.

Harrison JA; Walker SL; Plastow SR; Batt MD; Hawk JL; Young AR
Photobiology Unit, United Medical School of Guy's Hospital, University of London, United Kingdom.
Photodermatol Photoimmunol Photomed (Denmark) Feb 1991, 8 (1) p12-20

We examined the chronic effect of long daily suberythemal, fluorescent solar-stimulated radiation (FSSR; ultraviolet B (UVB)+A(UVA)) and UVA alone on female Skh-1 hairless albino mouse skin. Mice were dorsally irradiated 8 h every weekday for 16 weeks with FSSR or UVA, or 32 weeks with UVA alone. Various topical, low concentration, UVB and/or UVA sunscreens were applied before irradiation. Damage was assessed by skin-fold thickness, histology and biochemically by changes in the proportion of type III collagen. All FSSR-exposed mice showed increased skin thickening, elastic fibre hyperplasia, collagen damage and an increased proportion of type III collagen. Application of the UVB sunscreen (2.00%) resulted in marked protection for all nonbiochemical endpoints. There was no obvious advantage of adding 0.75% UVA sunscreen to the UVB sunscreen , but adding 2.00% UVA sunscreen reduced biochemical changes and connective tissue damage. Sixteen weeks of UVA irradiation caused skin thickening and laxity but the histology and biochemistry were indistinguishable from the controls. The mice irradiated with UVA for 32 weeks showed slight elastic fibre hyperplasia and collagen damage histologically, and increased skin thickening and laxity; these changes were unmodified by the 0.75% UVA sunscreen. These mice showed a significant increase in the proportion of type III collagen against which the UVA sunscreen offered protection. Our data suggest that UVA may be important in photoaging and that the use of low sun protection factor UVB+ UVA sunscreens on a day-to-day basis may offer some protection from solar photoaging.

Bissett DL; McBride JF; Hannon DP; Patrick LF
Procter and Gamble Co., Miami Valley Laboratories, Cincinnati, OH 45239-8707.
J Photochem Photobiol B (Switzerland) Jun 1991, 9 (3-4) p323-34

To determine the time dependence of sunscreen protection against chronic photodamage in hairless mice, the time was varied (0-8 h) between topical sunscreen treatment and UVB radiation exposure. Sunscreen products with labeled sun protection factor (SPF) values of 2, 4 and 8 were evaluated; these values were verified in a guinea pig model for SPF determinations. When applied immediately prior to UVB radiation exposure, these sunscreen products were very effective in prevention of skin wrinkling and tumor formation. Onset of photodamage was delayed, the delay being greater with higher SPF values. However, the sunscreen actives were rapidly lost from the skin surface, and their protective effect diminished strikingly as the time between treatment and irradiation increased. For daily protection against chronic photodamage, this suggests a need for photoprotectants with greater substantivity to achieve a high level of protection throughout the day.

Lowe NJ
University of California, Los Angeles School of Medicine.
J Dermatol Surg Oncol (United States) Oct 1990, 16 (10) p936-8

It has been well established in both human and animal skin that ultraviolet radiation from both ultraviolet B (UVB) (290 nm-320 nm) and ultraviolet A (UVA) (320 nm-420 nm) can produce profound changes in the skin that with recurrent exposure, cause it to become what we recognize as photoaged skin. Experimental studies in animals have confirmed that some sunscreen chemicals are capable of providing protection against ultraviolet-induced photoaging. It is presumed that regular use of these effective sunscreens will also reduce skin aging changes in humans. (14 Refs.)

Hawk JL
Photobiology Unit, St Thomas's Hospital, London, U.K.
Br J Dermatol (England) Apr 1990, 122 Suppl 35 p29-36

Photosensitivity to drugs and chemicals in the elderly is more prevalent due to more frequent use of medications. Phototoxic reactions to common, orally administered drugs such as diuretics, cardiac agents and antidiabetics may occur and the reactions may be remedied by discontinuing drug therapy. Photocontact dermatitis due to the ingredients in sunscreens or other agents, such as perfumes, may also arise. Diagnosis is often confirmed by photopatch testing and subsequent avoidance of these agents leads to gradual resolution. Idiopathic photodermatoses, such as sunlight-induced polymorphic light eruption or solar urticaria, may occur and persist from an early age and, in elderly subjects, they can cause mild to marked disability. The most disturbing disorder of this type is the severe, widespread eczematous chronic actinic dermatitis, which can be difficult to diagnose. Porphyrias, such as variegate porphyria or erythropoietic protoporphyria, may persist from an early age, whereas porphyria cutanea tarda generally begins in later life. Porphyrias all have specific clinical and biochemical features and, apart from variegate porphyria, usually respond well to treatment following diagnosis. Exposure of elderly skin to sunlight may also cause deterioration of many ordinary dermatoses, particularly seborrhoeic eczema, which generally respond to protection from UV exposure and to treatment of the underlying abnormality. Progress in identifying the underlying causes, the availability of increasingly sophisticated diagnostic techniques, and improvements in sunscreen preparations and therapeutic medications will probably significantly reduce abnormal photosensitivity in the elderly in the near future. (44 Refs.)

Young AR
Institute of Dermatology, United Medical School of Guy's Hospital, London, U.K.
Br J Dermatol (England) Apr 1990, 122 Suppl 35 p111-4

The most reliable way to reduce the chronic effects of solar UV radiation is to limit exposure. Animal data using hairless albino mice suggest that the routine use of sunscreens, which usually act as UVB (280-315 nm) filters, may prevent or inhibit skin photocarcinogenesis and photoageing in man. Conditions of chronic use of sunscreens in human skin, however, are not established but it is possible that, under some circumstances, sunscreen use could enhance skin cancer risk. The use of sunscreens may prevent or inhibit both sun-induced cancers and photoageing, but as yet there is no established method of designating the efficacies of sunscreens for the prevention of the chronic effects of solar UV radiation. This is an important research objective. (31 Refs.)

