Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis.

BACKGROUND: Seborrhoeic keratoses (SKs) are very common benign epidermal lesions without malignant potential. Ultraviolet radiation, old age and viruses are well-known risk factors for disease development. However, the pathomechanisms of SK are not fully understood. OBJECTIVES: To detect and characterize the genes that are involved in the pathogenesis of SK. METHODS: We performed a gene expression study using paired lesional and nonlesional skin samples from patients with SK. RESULTS: We identified and validated 19 differentially expressed genes in SK. Of these 19 genes, we focused on p63 transcription factor, which plays a pivotal role in epidermal development by regulating its transcriptional programme. We found by immunofluorescence that the expression of ΔNp63α, the most abundantly expressed p63 isoform, was significantly increased in SK as compared with normal skin. Moreover, siRNA-mediated knockdown of ΔNp63 led to the downregulation of 11 genes, including a member of the tensin family TNS4. Chromatin immunoprecipitation assay revealed that TNS4 was a target gene of p63. CONCLUSIONS: We identified upregulated genes in SK using genome-wide cDNA microarray and elucidated the functional contribution of p63 to the disease transcriptome by gene-silencing assay. Taken together, these data may provide a novel insight into the molecular basis of these benign skin lesions.

Acute exposure of human skin to ultraviolet or infrared radiation or heat stimuli increases mast cell numbers and tryptase expression in human skin in vivo.

BACKGROUND: Mast cells are key effector cells in diverse immunological and pathological processes. It is still unclear why there are more mast cells at peripheral and sun-exposed skin sites than at sun-protected sites. OBJECTIVES: To investigate changes in mast cell numbers associated with natural ageing and photoageing, and to observe the effects of ultraviolet (UV) and infrared (IR) radiation and heat on the prevalence of mast cells and tryptase expression in human skin in vivo. METHODS: Sun-exposed and sun-protected skin samples were taken from individuals in four different age groups. UV, IR or heat-treated buttock skin of young volunteers was also obtained. Mast cells were quantified by immunohistochemical staining of mast cell-specific tryptase and chymase. The expression of tryptase was determined by Western blotting. RESULTS: Both sun-exposed and sun-protected skin showed a gradual decrease in total mast cells (MC(Total)) number with ageing. The number of mast cells in sun-exposed skin was significantly higher than that in sun-protected skin. After UV irradiation (2 minimal erythema doses), MC(Total) and mast cells expressing tryptase and chymase were significantly increased at 24 and 48 h postirradiation. After IR irradiation (3 minimal heating doses) and heat treatment (43 degrees C for 90 min), MC(Total) reached peak induction at 8 and 48 h after stimulation, respectively. Tryptase expression was also clearly upregulated by UV, IR and heat. CONCLUSIONS: Our data demonstrate that mast cell numbers decreased with ageing in human skin. Also, mast cells may be activated and recruited by UV, IR and heat. These findings should further our understanding of the reason for the high prevalence of mast cells at peripheral sun-exposed skin sites.

Effects of 12-O-tetradecanoyl-phorbol-13-acetate [corrected] and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged human keratinocytes.

Skin aging may be divided into photoaging and intrinsic aging. The purpose of this study was to investigate the effects of 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged skin, compared with young skin. Keratinocytes were taken from newborns, young adults in their twenties, and from the forearm and thigh of volunteers in their fifties and seventies. Interleukin-1alpha and -6, and interleukin-1 receptor antagonist, c-fos and c-myc were measured after cultured keratinocytes had been treated with 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate. There has been no report concerning the dependence of cytokine production by sodium lauryl sulfate upon photoaging and intrinsic aging. This study also involves the first investigation of the effects of aging on c-myc expression by 12-O-tetradecanoyl-phorbol-13-acetate treatment. Cytokine production decreased markedly with age. These results suggest the progressive decline of cellular function with age. The ratio of cytokine production in the irritant-treated group compared with that in the control group showed a different pattern in photoaging and intrinsic aging. With the significant difference between photoaging and intrinsic aging, T/C ratio decreased in interleukin-1alpha and interleukin-1 receptor antagonist upon aging, whereas it increased in interleukin-6. S/C ratio was uniquely elevated on photoaged skin in the 50 y age group. It is suggested that photoaged skin shows an exaggerated reaction to surfactant. Compared with the control, c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes decreased with age in the thigh, but increased in the photoaged skin of forearm. The increased c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes could be relevant for the predisposition of photoaged keratinocytes to malignant transformation.

