Intense pulsed light effects on the expression of extracellular matrix proteins and transforming growth factor beta-1 in skin dermal fibroblasts cultured within contracted collagen lattices.

BACKGROUND: Emerging clinical evidence suggests that intense pulsed light (IPL) treatment may exert some beneficial effects on photoaged skin. The molecular mechanisms underlying this IPL effect have not been fully elucidated. OBJECTIVE: To examine the effects of IPL irradiation on normal human dermal fibroblasts grown in contracted collagen lattices. METHODS: Human skin fibroblasts cultured in contracted collagen lattices were irradiated with IPL with triple pulses of 7 ms with a pulse interval of 70 ms and fluences of 20, 50, and 75 J/cm(2). Twenty-four hours after the irradiation, cell viability, messenger RNA (mRNA), and protein levels of extracellular matrix proteins (e.g., collagen I, collagen III, and fibronectin) and transforming growth factor beta-1 (TGF-beta1) were evaluated using dye exclusion, real-time reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. RESULTS: A dose-dependent increase in viable cells was demonstrated after the IPL irradiation. There was no significant change in mRNA levels of collagen I and fibronectin. Upregulated expression of collagen III and TGF-beta1 in dermal fibroblasts was verified. CONCLUSIONS: The analytical results presented here provide a potential mechanistic explanation for the mechanism of clinical photorejuvenation effects of IPL that involves the increase of extracellular matrix construction by upregulating the gene expressions of collagen III and TGF-beta1.

Anti-enterovirus 71 activity screening of chinese herbs with anti-infection and inflammation activities.

Antipyretic and toxin-eliminating traditional Chinese herbs are believed to possess antiviral activity. In this study, we screened extracts of 22 herbs for activity against enterovirus 71 (EV71). We found that only extracts of Houttuynia cordata Thunb. could neutralize EV71-induced cytopathic effects in Vero cells. The 50% inhibitory concentration of H. cordata extract for EV71 was 125.92 +/- 27.84 mug/ml. Antiviral screening of herb extracts was also conducted on 3 genotypes of EV71, coxsackievirus A16 and echovirus 9. H. cordata extract had the highest activity against genotype A of EV71. A plaque reduction assay showed that H. cordata extract significantly reduced plaque formation. Viral protein expression, viral RNA synthesis and virus-induced caspase 3 activation were inhibited in the presence of H. cordata extract, suggesting that it affected apoptotic processes in EV71-infected Vero cells by inhibiting viral replication. The antiviral activity of H. cordata extract was greater in cells pretreated with extract than those treated after infection. We conclude that H. cordata extract has antiviral activity, and it offers a potential to develop a new anti-EV71 agent.

Early congenital syphilis and erythema multiforme-like bullous targetoid lesions in a 1-day-old newborn: detection of Treponema pallidum genomic DNA from the targetoid plaque using nested polymerase chain reaction.

A 1-day-old male newborn was born with respiratory distress, low birth weight, hepatosplenomegaly, and bullous targetoid skin lesions over the face, back, buttocks, and extremities. A diagnosis of early congenital syphilis was made based on a treponemal serologic test. Pathologic examination of the skin lesion showed scattered dyskeratotic cells in the epidermis and interface dermatitis consistent with erythema multiforme. No spirochete could be found in the skin sections staining with Warthin-Starry stain. Using nested polymerase chain reaction, treponemal genomic DNA fragments encoding DNA polymerase I were detected.

Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71.

Viruses have been known to subvert the anti-apoptotic pathways of the host cell in order to delay apoptosis. However, the mechanisms utilized by enterovirus 71 (EV71) to mediate anti-apoptotic activity remained undetermined. We observed that EV71 infection induced an early activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/ERK signaling pathways. The activity of GSK3beta, a downstream target of these pathways, was negatively regulated by the activation of both MAPK/ERK and PI3K/Akt. The phosphorylation of GSK3 could be inhibited by treatment with the specific inhibitors of MAPK/ERK and PI3K/Akt. Other Akt downstream targets, BAD, caspase-9 and the Forkhead transcription factor (FKHR), were not phosphorylated during the course of infection by EV71. We further demonstrated that infection by UV-irradiated, inactivated virus triggered early Akt activation but was insufficient to trigger late Akt activation. These data suggest that with the phosphorylation of MAPK/ERK and PI3K/Akt the subsequent inactivation of GSK3beta is utilized by EV71 as a potential mechanism to delay host cell apoptosis.

Clinicopathologic features of skin reactions to temporary tattoos and analysis of possible causes.