Griffiths C.E.M.
Prof. C.E.M. Griffiths, Section of Dermatology, Phase II, Hope Hospital, Eccles Old Road, Salford M6 8HD United Kingdom
cgriffit@fs1.ho.man.ac.uk
Drugs and Aging (New Zealand) 1999, 14/4 (289-301)

Although the prevention of skin aging is a holy grail of the cosmetic and pharmaceutical industries, this venture may be misplaced. The predominant clinical and biochemical features of aged skin are mostly attributable to photoaging rather than chronology. For instance chronic sun exposure is the major determinant of age spots (actinic lentigines) and wrinkles. Surgical approaches to the treatment of photoaging include face-lift, dermabrasion, chemical peeling, collagen and botulinum toxin injections, and laser re-surfacing. These approaches all have benefit and improve the clinical features of facial photoaging. Drug or pharmaceutical prevention and treatment of photoaged skin is still in its infancy. The main pharmaceutical approach to prevention of photoaging lies in the assiduous use of sunscreens. Recent evidence points to the importance of ultraviolet A (UVA) radiation as well as ultraviolet B (UVB) radiation in the aetiology of photoaging and thus the need fur sunscreens that block both UVB and UVA. Drug treatment of photoaged skin can be categorised as antioxidants, alpha-hydroxy acids and topical retinoids. Of these 3 approaches only topical retinoids, particularly tretinoin (all-trans retinoic acid), have a well documented ability to repair photoaged skin at the clinical, histological and molecular level. Furthermore, the use of topical retinoids may actually prevent photoaging. The current interest in pharmaceutical modulation of the photoaging process has attracted considerable research into the mechanisms of photoaging and cutaneous aging. It is likely that treatment for, or prevention of, the chronological aging process may result from such research.

Uitto J.; Bernstein E.F.
Dr. J. Uitto, Dept. of Dermatol./Cutaneous Biolgy, Jefferson Medical College, Bluemle Life Sciences Building, 233 S. 10th Street, Philadelphia, PA 19107-5541 United States
Journal of Investigative Dermatology Symposium Proceedings (United States) 1998, 3/1 (41-44)

Cutaneous aging is a complex biological phenomenon consisting of two distinct components, (a) the intrinsic, genetically determined degenerative aging processes and (b) extrinsic aging due to exposure to the environment, also known as 'photoaging'. These two processes are superimposed in the sun- exposed areas of skin, with profound effects on the biology of cellular and structural elements of the skin. This overview summarizes our current understanding of the mechanisms of innate versus extrinsic aging with emphasis on connective tissue alterations, primarily collagen and the elastic fiber network. We also introduce a novel transgenic mouse model, expressing a human elastin promoter-reporter gene construct, suitable for studies on biology and preventive pharmacology of the cutaneous aging.

Torras H.
H. Torras, Servei Dermatologia, Hospital Clinic Provincial, Villarroel 170, 08036 Barcelone Spain
Nouvelles Dermatologiques (France) 1998, 17/4 (249-252)

Cosmetology is the science of art of treating and improving the appearance of healthy skin. It is almost as old as humanity. Until a few years ago, dermatology was only concerned with skin pathology. Cosmetology was mostly chemical, it was concerned with the formulation of products for modifying an aesthetic defect or improving the appearance of ski. At that time, communication between dermatology and Cosmetics was quite limited. Today, 'Cosmetic dermatology' is concerned with skin problems that are expression of a skin dysfunction. So who must take care of skin aging caused by the sun protection or seborrheic or dry skin? The logical answer is the dermatologist. During the last 20 years, the number of dermatologists in Spain has doubled, and this is one of the reasons for the increase in cosmetic dermatology prescriptions. In 1973, 'cosmeceuticals' for the skin represented 30% of total OTC products. In 1993 this percentage rose to 64.7% or more than double. The recent evolution of Cosmetic dermatology and the growing interest shown by dermatologists are demonstrated by several facts: - they often prescribe skin care for normal skin, which was rare 20 years ago; - they make a more precise evaluation of skin type; - they are more interested in Cosmetics and skin aging treatments; - there are more prescriptions for 'cosmeceutical lines'. In the future, socioeconomic progress shall increase the development of new products. European countries will show a progressive increase in homogenization, but certain national differences, specific to the culture of each country or region, will remain.

Won Y.H.; Yoo Y.E.; Lee S.C.; Kim Y.P.; Chun I.K.
Department Dermatology, Chonnam University Medical School,Kwangju 501-757 South Korea
Annals of Dermatology (South Korea) 1995, 7/4 (288-294)

Background: Sunscreens have been used widely to prevent the photosensitive skin diseases, skin cancer, and skin aging . However, no sunscreen blocks all kinds of effects caused by ultraviolet light(UVL), and the effect of sunscreens on the impairment of immune function by UVL irradiation is controversial. Objective: We try to evaluate the efficiency of sunscreens for blocking the depletion of LC induced by UVB irradiation. Method: The ATPase positive LCs were observed in the skin of hairless mice(Hr+/Kud) irradiated by UVB with or without topical application of sunscreens. Two commercially available sunscreens with respective SPF 8 and SPF 30 were applied to the dorsal trunk skin. The mice were irradiated with different increasing doses of UVB at a single time. Results: The ATPase positive LCs in the irradiated dorsal and ear skin were significantly decreased in densities according to the dosage, and apparently revealed a loss of their dendrites, granulation, and clumping from a UVB dose of more than 60mJ/Cmsup 2. With both sunscreen treatment on the dorsal trunk before irradiation, the densities of LCs on the dorsal skin were significantly higher compared to the untreated groups at all ranges of UVB doses in spite of a dose dependent decrease in their density. However there was no significant difference on their preventive effect between both sunscreens(SPF 8 and SPF 30) except at high UVB doses of more than 240 mJ/Cmsup 2. Conclusion: The LC depletion induced by UVB can be partially protected through the topical application of a sunscreen at a UVB dose dependent fashion. However SPF(sun protective factor) dose not appear to be a good indicator for evaluating sunscreens immunologically.

