Melatonin Prevents UVB-Induced Skin Photoaging by Inhibiting Oxidative Damage and MMP Expression through JNK/AP-1 Signaling Pathway in Human Dermal Fibroblasts.

Exposure to ultraviolet (UV) irradiation causes damage to the skin and induces photoaging. UV irradiation stimulates production of reactive oxygen/nitrogen species, which results in activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) in fibroblasts. MAPKs are responsible for activation of activator protein-1 (AP-1), which subsequently upregulates expression of matrix metalloproteinases (MMPs). Melatonin is a potent free radical scavenger which is known to have photoprotective effects. The aim of this study is to investigate the underlying molecular mechanisms for the photoprotective effects of melatonin in UVB-irradiated primary human dermal fibroblasts (HDFs) in terms of EGFR activation, oxidative/nitrosative damage, JNK/AP-1 activation, MMP activities, and the levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and type I procollagen (PIP-C). In this study, HDFs were pretreated with 1 µM of melatonin and then irradiated with 0.1 J/cm2 of UVB. Changes in the molecules were analyzed at different time points. Melatonin inhibited UVB-induced oxidative/nitrosative stress damage by reducing malondialdehyde, the ratio of oxidized/reduced glutathione, and nitrotyrosine. Melatonin downregulated UV-induced activation of EGFR and the JNK/AP-1 signaling pathway. UVB-induced activities of MMP-1 and MMP-3 were decreased and levels of TIMP-1 and PIP-C were increased by melatonin. These findings suggest that melatonin can protect against the adverse effects of UVB radiation by inhibiting MMP-1 and MMP-3 activity and increasing TIMP-1 and PIP-C levels, probably through the suppression of oxidative/nitrosative damage, EGFR, and JNK/AP-1 activation in HDFs.

Melatonin attenuates the detrimental effects of UVA irradiation in human dermal fibroblasts by suppressing oxidative damage and MAPK/AP-1 signal pathway in vitro.

BACKGROUND: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures. OBJECTIVES: In this study, we investigated the effects of melatonin on UVA-irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time-dependent manner which have not been clearly elucidated yet. METHODS: To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub-cytotoxic dosage (20 J/cm2 ) after pretreatment with melatonin (1 µmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points. RESULTS: Our results clearly show that melatonin decreases UVA-induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP-1 signal transduction pathway and production of matrix metalloproteinases in a time-dependent manner. CONCLUSION: Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.

Effects of the 810-nm diode laser on hair and on the biophysical properties of skin.

INTRODUCTION: Laser therapy is clinically effective in hair removal; however, despite the development of various strategies, laser procedures still present a risk of adverse effects due to the overheating of the skin. OBJECTIVE: To investigate the effects of 810-nm diode laser treatment on hair and on the biophysical properties of skin by using various non-invasive techniques on various parameters, including hair analysis, surface color changes, integrity of skin barrier, sebum production rate and pH level. METHODS: In this randomized, right-left comparison study, 35 women with axillary hair received single-session diode laser therapy. Hair analysis and biophysical properties of the skin were assessed before treatment and at weeks 2, 4 and 6 after the therapy. RESULTS: Hair density and thicknesses statistically significantly decreased after the first post-treatment evaluation. Regarding comparison of the biophysical properties of the skin, there was no statistically significant difference in the assessments, except for the increase determined during the second week in the erythema index in the laser-treated areas. CONCLUSION: The findings of this study showed that the diode laser can perform a significant reduction in the hair amount without significant epidermal damage, at least for a short period.

Glycolic acid peels versus amino fruit acid peels for acne.