Ultraviolet B irradiation-enhanced interleukin (IL)-6 production and mRNA expression are mediated by IL-1 alpha in cultured human keratinocytes.

Ultraviolet (UV) B radiation may trigger cutaneous inflammatory responses by directly inducing epidermal keratinocytes to elaborate specific cytokines such as interleukin (IL-1) and IL-6. Because IL-1 is a potent inducer of IL-6, one may speculate that the release of IL-6 by keratinocytes after UV exposure is mediated via the release of IL-1 in an autocrine or paracrine manner. We demonstrated that UVB irradiation upregulated IL-1 alpha mRNA at a lower dose (15 mJ/cm2) and then downregulated IL-1 alpha mRNA expression at high doses (30-40 mJ/cm2). The kinetic profile of IL-1alpha mRNA expression showed a biphasic response, with the early increase by 1 h after UV exposure and the secondary increase at 6 h after UV. On the other hand, the expression of IL-6 mRNA was increased with increasing doses of UVB (0-45 m/J/cm2) and showed a single peak at 6 h post UV. These results may indicate that UVB radiation could regulate the expression of IL-1alpha and IL-6 mRNA in keratinocytes by different mechanisms. Our data show that anti-human IL-1alpha antibody inhibits UV-induced IL-6 production and mRNA expression in cultured keratinocytes. The addition of recombinant IL-1alpha to the medium increased IL-6 synthesis and augmented IL-6 production and mRNA expression in cultured human keratinocytes by UVB irradiation. These results support the hypothesis that UVB irradiation-enhanced IL-6 production and mRNA expression may be mediated by IL-1alpha.

Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo.

This is a comprehensive study of the changes in major antioxidant enzymes and antioxidant molecules during intrinsic aging and photoaging processes in the epidermis and dermis of human skin in vivo. We show that the activities of superoxide dismutase and glutathione peroxidase are not changed during these processes in human skin in vivo. Interestingly, the activity of catalase was significantly increased in the epidermis of photoaged (163%) and naturally aged (118%) skin (n = 9), but it was significantly lower in the dermis of photoaged (67% of the young skin level) and naturally aged (55%) skin compared with young (n = 7) skin. The activity of glutathione reductase was significantly higher (121%) in naturally aged epidermis. The concentration of alpha-tocopherol was significantly lower in the epidermis of photoaged (56% of young skin level) and aged (61%) skin, but this was not found to be the case in the dermis. Ascorbic acid levels were lower in both epidermis (69% and 61%) and dermis (63% and 70%) of photoaged and naturally aged skin, respectively. Gluta thione concentrations were also lower. Uric acid did not show any significant changes. Our results suggest that the components of the antioxidant defense system in human skin are probably regulated in a complex manner during the intrinsic aging and photoaging processes.

Ultraviolet radiation increases tropoelastin mRNA expression in the epidermis of human skin in vivo.

Photoaged skin contains elastotic materials in the upper reticular dermis. This phenomenon is commonly known as solar elastosis. Little is known about the mechanisms leading to the accumulation of elastotic materials in photoaged skin, however. In this study, it was demonstrated that ultraviolet irradiation induced tropoelastin mRNA expression in the keratinocytes of human skin in vivo and also in cultured human keratinocytes by in situ hybridization and reverse transcriptase polymerase chain reaction. It was also shown by northern blot analysis (n = 5) that there were increased tropoelastin mRNA levels in the forearm (sun-exposed) skin of elderly persons, compared with upper-inner arm (sun-protected) skin of the same individuals. As demonstrated by in situ hybridization compared to sun-protected skin (upper-inner arm) (n = 5), tropoelastin mRNA expression in photoaged skin was higher in keratinocytes as well as in fibroblasts. Therefore, our results suggest that keratinocytes are another source of tropoelastin production after acute and chronic ultraviolet irradiation in human skin in vivo.

Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.

To the best of our knowledge, no study has been conducted to date to directly compare the collagen metabolism of photoaged and naturally aged human skin. In this study, we compared collagen synthesis, matrix metalloproteinase-1 levels, and gelatinase activity of sun-exposed and sun-protected skin of both young and old subjects. Using northern blot analysis, immunohistochemical stain, and Western blot analysis, we demonstrated that the levels of procollagen type I mRNA and protein in photoaged and naturally aged human skin in vivo are significantly lower than those of young skin. Furthermore, we demonstrated, by northern blot analysis, that the procollagen alpha1(I) mRNA expression of photoaged skin is much greater than that of sun-protected skin in the same individual. In situ hybridization and immunohistochemical stain were used to show that the expression of type I procollagen mRNA and protein in the fibroblasts of photoaged skin is greater than for naturally aged skin. In addition, it was found, by Western blot analysis using protein extracted from the dermal tissues, that the level of procollagen type I protein in photoaged skin is lower than that of naturally aged skin. The level of matrix metalloproteinase-1 protein and the activity of matrix metalloproteinase-2 were higher in the dermis of photoaged skin than in naturally aged skin. Our results suggest that the natural aging process decreases collagen synthesis and increases the expression of matrix metalloproteinases, whereas photoaging results in an increase of collagen synthesis and greater matrix metalloproteinase expression in human skin in vivo. Thus, the balance between collagen synthesis and degradation leading to collagen deficiency is different in photoaged and naturally aged skin.

A study of skin responses to follow-up, rechallenge and combined effects of irritants using non-invasive measurements.

Irritant contact dermatitis is a common clinical problem. Primary irritation can be easily recognized, but cumulative irritation by daily exposure is hard to be diagnosed and the condition may fail to be clear even away from work. The mechanism of irritant dermatitis produced by repeated or combined exposure to clinical or subclinical doses of irritants is still poorly understood. In order to find out whether the subclinical doses of irritants affect each other by repeated or combined exposure according to their concentrations, non-invasive measurements, transepidermal water loss and laser Doppler flowmetry were used. Sodium lauryl sulfate, sodium hydroxide and benzalkonium chloride were serially diluted and patch-tested with large Finn chambers on Scanpor tape on the back of normal human volunteers and responses were followed up for 7 days. Twice repeated exposure with subclinical doses of irritants at 1 day intervals were also performed. Repeated daily applications for 5 days with subclinical doses of single or premixed irritants were performed to know the combined irritating effect. The irritant response was well correlated to the concentration of the irritants. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites. Twice-repeated exposure of subclinical doses of irritants increased skin irritancy when measured by transepidermal water loss and laser Doppler flowmetry. Some correlation and some discrepancies were observed between different evaluation methods in combined and repeated application tests with irritants of subclinical doses. Responses of skin irritancy induced by subclinical doses showed somewhat different pattern from that given strong irritants.(ABSTRACT TRUNCATED AT 250 WORDS)

Comprehensive outlook of in vitro tests for assessing skin irritancy as alternatives to Draize tests.

In vitro alternative methods have been verified for the possibility to assess cutaneous irritancy because humans cannot be direct initial experimental subjects and animal experimentation could be forbidden in the near future. Many kinds of cell cytotoxicity assays have been tried, revealing their own advantages and limitations. Cell function-based tests have been used less frequently than cytotoxicity assays. Three-dimensional culture systems are promising because they are closer to the actual in vivo skin, and some of them are commercialized nowadays. The ultimate objective of in vitro irritancy tests, which is the high degree of correlation with human in vivo test results, has been accomplished in many experimental settings. Before applying these in vitro methods we must consider several points, including cell sources, irritant characteristics, exposure time, endpoint of experiment, extrinsic factors affecting irritation, etc. In vitro skin irritancy tests have been developed continuously, and in the future they could assume a heavy responsibility of estimating the irritancy in human skin in vivo.