Harth Y.; Schemer A.; Friedman-Birnbaum R.
Department of Dermatology, Rambam Med. Cter., Faculty Med.,Haifa 31096 Israel
Journal of the European Academy of Dermatology and Venereology (Netherlands) 1995, 4/3 (260-266)

Objective. There is accumulating evidence that in spite of the large campaigns against excessive solar exposure undertaken by dermatologists worldwide, children and adolescents are still spending long periods in the sun, and do not follow the recommended sun protection guidelines. The purpose of the present study was to evaluate sun exposure in a group of young Israeli adults and to compare it to their knowledge and application of the various sun protection methods. Methods. 202 Caucasian volunteers, (mean age 21.4 +/- 2.6), filled out detailed questionnaires on their sun exposure and sun protection habits. Results. More than 80% of our study participants are regularly sun exposed for longer than 2 h per day whereas sunscreens are utilized only by 64.9%. Sunscreen use was significantly more prevalent in females than males (81.3% vs. 46.5%). The majority of sunscreen users and nonusers believed that sunscreen could prevent skin cancer (94.3% and 82.0%, respectively) and that these compounds can slow skin aging (90.8% and 76.4% respectively). The understanding of the meaning of the 'SPF' was significantly higher in the sunscreen users (85%) than in the nonusers (62.0%). The majority of sunscreen users utilized less than 150 ml of the compound per year which is probably an inadequate amount for a year for full body protection. The two most common reasons for-not using sunscreens regularly; were that the application is time consuming, and that sunscreens prevent tanning. Conclusion. Our data reveals a discrepancy between a considerably good understanding of the need for sun protection and the still deficient application of these measures especially in young adult males.

Continued on the next page...

The aging face: Medical versus surgical treatments

Freeman M.
Modern Medicine of Australia (Australia), 1997, 40/3 (36-39+41-42)

The aging process involves us all and is affected by endogenous and exogenous factors. Skin texture changes consistent with moderate to severe aging have been observed in 72% of men and 47% of women under 30 years of age in Queensland. Photo aging among men of all ages has been associated with outdoor occupations, outdoor leisure activities, a tendency to sunburn and previous skin cancer. There are also syndromes that have premature aging as their major feature. Indicators of aging such as grey hair, reduced skin elasticity and arcus senilis are strongly and independently related to chronological age. Prevention is important in minimising photoaging, and for aging skin in general there are medical and surgical treatments that may help.

Suppression of UV-induced erythema by topical treatment with melatonin (N-acetyl-5-methoxytryptamine). A dose response study

Bangha E.; Elsner P.; Kistler G.S.
Department of Dermatology, University of Zurich, Gloriastr 31, CH-8091 Zurich Switzerland
Archives of Dermatological Research (Germany), 1996, 288/9 (522-526)

Oxygen-centred free radicals play an important role in the pathogenesis of acute and chronic UV-induced skin damage as well as in skin aging. In this double-blind randomized study the efficacy of topicacetyl-5-methoxyt ryptamine), a potent free radical scavenger, in the suppression of UV-induced erythema was assessed. A group of 20 healthy volunteers were irradiated with 0.099 J/cm2 UVB on four 5-cm2 areas on the lower back and topically treated with various concentrations of melatonin (0.05, 0.1, 0.5%) in a nanocolloid gel as carrier or with carrier alone. The UV-induced erythema was examined 8 and 24 h after irradiation by visual scoring and chromametry. A distinct dose response relationship was observed between the topical dose of melatonin and the degree of UV-induced erythema. Significant differences (P < 0.05) were found in redness (chromameter a(*)-value and visual scoring) 8 h after irradiation between the areas treated with melatonin at 0.5% and those treated with melatonin at 0.05% or with the carrier. These results might open a new approach in the prevention and control of free radical-influenced skin diseases.

Photodermatitis and early aging of the skin. Significant regeneration by high dose vitamin A and E

Trieloff I.
Germany
TW Dermatologie (Germany), 1996, 26/2 (136-137)

(Abtract not available)

Sunscreens: The ounce of prevention

Wentzell J.M.
Billings Clinic, 2825 8th Ave. N., Billings, MT 59107-5100 USA
American Family Physician (USA), 1996, 53/5 (1713-1719)

Sun exposure is linked to visible signs of skin aging, skin cancer, photodermatoses, exacerbation of systemic disease and photoallergic, as well as phototoxic, drug eruptions. Sunscreens very considerably in their ability to protect patients from exposure to ultraviolet light and its effects. Inappropriate choice and use of sunscreen products can lead to worse problems than using no sunscreen at all. Controversies about sunscreen include adequate level of sun protection factor, appropriate age of users, and whether use of sunsfincreen products can prevent skin cancer. Instructing patients in how to select end use sunscreen can help prevent or mit end systemic diseases.