INTRODUCTION: Chemical exfoliation resulting in the reduction of keratotic plugs serves as a second-line treatment used as an adjunct to anti-acne agents. This study was designed to compare the therapeutic effects of glycolic acid (GA) peels and amino fruit acid (AFA) peels in patients with acne vulgaris. METHODS: In this single-blind, randomized, right-left comparison study, 24 patients received 12 serial peels (GA and AFA, at concentrations from the lowest to the highest) on the two halves of the face at 2-week intervals for 6 months. In addition, cutaneous tolerability assessments during the applications and the patient preference test between both peeling methods at the end of the study were performed. RESULTS: There was a statistically significant decrease in the number of non-inflamed lesions with GA following the first month and with AFA following the second month (p < 0.05). The decrease in the number of inflamed lesions was statistically significant with GA at the end of the fifth and sixth months and with AFA only at the end of the fifth month (p < 0.05). When the two applications were compared with each other, there was not a statistically significant difference in terms of non-inflamed and inflamed lesions (p > 0.05). During the application, it was observed that AFA peels caused fewer problems than GA peels did. AFA concentrations were increased more rapidly and more sessions were performed at the highest concentration of AFA. CONCLUSION: Based on the results of this study, we can state that both GA and AFA peels are efficacious for comedonal acne. And, compared to a GA peel, an AFA peel is less irritating and better tolerated.

Glycolic acid peels versus amino fruit acid peels in the treatment of melasma.

BACKGROUND: Chemical peels are becoming more popular as a treatment modality for melasma. OBJECTIVE: To compare the therapeutic effects of glycolic acid (GA) peels and amino fruit acid (AFA) peels in patients with melasma. METHODS: In this single-blind, randomized right-left comparison study, patients received 12 serial peels on the two halves of the face at 2-week intervals for 6 months. Clinical evaluation based on the modified Melasma Area and Severity Index (MASI) scores was performed at baseline and at 3 and 6 months. RESULTS: The modified MASI scores at 3 and 6 months in both application areas decreased significantly from baseline (p<.05). When the two applications were compared with each other, there was no statistically significant difference between GA and AFA in terms of regression of melasma (p>.05). During the application, it was observed that AFA peels caused fewer problems than GA peels did. CONCLUSIONS: Based on the results of this study, GA and AFA peels for melasma therapy were efficacious, but the AFA peel was found to be less irritating and was better tolerated.

Quantification of female pattern hair loss: a study in a Turkish population.

Studies dealing with the relationship between the clinical staging of female pattern hair loss (FPHL) and quantitative measurements of hair parameters are limited. This study was performed to quantify Turkish women's hair characteristics in FPHL, to assess the relationship between clinical presentations of FPHL with hair density and anagen hair ratio and to compare the differences in hair parameters between FPHL and normal women, using epiluminescence microscopy combined with digital image analysis (Trichoscan). Hair density and anagen hair ratio measurements of 39 patients with FPHL were evaluated according to clinical stages and compared with those of 31 healthy volunteers. The results of digital image analysis were compared with the results of visual counting using the photomacrographs of the same images. Mid-scalp hair density and anagen ratio of the patients were detected to be significantly lower than those of the controls. The visual counting detected significant differences among the hair densities of all groups including controls, Ludwig I, and Ludwig II/III groups, while digital image analysis revealed a significant difference only between controls and Ludwig II/III groups. Thus digital image analysis was found to underestimate hair density, and the amount of underestimation demonstrated a positive correlation with hair density. In conclusion, diminished hair density seems to be the main sign in the clinical diagnosis of hair loss, although digital image analysis was found to be less competent than visual counting in detecting hair density. Thus, the increase in hair density in the assessment of various treatment modality effects may be underestimated by digital image analysis.

Effect of ultraviolet B radiation on the absorption characteristics of various intraocular lenses.