Differences between fibroblasts cultured from oral mucosa and normal skin: implication to wound healing.

It is generally agreed that oral mucosa heals faster with less scar than skin does, and hypertrophic scar or keloid is very rare in the oral cavity. Fibroblasts are thought to play an important role in wound healing and scar formation, whose control is mediated by growth factors. We have studied whether there are any differences in the cellular behavior of fibroblasts between oral mucosa and skin, and in their response to growth factors. Oral mucosal fibroblasts proliferated slightly more than dermal fibroblasts on average. Dermal fibroblasts in collagen gel possessed greater contraction potency than oral mucosa fibroblasts, irrespective of the presence of growth factors; however, oral mucosa fibroblasts showed an earlier collagen gel contraction with or without TGF-beta1. There were no differences in basal collagen synthetic rate between dermal and oral mucosal fibroblasts, while the latter synthesized more collagen than dermal fibroblasts when they were stimulated with TGF-beta1. Our study showed that oral mucosal fibroblasts and dermal fibroblasts had selective differences in cellular behavior and in their responses to growth factors, which seems to contribute to the differences in wound healing.

Change of glutathione S-transferases in the skin by ultraviolet B irradiation.

Glutathione S-transferases (GSTs) may play an important role in protecting skin from ultraviolet radiation (UVR). However, the study on the response of GST to UVR is limited at present. We have examined the effects of a single exposure to ultraviolet B (UVB) radiation on GST in cultured human keratinocytes and the epidermis of SKH/hr-1 hairless mice. We have also investigated the changes of skin GST by chronic irradiation of UVB on the hairless mice. Significant decreases in GST activities in vitro and in vivo were observed at 24 h after 30 and 50 mJ/cm2 UVB irradiation. Chronic UVB exposure also caused decrease in GST activities of the skin tissue. However, any changes in mRNA expression or protein amount of GST have not been observed by Northern blot analysis and Western blot analysis after 30 mJ/cm2 UVB irradiation in cultured human keratinocytes, which suggests that mRNA expression and protein amount of GST are not affected by UVB. These results suggest that UVB irradiation results in inhibitory effect on GST activity in the skin.

Regulations of collagen synthesis by ascorbic acid, transforming growth factor-beta and interferon-gamma in human dermal fibroblasts cultured in three-dimensional collagen gel are photoaging- and aging-independent.

Decreased collagen synthesis and loss of responsiveness to growth factors are well known phenomena in in vivo or in vitro aged cells. Ascorbic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To investigate the responsiveness of fibroblasts with regard to the photoaging and aging process, we examined the effect of ascorbic acid, TGF-beta, and IFN-gamma on collagen synthesis in dermal fibroblasts from three newborn foreskins (1 day old) and in both exposed and unexposed skin fibroblasts from 4 old individuals (60-76 years old) cultured in monolayer and in collagen gel. We demonstrated that basal levels of collagen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibroblasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated in a photoaging- and aging-dependent manner, collagen synthesis by ascorbic acid in collagen gel, and by TGF-beta and IFN-gamma in both monolayer culture and collagen gel were regulated in a photoaging- and aging-independent manner. In monolayer culture, however, the responsiveness to ascorbic acid in newborn fibroblasts was greater than in photoaged and aged fibroblasts. Our results suggest that there are differences in collagen synthesis between photoaged and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synthesis are downregulated in a photoaging- or aging-dependent manner.

Growth related secretion and production of GM-CSF by epithelial cell line.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor that supports the clonal development of normal granulocyte-macrophage progenitors. Especially in the skin, GM-CSF from keratinocytes may be a critical factor in the melanogenesis of the skin. In addition, GM-CSF is thought to play an important role in impaired wound healing. However, little is known regarding the synthesis and secretion of GM-CSF by keratinocytes of the skin. This investigation evaluated the effects of cell density on the production of GM-CSF by keratinocytes and the changes in the cell cycle. Interestingly, GM-CSF protein secretions and mRNA expressions were highly elevated in sub-confluent HaCat cells, and decreased in confluent state. In particular, GM-CSF production decreased in a density-dependent manner. We also found that the percentage of cells in the S phase of the cell cycle decreased markedly from 50 to 10% when HaCat cells reached a confluent state. These results showed that GM-CSF synthesis and secretion by HaCat cells increases when cells are rapidly proliferating such as in the wound healing process. Thus, it might be said that GM-CSF produced by proliferating keratinocytes possibly contributes to wound healing and melanogenesis at the site of injury.