Alpha hydroxy acids in the cosmetic treatment of photo-induced skin aging

Morganti P.; Randazzo S.D.; Bruno C.
Department of Dermatology, Dermatologists Training School, II University of Naples, Naples Italy
Journal of Applied Cosmetology (Italy), 1996, 14/1 (1-8)

The continuous adverse effects of light of over the years add to normal aging processes. This increases the number and severity of wrinkles, reduces the efficiency of cell mechanisms responsible for the reparation of damaged genes due to UV rays in photo-exposed areas, causes actinic keratosis, slows down epidermic cell turnover and reduces surface lipids, the moisture level and, as a result, the suppleness of the skin. The noticeable adverse effects generally decrease with the use of retinoic acid-based drugs or cosmetic-based products including various active components, from collagen to sodium lactate and aminoacids, from gelatine-glycine to Pyrrolidone Carboxylic Acid (PCA) and the newly-used Alpha hydroxy acids (AHAs), such as, for example, glycolic acid. This double-blind study aims to control the activity of 8% AHAs and gelatin-glycine-based cosmetic emulsions over 90 days clinically evaluating the number of thin wrinkles. Furthermore, the surface lipid film, the pH value and the skin moisture level were tested with the computerized methodology 3C System (R). Finally, the cell turnover was tested with the 'Scrub technique'.

Skin photosensitizing agents and the role of reactive oxygen species in photoaging

Dalle Carbonare M.; Pathak M.A.
Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114 USA
J. Photochem. Photobiol. B Biol. (Switzerland), 1992, 14/1-2 (105-124)

In this paper, the role of reactive oxygen species in photoaging is presented. Many photosensitizing agents are known to generate reactive oxygen species (singlet oxygen (1O2), superoxide anion (O2.-) and .OH radicals). Although photoaging (dermatoheliosis) of human skin is caused by UVB and UVA radiation, the hypothesis tested here in the pathogenesis of photoaging of human skin is the free radical theory involving the generation of reactive oxygen species by UVA (320-400 nm) radiation and their damaging oxidative effects on cutaneous collagen and other model proteins. The UVA-generated reactive oxygen species cause cross-linking of proteins (e.g. collagen), oxidation of sulfydryl groups causing disulfide cross-links, oxidative inactivation of certain enzymes causing functional impairment of cells (fibroblasts, keratinocytes, melanocytes, Langerhans cells) and liberation of proteases, collagenase and elastase. The skin-damaging effects of UVA appear to result from type II, oxygen-mediated photodynamic reactions in which UVA or near-UV radiation in the presence of certain photosensitizing chromophores (e.g, riboflavin, porphyrins, nicotinamide adenine dinucleotide phosphate (NADPH), etc.) leads to the formation of reactive oxygen species (1O2, O2.-, .OH). Four specific observations are presented to illustrate the concept: (1) the production of 1O2 and O2.- by UVB, UVA and UVA plus photosensitizing agents (such as riboflavin, porphyrin and 3-carbethoxypsoralens) as a function of UV exposure dose, the sensitizer concentration and the pH of the irradiated solution; (2) the formation of protein cross-links in collagen, catalase and superoxide dismutase by 1O2 and O2.- (.OH) and the resulting denaturation of proteins and enzyme activities as a function of UVA exposure dose; (3) the protective role of selective quenchers of 1O2 and O2.- (e.g. alpha-tocopherol acetate, beta-carotene, sodium azide, ascorbic acid, etc.) against the photoinactivation of enzymes and the prevention of the protein cross-linking reaction; (4) the possible usefulness of certain antioxidants or quenchers that interact with the UVA-induced generation of reactive oxygen species in the amelioration of the process of photoaging.

An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

Pelle E.; Maes D.; Padulo G.A.; Eun-Kyung K.; Smith W.P.
Estee Lauder Research and Development, Melville, NY 11747 USA
Arch. Biochem. Biophys. (USA), 1990, 283/2 (234-240)

Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA > catechin > BHT > alpha-tocopherol > chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation.

Diminished stimulation of hyaluronic acid synthesis by PDGF, IGF-I or serum in the senescence phase of skin fibroblasts in vitro

Schachtschabel D.O.; Freudenstein G.
Institut fur Physiologische Chemie, Philipps-Universitat, Karl-von-Frisch-Strasse 1, 35033 Marburg Germany
Z. Gerontol. (Germany), 1994, 27/3 (177-181)

Human skin fibroblasts of phase II ('young' cells derived from populations with a low population doubling level) and of phase III ('old' cells from populations, which were approx. 2 population doublings before the last possible subculture) were kept under subconfluent conditions in a defined serum-free medium. Thereby the cells are in a non-proliferative 'quiescent' state. Glycosaminoglycan (GAG)- and especially hyaluronan (HA)-synthesis and release into the medium were investigated by the incorporation rate of 14C-glucosamine. About 95% of the synthesized (48 h) GAGs and HA were medium-released and 5% cell-bound. HA synthesis rate of Phase III-cultures was significantly reduced, as compared with phase II-cultures. Stimulation of HA-synthesis of phase III-cells - in comparison with phase II-cells - by serum, PDGF or IGF-I was strongly reduced. While HA-synthesis of phase II-cells was maximally stimulated by 5% FCS or 20 ng/ml PDGF, phase III-cells did not exhibit a saturation kinetics up to 20% FCS or 60 ng/ml PDGF. The strongly reduced HA-synthesis rate of phase III-cells - compared with phase II-cells - in the non-stimulated quiescent state as well as after stimulation by PDGF, IGF-I or serum might be considered as a biomarker of in vitro (and in vivo?) aging.

Ultrastructural study of hyaluronic acid before and after the use of a pulsed electromagnetic field, electrorydesis, in the treatment of wrinkles

Ghersetich I.; Teofoli P.; Benci M.; Lotti T.
Department of Dermatology, University of Florence, Via Alfani 37, 50121 Florence Italy
Int. J. Dermatol. (Canada), 1994, 33/9 (661-663)

Background. Treatment of wrinkles has become an increasing problem for dermatologists. Hyaluronic acid is a component of the family of glycosaminoglycans (GAGS, substances known for their property of retaining water), that significantly decreases with aging and in wrinkles. A new technique that uses a specific pulsed electromagnetic field, electrorydesis, has been introduced in the treatment of wrinkles associated with aging. The treatment is based on the reported in vitro effects of specific electromagnetic fields on fibroblast cultures (e.g., an increase in DNA synthesis and in the production of collagen and presumably also of GAGS).