BACKGROUND: The aim of this study was to determine the effect of ultraviolet B (UVB) exposure on UV filters of various intraocular lenses (IOLs). METHODS: Eight samples each of the hydrophobic acrylic, hydrophilic acrylic and silicone IOLs were used. Four IOLs of each type was selected randomly as the control group while the remaining four IOLs of each type were exposed to a UVB dose of 1.4 J/cm(2) (2.40 mW/cm(2)) for 9.45 min, two times with a 4-week interval. IOLs were evaluated for any sign of opacification under microscope weekly. After a follow-up period of 16 weeks, spectrometry for UV filter absorption rates, scanning electron microscopy for deposit formation and energy dispersive X-ray analysis for elemental composition were performed for all IOLs, and findings of the control group IOLs were compared with those of the UVB-exposed IOLs. All these procedures were done at the Department of Ophthalmology, Faculty of Medicine, Dokuz Eylul University. RESULTS: All the IOLs were free of any opacification during the follow-up period. Spectrometric analysis of their UV filters revealed a change in absorption rates in the hydrophilic acrylic and silicone IOLs compared to the control IOLs of the same type. Only the hydrophobic acrylic IOLs preserved the same UV absorption curve after UVB exposure. CONCLUSION: The pathogenesis of IOL opacification is still undetermined. Some reports claimed that the UV light was the responsible factor. Our experimental study revealed that high doses of UVB did not cause any opacification though they impaired the function of UV filters of the hydrophilic acrylic and silicone IOLs.

Circulated activated platelets and increased platelet reactivity in patients with Behçet's disease.

Behçet's disease (BD) is a multisystem disorder. Venous as well as arterial thrombosis is a common complication of BD but exact pathogenetic mechanism of the thrombotic tendency is not well known. This study aimed to evaluate circulating activated platelets and platelet reactivity in Behçet's patients. Twenty-two Behçet's patients (4 female, 18 male; mean age 38.6 +/- 10.9 years) and 20 control subjects (8 female, 12 male; mean age 38.8 +/- 9.4 years) were included. Those patients who had hypertension, hyperlipidemia, peripheral or coronary artery disease, hepatic or renal function abnormality, and who were using aspirin and other platelet-active drugs were excluded. Platelet activity and reactivity to adenosine diphosphate (ADP) were measured by whole blood flow cytometry. We assessed markers of platelet degranulation (P-selectin; CD62P) and the activated glycoprotein IIb/IIIa receptor (PAC1 binding to fibrinogen binding site) before and after stimulation with ADP. Platelet P-selectin expression was not significantly different between patients and control subjects both at baseline (p=0.420) and after stimulation (p=0.56). Baseline (p=0.001) and ADP-stimulated (p=0.003) PAC1 binding was significantly higher in Behçet's patients than in the control group. Clinical activity has no effect on P-selectin expression and PAC1 binding. There is evidence of platelet activity and hyperreactivity in patients with BD and this may contribute to a prothrombotic state. In addition to aspirin, other antiplatelet drugs may be useful in the prevention and treatment of thrombosis in Behçet's patients.

Naproxen-induced lichen planus: report of 55 cases.

BACKGROUND: Clinical and histopathological differential diagnosis is usually impossible in drug-induced lichen planus (LP) and idiopathic LP. Naproxen is a nonsteroidal anti-inflammatory drug, which is widely used for its analgesic, antipyretic and anti-inflammatory effects. To the best of our knowledge, two case reports on naproxen-induced LP have been reported. METHODS: Fifty-five patients with LP, and a history of naproxen intake before their eruption, were investigated. RESULTS: Twenty-five patients (45.5%) had a history of naproxen intake prior to their eruption without any other medication. Twelve patients (21.8%) had a history of simultaneous use of naproxen with other drugs that were reported as inducers of LP. Eighteen patients (32.7%) had given a history of using naproxen together with drugs that had not been previously reported as inducers of LP. Moreover, in 42 patients, eruptive-type LP development after naproxen intake, is an interesting observation. New lesions were not observed after the cessation of naproxen intake in any of the patients. CONCLUSION: Naproxen might be accepted as an important inducer for LP, especially for the eruptive form.

Peeling skin syndrome.

Peeling skin syndrome is a rare disease characterized by widespread painless peeling of the skin. To date, several cases have been described with different clinical features called peeling skin syndrome. Previous reports describe two types (type A and type B) of peeling skin syndrome, both of which show generalized desquamation, sparing palms and soles. We report a 23-year old man who has been classified as neither type A nor type B, and whose history, clinical features and histopathological findings led to a diagnosis of peeling skin syndrome. In addition, the desquamation pattern in our patient was different from that of both types because our case's palms and soles were involved too.