BACKGROUND: Recently, temporary paint-on tattoos have become increasingly popular as a safe alternative to permanent tattoos in Asia and other regions. The most common dye for such temporary tattoos is henna, a vegetable dye. Henna is considered to possess low allergenicity because the incidence of allergic contact dermatitis to henna has rarely been reported. However, recently, allergic reactions to henna used in temporary tattoos have been reported frequently. OBSERVATIONS: Ten patients developed inflamed skin eruptions after receiving temporary paint-on tattoos in either Thailand or Indonesia. The 6 patients who were patch tested all exhibited moderate to strong positive reactions to p-phenylenediamine (1% in petrolatum). Four of the 6 patients were then tested with commercial black henna obtained from Thailand, and all 4 had strong positive reactions. A skin biopsy specimen showed lichenoid dermatitis. Mass spectrometry analysis of commercial black henna for molecular weight revealed a major peak at the mass-charge ratio of 108.1, which corresponds to the molecular weight of p-phenylenediamine. CONCLUSIONS: The most likely causative agent for the lichenoid reaction associated with use of commercial black henna for temporary tattooing, currently popular in Southeast Asia, is p-phenylenediamine. With the increased popularity of temporary paint-on tattoos, clinicians should be aware of the possible associated complications.

Effects of UVR and UVR-induced cytokines on production of extracellular matrix proteins and proteases by dermal fibroblasts cultured in collagen gels%.

Synthesis of extracellular matrix (ECM) proteins and their degradation by matrix metalloproteinases (MMP) are part of the dermal remodeling resulting from chronic exposure of skin to ultraviolet radiation (UVR). We have compared two alternative mechanisms for these responses, namely, a direct mechanism in which UV-B or UV-A is absorbed by fibroblasts and an indirect mechanism in which cytokines, produced in skin in response to UVR, stimulate production of the ECM proteins and MMP. These studies were carried out on human dermal fibroblasts grown in contracted, free-floating 9 day old collagen gels as a dermal equivalent. Synthesis of tropoelastin, collagen, fibrillin, MMP-1, -2, -3 and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were measured. Tropoelastin, collagen and fibrillin levels were stable between days 4 and 10, and MMP and TIMP decreased by day 10. Neither UV-B (2.5-50 mJ/cm2) nor UV-A (2-12 J/cm2) altered synthesis of ECM proteins, but UV-A increased MMP-1 and -3 production. Tropoelastin synthesis increased in response to transforming growth factor-beta1 (5 ng/mL) treatment. Both interleukin-1beta and tumor necrosis factor-alpha (10 ng/mL) decreased fibrillin messenger RNA levels but increased MMP-1, -3 and -9 synthesis markedly. Collagen synthesis was not modulated by UV-B, UV-A or cytokine treatment. These results indicate that certain cytokines may have greater effects on production of ECM proteins and MMP than absorption of UV-B and UV-A by fibroblasts grown in dermal equivalents and suggest that the former pathway may play a role in the dermal remodeling in photoaged skin.

Alternative therapy for autosensitization dermatitis.

During outdoor activities, Dendrocnide meyeniana can induce severe acute dermatitis, which usually needs topical or systemic corticosteroids, and oral antihistamine to alleviate associated symptoms such as exudation, pruritus or burning sensation. In this paper we report a 14-year-old male, with autosensitization dermatitis caused by Dendrocnide meyeniana, who had erythematous papules accompanied by itching and stinging sensations over left inner elbow first and then extended to the trunk and limbs. Based on the theory of traditional Chinese medicine (TCM) and pharmacological studies, the combined formula of Xiao-feng-san (XFS) and Huang-lian-jie-du-tang (HLJDT) was prescribed in the form of concentrated herbal extracts per oral. Remission of skin lesions and the accompanied symptoms was observed after treatment using the TCM formula for 7 days. Follow-up of the patient showed no relapse. We therefore conclude that TCM herbs may provide an alternative treatment for autosensitization dermatitis caused by Dendrocnide meyeniana.

Clinical assessment of patients with recalcitrant psoriasis in a randomized, observer-blind, vehicle-controlled trial using indigo naturalis.

OBJECTIVE: To evaluate the efficacy and safety of treatment with indigo naturalis in patients with recalcitrant plaque-type psoriasis. DESIGN: Randomized, observer-blind, vehicle-controlled, intrapatient comparison study. SETTING: Ambulatory department of a hospital. PARTICIPANTS: Forty-two outpatients with chronic plaque psoriasis were enrolled in the study from May 1, 2004, to April 30, 2005. INTERVENTION: The patients applied either indigo naturalis ointment or vehicle ointment topically to each of 2 bilaterally symmetrical psoriatic plaque lesions for 12 weeks (depending on the date of enrollment in the study). MAIN OUTCOME MEASURES: The outcomes were assessed using the following criteria: the sum of erythema, scaling, and induration scores and the clearing percentage of the target plaque lesion assessed by 2 blinded observers. RESULTS: Significant reductions in the sum of scaling, erythema, and induration scores (P < .001) (mean score, 6.3 after indigo naturalis treatment vs 12.8 in control subjects) and plaque area percentage (P < .001) (mean percentage, 38.5% after indigo naturalis treatment vs 90% in controls) were achieved with topical application of indigo naturalis ointment. Approximately 31 of 42 patients (74%) experienced clearance or near clearance of their psoriasis in the indigo ointment-treated lesion. CONCLUSION: Topical indigo naturalis ointment was a novel, safe, and effective therapy for plaque-type psoriasis.