Methods. The in vivo effects of the electromagnetic field on aged skin (3 subjects aged 50, 56 and 60 years), with particular focus on the ultrastructural modifications and GAGS amount before and after the treatment, were evaluated by electron microscope.

Results. The ultrastructural study (tissue stained with alcian blue) showed after treatment a significant increase (p < 0.005) of the electron-dense granules (corresponding to hyaluronic acid), located in collagen elastic fibers, and in the soluble matrix. This presumably leads to subsequent edema that was clinically evident after the treatment.

Conclusions. These data suggest that the increased levels of GAGS and the subsequent edema of the dermis could explain at least in part the clinical changes observed after electrorydesis treatment (e.g., swelling and 'disappearance' of the wrinkle).

Hyaluronic acid in cutaneous intrinsic aging

Ghersetich I.; Lotti T.; Campanile G.; Grappone C.; Dini G.
23, via Alighieri, 51016 Montecatini Terme (PT) Italy
Int. J. Dermatol. (Canada), 1994, 33/2 (119-122)

Background. In elderly individuals all components of the skin and subcutaneous tissue undergo histologic and ultrastructural changes. The turgidity of the dermis appears decreased, presumably due to altered patterns and levels of glycosaminoglycans (GAGS), especially hyaluronic acid and dermatan sulfate that are the most common. A linear, age-related decrease in the content of GAGS (mainly hyaluronic acid) has been hypothesized in human aged skin.

Methods. We used the cationic dye Alcian Blue to selectively stain hyaluronic acid within the dermis in old and young subjects to compare ultrastructurally its topography and variations with age.

Results. We demonstrated a progressive reduction in the number of electron-dense granules of hyaluronic acid and of their filaments until they were completely absent in subjects aged 60. Conclusions. We propose that the variations of the levels of hyaluronic acid in the dermis in aging could account for some of the most striking alterations of the aged skin, including decreased turgidity, less support for microvessles, wrinkling, and altered elasticity.

Stimulation of cell proliferation by hyaluronidase during in vitro aging of human skin fibroblasts

Moczar M.; Robert L.
LBTC CNRS URA 1460, Faculte de Medecine, Universite Paris XII, 94010 Creteil Cedex France
Exp. Gerontol. (USA), 1993, 28/1 (59-68)

The effect of the degradation of extracellular hyaluronan on the proliferation of human skin fibroblasts in serial cultures during in vitro aging was investigated. Human skin fibroblasts at different time intervals from 3rd to 36th passages were exposed after plating to bovine testicular hyaluronidase. The enzyme treatment resulted in an increase in cell proliferation (cell number vs. time) as compared to the untreated control fibroblasts. The effect was dose dependent, reversible, and was independent of the type of the glycosidic linkage cleaved in hyaluronan. The increased proliferation was observed at all passages when untreated cells underwent mitosis. The degradation of hyaluronan induced cell proliferation up to the presenescent phase. Depletion of hyaluronan did not induce proliferation of postmitotic fibroblasts. The incorporation of 3H-glucosamine into hyaluronan decreased with increasing cell passages (increase of the number of population doublings). Twenty-fourth passage fibroblasts accumulated about two time less hyaluronan in the medium than ninth passage cultures. Following hyaluronidase treatment, the amount of newly synthesized, labeled hyaluronan increased in the medium. Accordingly, the fibroblasts restored the degraded hyaluronan even in the declining phase of proliferation (phase III according to Hayflick).

Topical retinoic acid treatment of photoaged skin: Its effects on hyaluronan distribution in epidermis and on hyaluronan and retinoic acid in suction blister fluid

Lundin A.; Berne B.; Michaelsson G.
Department of Dermatology, University Hospital, S-751 85 Uppsala Sweden
Acta Derm.-Venereol. (Norway), 1992, 72/6 (423-427)

Topical treatment with retinoic acid (tretinoin, vitamin A acid) has been reported to partly reverse signs of photodamage. To determine whether the histochemical distribution of hyaluronan (hyaluronic acid, HYA) in the epidermis and dermis and the amounts of HYA and retinoic acid in suction blister fluid were influenced by such topical treatment, 14 subjects healthy apart from moderate photodamage were instructed to treat the lateral forearm with 0.01-0.05% retinoic acid cream for 6 months. In a study of the short-term effects, another six subjects applied 0.05% retinoic acid cream for 2 weeks. After 6 months the thickness of the vital epidermis had increased by 23%. The HYA staining was based on a specific immunohistochemical method in which hyaluronan-binding protein is used. Before treatment HYA was seen as a meshwork around the cells in the upper half of the stratum spinosum. After 6 months of treatment this meshwork had increased in thickness by 31% compared with pretreatment specimens. The HYA staining was already intense in the papillary dermis before treatment and no difference was observed after 6 months' treatment. The mean concentration of HYA in blister fluid had increased significantly (43%) after 2 weeks of treatment whereas after 6 months there was no significant difference in this respect between the treated and untreated arm. The increase in the thickness of the epidermal HYA meshwork after 6 months and the blister fluid HYA after 2 weeks may indicate that HYA is involved in the epidermal change induced by topical retinoic acid therapy. The mean concentration of retinoic acid in suction blister fluid after 2 weeks of treatment was 328plus or minus63 nM whereas before treatment retinoic acid was usually not detectable. After 6 months of treatment the mean retinoic acid concentration was 73plus or minus33 nM. The mechanisms for the lower retinoic acid values at 6 months compared with those at 2 weeks are unknown.