Reconstruction of human hard-palate mucosal epithelium on de-epidermized dermis.

Artificial hard-palate mucosa equivalents were reconstructed using keratinocytes derived from normal human hard-palate and de-epidermized dermis. Reconstructed hard-palate mucosal epithelium formed in three-dimensional culture was compared to native hard-palate mucosal epithelium and reconstructed oral buccal mucosal epithelium with regard to keratin expression. Artificial hard-palate mucosal epithelium reconstructed in medium with delipidized serum showed a differentiation pattern similar to that of hard-palate epithelium in vivo. The present study also confirmed that keratinocytes derived from hard-palate mucosa are intrinsically different from those of nonkeratinizing oral surfaces.

Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color.

BACKGROUND: Severe wrinkles and pigmentary changes of the exposed skin indicate substantial damage due to UV radiation. Many investigators believe that the principal manifestation of photodamage in Asians is pigmentary change rather than wrinkles. However, to our knowledge, no well-designed study has investigated the characteristics of cutaneous photodamage in Asian skin. OBJECTIVE: To access the severity of wrinkles and dyspigmentation in Koreans exposed to sun and who smoked. METHODS: We developed new photographic scales for grading wrinkles and dyspigmentation in 407 Koreans to assess the severity of the wrinkles and dyspigmentation. We interviewed subjects to determine cumulative sun exposure and smoking history, and measured the skin color of individual subjects. RESULTS: Our photographic scales provided a reliable evaluation of photodamage severity in Koreans. The pattern of wrinkling in both sexes is similar, but women tended to have more severe wrinkles (prevalence odds ratio, 3.7). However, the pattern of dyspigmentation differed between the sexes. Seborrheic keratosis is the major pigmentary lesion in men, whereas hyperpigmented macules are the prominent features in women. Cigarette smoking is an independent risk factor for wrinkles, but not for dyspigmentation, in Koreans, and causes additive detrimental effects to wrinkles induced by aging and sun exposure. The constitutive skin color did not show any correlation with wrinkles or dyspigmentation. However, facultative pigmentation (sun exposure index) may reflect lifetime sun exposure, and it shows a good correlation with wrinkles in Koreans. CONCLUSION: Wrinkling is a major feature of photoaging in Koreans, as are pigmentary changes; smoking, sun exposure, and female sex are independent risk factors for wrinkles.

Overexpression of HSP70 prevents ultraviolet B-induced apoptosis of a human melanoma cell line.

The heat shock response is a highly conserved reaction common to all cells and organisms. It has been reported that hyperthermic treatment can induce the expression of the heat shock protein (HSP) and can protect cells from ultraviolet (UV) B radiation. In this study, we evaluated the effects of induced HSP70 on resistance to UV radiation. G361 amelanotic human melanoma cells were irradiated with increasing doses of UVB. UVB irradiation caused apoptotic cell death in these cells. Following transfection with MFG.hsp70.puro plasmid, the expression of HSP70 was determined. Compared to control vector-transfected cells, hsp70-transfected cells showed significantly elevated levels of HSP70 and were highly resistant to UVB irradiation. In order to investigate the effects of HSP70 on the apoptotic pathway, the changes in caspase-3 and PARP were analyzed. Following UVB irradiation, activation of caspase-3 and cleavage of PARP were observed in control vector-transfected cells, and the changes in these molecules were inhibited in the hsp70-transfected cells. These results suggest that UVB-induced apoptosis of melanoma cells is accompanied by caspase-3 activation and PARP cleavage, which can be prevented by an overexpression of HSP70.