Task-based learning programme for clinical years of medical education.

CONTEXT: Task-based learning (TBL) is an educational strategy recommended for the later years of the medical education programme. The TBL programme was adopted for clinical years in the 2000-2001 academic year in Dokuz Eylul University School of Medicine (DEUSM). OBJECTIVE: The aim of this paper is to describe the TBL programme of DEUSM. METHODS: DEUSM outlined 50 clinical tasks for fourth-year students and 37 for fifth-year students. The tasks were grouped into four and five blocks. Interdisciplinary practicals, lectures and patient visits were organised in each task's schedule. The tasks were the focus of learning and each discipline contributed its own learning opportunities to the attached tasks. Formative and summative methods were used to evaluate the programme. CONCLUSION: Based on the experience and feedback provided by the students and trainers, the authors considered TBL an applicable and advisable approach for the clinical years of medical education.

Comparison of the effects of pulsed dye laser, pulsed dye laser + salicylic acid, and clobetasole propionate + salicylic acid on psoriatic plaques.

BACKGROUND: Studies show that pulsed dye laser (PDL) has some clinical benefits on psoriasis with a low clearance rate. In addition, it has been suggested that applying keratolytics before treatment might be helpful in PDL therapy. Topical corticosteroids remain the most commonly prescribed agents for psoriasis. OBJECTIVE: This study was designed to compare the efficacy of the PDL treatment with that of PDL treatment after salicylic acid on psoriatic plaques. The other goal of this study was to compare the efficacy of the PDL treatment with that of clobetasol propionate treatment. METHODS: Twenty-two patients with chronic, stable psoriatic plaques that involved less than 20% of their body were included in the study. Three similar-appearing psoriasis plaques in these patients were selected. Whereas the first plaque received only PDL, the second plaque received PDL after salicylic acid, and the third plaque received clobetasol propionate ointment and salicylic acid. Evaluation of the study plaques was carried out by the modified Psoriasis Area and Severity Index (mPASI) score and by measuring the area of the plaques. RESULTS: Of the 21 patients, 19 completed the study. Although the decrease in mPASI scores was determined to be maximum for clobetasol propionate + salicylic acid-treated plaques and minimum for only PDL-treated plaques, the decrease was statistically significant in all groups when compared with baseline (p < .003). At the 3- and 6-week evaluations, there was a statistically significant difference between clobetasol propionate + salicylic acid-treated plaques and the two PDL-treated plaques (p < .003); however, the difference observed at the 9-, 12-, and 15-week evaluations was statistically significant only between clobetasol propionate + salicylic acid-treated plaques and PDL-treated plaques (p < .003). When the baseline and 15-week evaluations were compared, there was no statistically significant increase in the mean lesion areas of clobetasol propionate + salicylic acid-treated psoriatic plaques (p > .003), but there was a statistically significant increase in the mean lesion areas of two PDL-treated psoriatic plaques (p < .003). CONCLUSION: The results of this study showed that the effect of PDL could be increased when salicylic acid was added to treatment, although there was no statistically significant difference between both treatment protocols. However, clobetasol propionate + salicylic acid treatment is more effective than both PDL and PDL + salicylic acid treatment.

Effects of calcipotriol cream and ointment, clobetasol cream and ointment and tretinoin cream on the erythemogenicity of UVB.

Various studies have shown the blocking effects of topical agents on UVB penetration, which can be used in combination with phototherapy. In this study, the photoprotective effects of 0.005% calcipotriol, 0.05% clobetasol-17-propionate, and 0.1% tretinoin, which can be used in combination with broad-band UVB, were investigated in an in vivo test. In a study group of 20 patients, phototests were performed to determine minimal erythema doses (MED) and the tests were repeated with thin (0.1 cc/25 cm2) and thick (0.3 cc/25 cm2) calcipotriol, clobetasol-17-propionate, and tretinoin in cream forms and sunscreen. After determining the MED, the test was repeated in another 20 patients with thin and thick calcipotriol and clobetasol-17-propionate in both cream and ointment forms and sunscreen. MED was increased with thin and thick applications of all agents. Moreover, the photoprotective effects of each agent increased with their thick applications compared with thin ones. The application of calcipotriol cream and ointment, clobetasol cream and ointment, and tretinoin cream, all of which can block UVB, is not recommended just before phototherapy.