Werner's syndrome: Biochemical and cytogenetic studies

Gawkrodger D.J.; Priestley G.C.; Ross J.A.; et al.
Department of Dermatology, University of Edinburgh, Royal Infirmary, Edinburgh United Kingdom
Arch. Dermatol. (USA), 1985, 121/5 (636-641)

Werner's syndrome is a rare condition of autosomal-recessive inheritance, showing some features of accelerated aging. We describe the clinical findings and laboratory studies in a 29-year-old man with this disorder, who presented because of a leg ulcer. Skin fibroblasts from our patient were difficult to culture and proliferated more slowly than those of controls. They produced less glycosaminoglycans than those of controls but synthesized more collagen, which was normal in type. The patient's urinary glycosaminoglycan level was slightly elevated, with hyaluronic acid as a major component. His peripheral blood lymphocytes showed no chromosomal instability and responded normally to mutagens.

Urinary acidic glycosaminoglycans in Werner's syndrome

Murata K.
Dept. Med. Phys. Ther., Univ. Tokyo Sch. Med., Bunkyo-ku, Tokyo 113 Japan
Experientia (Switzerland), 1982, 38/3 (313-314)

The composition of urinary acidic glycosaminoglycans (AGAG) in 4 patients with Werner's syndrome was determined by an enzymatic assay system using chondroitinases and hyaluronidase. In Werner's syndrome, the amount of hyaluronic acid and heparan sulfates in the total AGAG increases. A compositional change in the chondroitin sulfate isomers occurs. The change of urinary AGAG in Werner's syndrome appears to reflect age-related changes.

Non-enzymatic degradation of acid-soluble calf skin collagen by superoxide ion: Protective effect of flavonoids

Monboisse J.C.; Braquet P.; Randoux A.; Borel J.P.
Lab. Biochim. Med., Fac. Med. Reims, 51095 Reims Cedex France
Biochem. Pharmacol. (England), 1983, 32/1 (53-58)

Calf skin acid-soluble collagen in microfibrillar form was incubated with free oxygen radicals produced by the system xanthine oxidase + hypoxanthine. This incubation liberated peptides of a size smaller than that of alpha-chains, as demonstrated by SDS-PAGE and by evaluation of the 4-hydroxyproline contained in small peptides. The amount of liberated peptides was found to increase with time. The process was inhibited by addition of superoxide dismutase to the medium but not by addition of catalase. Two flavonoids extracted from bilberries and a third one from grapes were demonstrated to protect collagen against this non-enzymatic proteolytic activity. This work confirms that collagen may be degraded during the process of inflammation and that some flavonoids are endowed with protective properties.

In vitro cytotoxic effects of enzymatically induced oxygen radicals in human fibroblasts: Experimental procedures and protection by radical scavengers

Noel-Hudson M.S.; De Belilovsky C.; Petit N.; Lindenbaum A.; Wepierre J.
Faculte de Pharmacie, Unite de Dermopharmacologie, CNRS UA 594, 92290 Chatenay Malabry France
Toxicol. Vitro (United Kingdom), 1989, 3/2 (103-109)

Introduction of hypoxanthine and xanthine oxidase into human fibroblast cultures induces a dose-dependent cytotoxicity as a result of free-radical formation. The influence of medium, cell density and the power of recovery after free-radical attack were investigated. It appears that toxicity is higher in physiological Dulbecco phosphate buffer or Hanks' balanced salt solution than in modified Eagle medium, is inversely proportional to cell density and that damage is most often irreversible. Using this model, we studied the protective effects of a hydrosoluble flavonoid, silybin, and of a well known antioxidant, BHT (butylated hydroxytoluene). These molecules were administered before and during free-radical attack. With BHT significant protection was observed when it was added before free-radical attack (24%) protection at a concentration of 10-4 M) and before and during exposure (20% protection at a concentration of 10-5 M). When silybin is applied during radical attack maximal activity is recorded at a concentration of 8 x 10-4 M (45%), but the most interesting results are observed when 1 x 10-4 and 8 x 10-4 M are used, respectively, before and during radical exposure (63% of activity).

Antiviral activity of plant components. 1st Communication: flavonoids

Wacker A.; Eilmes H.G.
Abt. Therapeut. Biochem., Zent. Biol. Chem., Univ. Frankfurt/M. Germany, West
Arzneim.-Forsch. (Germany, West), 1978, 28/3 (347-350)

Some drugs effective against influenza contain flavonoids. The authors therefore examined the antiviral effect of hesperidin, hesperidinmethylchalcon, trihydroxyethylrutin, catechol, quercitrin, rutin and aurantiin against vesicular stromatitis virus (VSV) action on mouse fibroblasts and that of hesperidin against influenza virus in HeLa cells system by means of dye uptake measurements (Finter) and by plaque reduction test, respectively. Preincubation of the cells with the flavonoids 6-8 h before virus addition was inevitable. Protection of cells against virus action persisted for about 24 h and it abruptly disappeared after an addition of hyaluronidase. Maximal inhibition of virus action was achieved with a concentration of 200 mug/ml flavonoid.

Therapy of radiation damage in mice with O (L hydroxyethyl) rutoside

Bruckner V.
Inst. Biophys. Strahlenbiol., Univ. Hamburg Germany, West
Strahlentherapie (Germany, West), 1973, 145/6 (731-734)

In a mammalian organism a massive irradiation causes vascular damages induced by thrombocytopenia. This again leads to internal haemorrhages and the invasion of bacteria into the blood stream. Because of the lymphocytopenia and granulocytopenia also induced by radiation the resistance of an organism against infection is greatly reduced. Here the critical phase of the acute radiation syndrome begins, which often ends fatally. The authors therefore wondered whether it would be possible to obtain a treatment for the radiation damage in mice with a vaso stabilizing agent. As a suitable substance they chose the semi synthetic flavonol glycoside O (beta hydroxyethyl) rutoside. When this flavonoid was applied orally after the exposure, the survival rate of the whole body X irradiated mice was increased significantly from 31% to 56%. Because of the fact that this substance has already been in use for many years in human medicine there is perhaps a possibility of treating radiation sickness in men (e.g. the victims of radiation accidents in nuclear installations) successfully with this drug, since blood transfusions and especially bone marrow transplantations are still problematical.