Human oral buccal mucosa reconstructed on dermal substrates: a model for oral epithelial differentiation.

To develop a model for the study of oral epithelial differentiation, we reconstructed artificial buccal mucosa equivalents using keratinocytes and fibroblasts or de-epidermized dermis derived from non-cornifying buccal mucosa. The buccal mucosa equivalents reconstructed in this way showed a morphology closely mimicking that of their in vivo counterparts. There was no formation of horny layers and granular layers. The expression of various differentiation markers such as K13, involucrin and loricrin was consistent with that of the in vivo state, and indicative of the hyperproliferative state. We also demonstrated that the differentiation of oral epithelial cells was influenced by the de-epidermized dermis and subepithelial fibroblasts. The epidermis of buccal mucosa equivalents seemed to be less sensitive to retinoic acid than that of the skin. The effects of calcipotriol on the buccal mucosa equivalent and the skin epidermis were different. These results suggest that the pharmacological effects of retinoic acid and calcipotriol on the buccal mucosa are different from those on the skin. A useful model system for studies of oral keratinocyte differentiation and pharmacological research could be based on these artificial buccal mucosa equivalents.

Evaluation of skin blood flow by laser Doppler flowmetry.

Laser Doppler flowmetry is an excellent noninvasive technique for the measurement of cutaneous microcirculation. The list of applications of laser Doppler flowmetry in dermatology is long. It can be applied to monitor inflammation caused by various drugs, chemicals, and allergens related to blood flow. To measure certain inflammatory reactions a combination of other bioengineering measurements is desirable. Flaps can be monitored, and burn depth measured by laser Doppler flowmetry. Through blood flow measurement, the pathophysiology of various skin diseases can be verified and certain treatments can be partially monitored. Although it is not as directly applicable to daily clinical practice, except in a few cases, laser Doppler flowmetry is a very useful technique in various kinds of dermatologic research.

Botulinum toxin treatment for a compensatory hyperhidrosis subsequent to an upper thoracic sympathectomy.

BACKGROUND: Compensatory hyperhidrosis is the commonest complication of sympathectomy, but there's no known effective treatment. METHODS: Botulinum toxin type A (a total dose of 300 MU, 1.0 MU/cm(2)) was used successfully to treat a 68-year-old male with a 5-year history of compensatory hyperhidrosis of the anterior chest following thoracic sympathectomy for palmar hyperhidrosis. RESULTS: The hyperhidrosis resolved for 8 months without systemic side effects. CONCLUSION: Intracutaneous injection of botulinum toxin is a fast, safe, effective and well-accepted approach for treatment of compensatory hyperhidrosis.

Successful treatment of dandruff with 1.5% ciclopirox olamine shampoo in Korea.

BACKGROUND: Dandruff is a chronic scalp condition characterized by scaling. The common causative agent is now accepted to be the lipophilic yeast Malassezia furfur. Ketoconazole, a highly effective antifungal agent against M. furfur has been used for the treatment of dandruff. AIM: To determine whether a 1.5% ciclopirox olamine shampoo is as effective as a 2% ketoconazole shampoo for the treatment of mild to moderate dandruff. METHODS: A total of 64 patients, with mild to moderate dandruff, participated in the study. The study consisted of three consecutive phases: a 2-week washout period, a 4-week treatment period and a 2-week post-treatment period. Patients were randomized equally to either the 1.5% ciclopirox olamine shampoo or 2% ketoconazole shampoo. An overall dandruff score was calculated using an area of dandruff involvement score and a severity score. Patients evaluated the presence of pruritus and also reported a global evaluation of efficacy. RESULTS: In all, 57 patients successfully completed all three phases. The overall dandruff score declined progressively throughout the treatment period for both shampoos. A slight increase in pruritus was observed in the ciclopirox olamine treatment group during the post-treatment phase. Regarding global self-assessment of efficacy, both treatment groups were pleased with their scalp condition following treatment. CONCLUSION: Ciclopirox olamine shampoo appears to offer an effective, safe and easy to use treatment for mild to moderate dandruff.