The efficacy and safety of topically applied indigo naturalis ointment in patients with plaque-type psoriasis.

BACKGROUND: It has been reported in the Chinese literature that indigo naturalis exhibits potential antipsoriatic effects in systemic therapy. OBJECTIVE: To evaluate the efficacy and safety of topically applied indigo naturalis on treating plaque-type psoriasis and to analyze the histological change in skin tissues. METHODS: Fourteen patients with chronic plaque psoriasis were enrolled. The patients were topically applied with either indigo naturalis ointment or vehicle ointment on contralateral skin lesions daily for 8 weeks. Efficacy was evaluated on the basis of the clinical scores, including induration, scaling, erythema and clearing percentage. At the end of treatment, skin punch biopsies were taken and prepared for the immunohistochemical analysis. RESULTS: A significant reduction in clinical scores was achieved with topically applied indigo naturalis ointment. Analysis of biopsies showed a marked improvement of skin histology. The expressions of proliferating marker Ki-67 and inflammatory marker CD3 were decreased, but the differentiation marker such as filaggrin was increased in the epidermis after indigo naturalis ointment treatment. CONCLUSIONS: The results suggest that topical application of indigo naturalis ointment may be a novel, safe and effective therapy for psoriasis that is mediated, at least in part, by modulating the proliferation and differentiation of keratinocytes in epidermis, as well as by inhibiting the infiltration of T lymphocytes and therefore the subsequent inflammatory reactions in psoriatic lesions.

Successful treatment of pediatric psoriasis with Indigo naturalis composite ointment.

The treatment of psoriasis in children is still an intractable problem and demands a long-term therapy with prolonged efficacy that is free from serious adverse events. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis.

Efficacy and safety of topically applied tacrolimus ointment in patients with moderate to severe atopic dermatitis.

BACKGROUND: Tacrolimus is a T-cell-selective cytokine inhibitor. The topical formulation was specifically developed for treating inflammatory skin diseases, including atopic dermatitis (AD). The purpose of this study was to evaluate the efficacy and safety of topically applied tacrolimus ointment (Protopic) in treating Taiwanese patients with moderate to severe AD. METHODS: This was an open-labeled, non-comparative, single-center study. Enrolled patients applied Protopic twice daily for up to 4 weeks. Efficacy was evaluated on the basis of the physician's global evaluation of clinical response (PG). Other evaluations included the Eczema Area and Severity Index and the percentage of body surface area; the total score for clinical signs was used for evaluating the efficacy. A safety assessment was based on adverse events reported by patients or observed by the physician. Blood was sampled for the evaluation of tacrolimus levels. RESULTS: In total, 30 patients (16 pediatric and 14 adult patients) with moderate to severe AD were enrolled in this study. At the end of treatment, the PG was 92.3% for the pediatric group and 100% for the adult group. Other efficacy evaluations also showed significant improvement. Two patients had detectable blood tacrolimus concentrations. Skin itching and burning on the application site was a common but temporary side effect. No significant adverse events related to Protopic were observed. CONCLUSION: The results of the study suggest that Protopic ointment may be a safe and effective therapy for treating patients at least 2 years of age with moderate to severe AD.

Intense pulsed light for the treatment of refractory melasma in Asian persons.

BACKGROUND: Patients with dermal or mixed-type melasmas are often refractory to various treatments. Intense pulsed light has been used to treat melanocytic lesions with promising results. OBJECTIVE: The purpose of this study was to clarify the effectiveness of intense pulsed light for refractory melasma in Asian persons. METHODS: Seventeen patients were treated with intense pulsed light, during four sessions at 4-week intervals. The patients were also given 4% hydroquinone cream and broad-spectrum sunscreens to prevent and treat postinflammatory hyperpigmentation. Sixteen patients in the control group were treated with hydroquinone cream and sunscreens. The treatment efficacy was evaluated using reflectance spectrophotometer and patient satisfaction questionnaire. RESULTS: Patients in the intense pulsed light group achieved an average of 39.8% improvement in relative melanin index, compared to 11.6% improvement in the control group (p<0.05) at Week 16. Six (35%) patients in the intense pulsed light group had more than 50% improvement, compared to two (14%) patients in the control group. Two patients in the intense pulsed light group, however, experienced transient postinflammatory hyperpigmentation, and partial repigmentation was noted 24 weeks after the last treatment session. CONCLUSION: Intense pulsed light is a safe and effective treatment for refractory melasma in Asian persons, with minimal side effects. Further treatment sessions are required for maintenance therapy.