Anti-aging active principals by the oral route. Myth or reality?

Frances C.
Groupe Hospitalier Pitie-Salpetriere, Unite de Dermatologie, 47-83 Boulevard de l'Hopital, 75651 Paris Cedex 13 France
Nouv. Dermatol. (France), 1994, 13/6 (423-425)

Beta-carotene, precursor of vitamin A, has an anti-tumoral effect which is demonstrated in animals but not in man. Vitamin A has anti-free radical properties, but there is a toxicity when ingested at doses above 5000 IU/kg/day. Local applications of Vitamin-C reduce the cutaneous phototoxicity of UVA and UVB in animals. Vitamin E or tocopherol is potentially one of the most interesting vitamins against cutaneous aging. The preventive role of selenium, which is an essential oligo-element, is shown in certain photo-induced epidermal cell damages but not in cutaneous aging.

Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin: A double-blind vehicle-controlled clinical trial

Stiller M.J.; Bartolone J.; Stern R.; Smith S.; Kollias N.; Gillies R.; Drake L.A.
Department of Dermatology, Massachusetts General Hospital, Boston, MA 02114 USA
Archives of Dermatology (USA), 1996, 132/6 (631-636)

Objective: To evaluate the efficacy and tolerability of 2 widely used topical alpha-hydroxy acids at low concentrations, 8% glycolic acid and 8% lactic (L-isoform) acid creams, in the treatment of photodamaged skin.

Design: A single-center, 22-week, double-blind, vehicle-controlled, randomized clinical trial assessed the overall severity of photodamage on the faces and forearms of volunteers, based on 7 individual clinical components of cutaneous photodamage.

Setting: The study was performed in an outpatient clinical research unit at the Massachusetts General Hospital, Boston.

Patient: Seventy-four women, aged 40 to 70 years, with moderately severe photodamaged facial skin were enrolled in the study. One subject withdrew from the study early because of skin irritation, and 6 subjects withdrew from the study for personal reasons. Interventions: Glycolic acid, L-lactic acid, or vehicle creams were applied twice daily to the face and outer aspect of the forearms.

Main Outcome Measures: Improvement in alpha-hydroxy acid-treated photodamaged skin as determined by patient self-assessments and physician evaluations of efficacy and irritancy.

Results: The percentage of patients using either 8% glycolic acid or 8% L-lactic acid creams on the face achieving at least i grade of improvement (using a scale from 0 through 9) in overall severity of photodamage was significantly greater than with the vehicle cream (76% glycolic acid, 71% lactic acid, and 40% vehicle; P<.05). On the forearms, after 22 weeks, treatment with glycolic acid cream was superior to the vehicle in improving the overall severity of photodamage and sallowness (P<.05). L-Lactic acid cream was significantly superior to the vehicle in reducing the overall severity of photodamage (P<.05), mottled hyperpigmentation (P<.05), sallowness (P<.05), and roughness on the forearms (P<.05) at week 22.

Conclusions: Topical 8% glycolic acid and 8% L-lactic acid creams are modestly useful in ameliorating some of the signs of chronic cutaneous photodamage. These agents are well tolerated and available without prescription.

Effects of alpha-hydroxy acids on photoaged skin: A pilot clinical, histologic, and ultrastructural study

Ditre C.M.; Griffin T.D.; Murphy G.F.; Sueki H.; Telegan B.; Johnson W.C.; Yu R.J.; Van Scott E.J.
NeoStrata Co., Inc., Princeton, NJ USA
Journal of the American Academy of Dermatology (USA), 1996, 34/2 I (187-195)

Background: alpha-Hydroxy acids (AHAs) have been reported to improve aging skin. The mechanisms of action of AHAs on epidermal and dermal compartments need clarification.

Objective: Our purpose was to determine the effects of AHAs on photoaged human skin by clinical and microanalytic means.

Methods: Patients applied a lotion containing 25% glycolic, lactic, or citric acid to one forearm and a placebo lotion to the opposite forearm for an average of 6 months. Thickness of forearm skin was measured throughout the study. Biopsy specimens from both forearms were processed for analysis at the end of the study.

Results: Treatment with AHAs caused an approximate 25% increase in skin thickness. The epidermis was thicker and papillary dermal changes included increased thickness, increased acid mucopolysaccharides, improved quality of elastic fibers, and increased density of collagen. No inflammation was evident.

Conclusion: Treatment with AHAs produced significant reversal of epidermal and dermal markers of photoaging.

Topical gelatin-glycine and alpha-hydroxy acids for photoaged skin

Morganti P.; Randazzo S.D.; Palombo P.; Bruno C.
I.S.C.D., Via Innocenzo XI, 41, 00165 Roma Italy
J. Appl. Cosmetol. (Italy), 1994, 12/1 (1-10)

Skin hydration and well-being are known to depend upon the amount of water in the horny layer. Hydration depends also on the level of NMF(S) (Natural Moisturizing Factors), thus on PCA (Pyrolydone Carboxylic Acid) and on the proper intensity of pespiratio insensibilis. This depends in turn on balanced surface lipidic film. So-called photoaging, connected with the amount of UV and light absorbed over a lifetime, causes a decrease in skin hydration and surface lipids and increase of fine wrinkling which results in early aging and skin xerosis. This work aims to demonstrate the rehydrating and lipid restoring action of different cosmetic emulsions. One hundred smoker women aging 52 to 63 have been investigated. They all frequented solar centers and were clearly affected by xerosis. They were treated with Gelatin-Glycine and Alpha Hydroxy Acids cosmetic emulsions for 120 days. Skin hydration and surface lipids were monitored through the new 3C System computerized equipment (Rome, Italy). Fine wrinkling was evaluated using a visual analog scale in subject randomly treated on one side by the active cream, the other side serving as control. Thanks to the increase from 36% and 82% in surface lipids and from 31% to 90% in horny layer hydration, and to the decrease of about 17% of fine wrinkling these cosmetic treatments seem adequate for premature skin aging caused by sun and environmental pollutants.