Is there any association between hepatitis G virus (HGV), other hepatitis viruses (HBV, HCV) and Behçet's disease?

Infectious agents, especially viruses, have been implicated in the pathogenesis of Behçet's disease (BD). The aim of this study was to determine whether BD is associated with hepatitis viruses. In this study, the serological markers of hepatitis (HBsAg, anti-HBs, anti-HBc and anti-HCV) and viral nucleic acid (HGV-RNA) were studied in the sera of 35 patients, all of whom fulfilled the diagnostic criteria of the International Study Group for BD, and the results were compared with those of 36 healthy controls. The prevalences of HBsAg, anti-HBs, anti-HBc in BD patients were 2.9%, 45.7%, and 31.4%, respectively, which were not significantly different from those in healthy controls. None of the subjects in either group were found to be positive for anti-HCV. HGV-RNA was detected in two patients with BD and in none of the healthy controls. In conclusion, BD does not seem to be associated with hepatitis viral infections including hepatitis B, C, or G.

Effects of topical petrolatum and salicylic acid upon skin photoreaction to UVA.

Various agents which can be used in combination can also interfere with phototherapy. In this study, the effects of topical petrolatum and 20% salicylic acid in petrolatum upon skin photoreaction to UVA were investigated, in an in vivo test. Minimal phototoxic dose (MPD) test was performed on 31 volunteers and the test was repeated with thin (0.1 cc/25 cm(2)) petrolatum, thick (0.3 cc/25 cm(2)) petrolatum, thin 20% salicylic acid in petrolatum, thick 20% salicylic acid in petrolatum and sunscreen. The effect of each agent on MPD was investigated. MPD was increased with thin and thick applications of all agents. Also, MPD was increased with 20% salicylic acid in petrolatum when compared with pure petrolatum, in the same thickness. The application of petrolatum and salicylic acid in petrolatum just before PUVA therapy is not recommended because of their blocking effects.

An unusual cutaneous lesion as the presenting sign of spinal dysraphism in a preterm infant.

We present a preterm female infant with an unusual vascular nevus on the lumbosacral and gluteal regions. Our clinical diagnosis was probable twin nevus, with a blanched nevus adjacent to a telangiectatic nevus, later complicated by ulceration. Ultrasonography and magnetic resonance imaging of the lumbosacral region revealed that her conus medullaris level was at L4 and the spinal cord was tethered by an intraspinal lipoma, without evidence of a hemangioma. We could not find any literature reporting the association of twin nevus with spinal dysraphism.

Phototoxic effects of topical azelaic acid, benzoyl peroxide and adapalene were not detected when applied immediately before UVB to normal skin.

The enhancing effects on UVB erythema of topical agents applied on sun exposed areas are important due to their increased sunburn risk. Since the lesions in acne vulgaris are seen primarily on the face, the effects of topical agents used in acne treatment on the erythemogenicity of UVB is important. The aim of the present study was to examine whether azelaic acid cream, benzoyl peroxide gel, adapalene gel have the enhancing effects on UVB erythema which are widely used in the topical treatment of acne vulgaris. The minimal erythema dose (MED) was determined with phototest in 30 volunteers and the test was repeated with thin (0.1 cc/25 cm(2)) and thick (0.3 cc/25 cm(2)) azelaic acid cream, benzoyl peroxide gel, adapalene gel. The effects of each agent on MED was determined after 24 hours. MEDs of UVB were unaffected by azelaic acid cream, benzoyl peroxide gel and adapalene gel when applied immediately before irradiation. According to our results azelaic acid, benzoyl peroxide and adapalene do not seem to have enhancing effects on UVB erythema and thus increased sunburn risk.