Antioxidants, fat and skin cancer

Sahl W.J.
717 Meade Street, Rapid City, SD 57701 USA
Skin Cancer (Portugal), 1995, 10/2 (97-101)

The incidence of actinic keratoses, basal cell carcinomas and squamous cell carcinomas increases proportionately with increasing cutaneous sun exposure. There is mounting evidence that dietary nutrients may play an important role in sun induced skin damage and skin cancer. In this brief discussion, the evidence is reviewed for a participatory interaction between ultraviolet radiation and dietary factors in cutaneous aging and carcinogenesis. In particular, this paper investigates the relationship between dietary antioxidants and cutaneous fat concentrations as the keys to understanding the possible relationship between diet and skin cancer.

Photoprotective effect of superoxide scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse

Bissett D.L.; Chatterjee R.; Hannon D.P.
Procter and Gamble Company, Miami Valley Laboratories, P.O. Box 398707, Cincinnati, OH 45239-8707 USA
Photodermatology Photoimmunology Photomedicine (Denmark), 1990, 7/2 (56-62)

Albino hairless mice (Skh: HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavening antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox (R)) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of super oxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.

Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation

Fuchs J.; Huflejt M.E.; Rothfuss L.M.; Wilson D.S.; Carcamo G.; Packer L.
Membrane Bioenergetics Group, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720 USA
J. Invest. Dermatol. (USA), 1989, 93/6 (769-773)

Antioxidants may play a significant role in ameliorating or preventing photobiologic damage in skin that could lead to cutaneous disorders such as cancer and premature aging. The objective of this study was to assess the acute cutaneous enzymic and nonenzymic antioxidant response to a single exposure of large fluence (300 mJ/cm2) ultraviolet radiation (>280 nm) in hairless mice. This treatment caused an immediate and statistically significant inhibition of glutathione reductase and catalase activity. Glutathione peroxidase and superoxide dismutase were not affected. Glutathione levels decreased and, conversely glutathione disulfide concentrations increased. A slight depletion of the total glutathione was observed, while the content of total ascorbic acid did not change. The lipophilic antioxidants alpha-tocopherol, ubiquinol 9 and ubiquinone 9 also decreased significantly, and the concentration of malondialdehyde remained constant. The free radical scavenging activity of epidermis, as assessed by reduction of the stable, cationic nitroxide radical (2,2,6,6-tetramethyl-1-piperidinoxy-4-(2',4',6'-trimethyl) methyl-pyridinium perchlorate) was considerably inhibited. The study indicates that immediately after exposure to a large fluence of ultraviolet radiation the enzymic and nonenzymic antioxidant capacity of skin decreases significantly.

Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people

Cederholm T.E.; Berg A.B.; Johansson E.K.; Hellstrom K.H.; Palmblad J.E.W.
Karolinska Institute, Department of Medicine, Stockholm Slider Hospital, S-118 83 Stockholm Sweden
Eur. J. Clin. Invest. (United Kingdom), 1994, 24/9 (615-620)

Essential fatty acid (FA) deficiency, which may accompany protein-energy malnutrition CPEM), has been associated with impaired inflammatory reactions. We evaluated this relationship by analysing FA profiles and delayed cutaneous hypersensitivity in 20 malnourished elderly non-cancer patients and in 20 age matched control patients. As indicated by serum cholesterol and serum triglycerides, the lipid levels were decreased by about one-third in the subjects with PEM. In comparison with the controls, there was a reduction in the omega3 FA (e.g. eicosapentanoate) in total serum lipids (mg l-1) and serum phospholipids (%) of 40% and 47%, respectively. Reductions in serum omega6 FA (e.g. linoleate and arachidonate) levels corresponded to the drop in total FA concentrations (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished patients. The magnitude of the skin reaction was positively correlated (P < 0.05) to the concentrations of eicosapentanoate in serum lipids and serum phospholipids, as well as to the linoieate concentration in total serum lipids. Six of the malnourished patients took part in a nutritional intervention programme for 3 months. In parallel with an improvement in the nutritional status there was a 35% increase (P < 0.05) in the total omega3 FA serum concentration. Negative skin tests became positive and the median skin induration enlarged threefold (P < 0.05). Thus, deficiency of omega3 FA might be one factor contributing to cutaneous anergy in elderly malnourished patients.

Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation: A double- blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams

Griffiths C.E.M.; Kang S.; Ellis C.N.; Kim K.J.; Finkel L.J.; Ortiz-Ferrer L.C.; White G.M.; Hamilton T.A.; Voorhees J.J.
Department of Dermatology, Univ. of Michigan Medical Center, 1910 A. Alfred Taubman Health Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0314 USA
Archives of Dermatology (USA), 1995, 131/9 (1037-1044)

Background and Design: The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are

(1) whether irritation causes all or part of the improvement;

(2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and

(3) the effects of long-term treatment on components of the cutaneous immune system.

To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n=32), 0.025% tretinoin (n=35), or vehicle (n=32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area. Results: Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy be tween the two concentrations o