Chronically sun-damaged melanomas express low levels of nuclear glutathione-S-transferase-π: an epidemiological and clinicopathological study in Italy.

The detoxifying enzyme glutathione-s-transferase pi (GST-π) is present in keratinocytes and melanocytes and exerts a protective role against tumour progression. Melanomas close to melanocytic naevus remnants occur less frequently on sun-exposed areas, whereas solar dermal elastosis, hallmark of chronic sun-damage, characterise melanomas on sun-exposed skin. We evaluated the expression of GST-π in 113 melanomas associated to melanocytic naevus remnants or to solar dermal elastosis, classified according to clinical characteristics, history of sun exposure, histological subtypes and AJCC staging. Chronically sun-damaged melanomas, identified by moderate-severe solar dermal elastosis, showed a lower nuclear GST-π expression and a higher thickness than those related to melanocytic naevus remnants (p < 0.03). Multivariate logistic regression analysis demonstrated that male gender and chronic sun-exposure are independent risk factors significantly associated to melanomas localised on the trunk (OR = 3.36, 95% CI: 1.31-8.65; OR = 5.97, 95% CI: 1.71-20.87). If confirmed on a larger series, lower expression of nuclear GST-π in melanoma cells could represent a possible marker of chronically sun-damaged melanoma pathogenesis.

Synthesis of heterocycle-based analogs of resveratrol and their antitumor and vasorelaxing properties.

New resveratrol (RES) analogs were developed by replacing the aromatic 'core' of our initial naphthalene-based RES analogs with pseudo-heterocyclic (salicylaldoxime) or heterocyclic (benzofuran, quinoline, and benzothiazole) scaffolds. The resulting analogs were tested for their antiproliferative and vasorelaxing effect, two typical properties shown by RES. Some of the new compounds confirmed strong antiproliferative activities, comparable to that previously found with the most active naphthalene-based analog. In particular, 3-(3,5-dihydroxyphenyl)-7-hydroxyquinoline exhibited the most potent antiproliferative effect (IC50=17.4 microM). In vascular assays, the highest levels of potency (pIC50=4.92) and efficacy (Emax=88.2%) were obtained with 2-(3,5-dihydroxyphenyl)-6-hydroxybenzothiazole. A conformational analysis of these compounds indicated that the antiproliferative activity on MDA-MB-231 cancer cells can be correlated to a common sterical profile of the most active compounds and, in particular, to the spatial arrangement of the three phenolic groups. Furthermore, the vasorelaxing properties showed a good correlation with the electronic properties measured through the electrostatic molecular potential (ESP).

Treatment of folliculitis with monochromatic excimer light (308 nm).

BACKGROUND/AIMS: 308-nm excimer light has been reported to be safe and effective in the treatment of chronic skin diseases. The aim of the study was to prove the efficacy of 308-nm monochromatic excimer light in the treatment of recalcitrant and antibiotic-resistant folliculitis. METHODS: Eight patients affected with folliculitis were enrolled and treated twice weekly with the 308-nm excimer light. The follow-up was 12 weeks from the end of the treatment. RESULTS: A mean number of 13 sessions (range 10-20) was performed with increasing dosage according to the patient's photo-type and response. Remission, in terms of number and infiltration of papulopustular elements, was achieved in all patients after 4-16 therapeutic sessions. At the end of the follow-up period, recurrence of folliculitis was observed in 2 patients. CONCLUSIONS: These results suggest that the 308-nm excimer light is a valid therapeutic option for the treatment of resistant forms of folliculitis especially in difficult-to-treat areas.

Monoaryl-substituted salicylaldoximes as ligands for estrogen receptor beta.

Salicylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place of the typical phenolic A ring that is characteristic of most estrogen receptor (ER) ligands. Monoaryl-substituted salicylaldoximes were obtained by replacing the phenol moiety (ring A) of the ERbeta pharmacophore with the pseudocycle A' ring, which has previously been shown to behave as a bioequivalent of phenols in nonselective ER ligands. In this series, small substituents (CH 3, CN, Cl) were introduced into the central phenyl scaffold. An efficient sequential halogen-selective double cross-coupling reaction was developed for the synthesis of the methyl-substituted ER ligand. The measured ERbeta affinity proved to be very sensitive to the effect of central core substituents. The binding affinities of the compounds herein reported were in good agreement with the results of computational docking analysis. The chloro-substituted derivative showed the highest beta affinity and selectivity, and it also proved to be an ERbeta partial agonist with an EC 50 of 11 nM.

Clobetasol propionate foam 0.05% as a novel topical formulation for plaque-type and scalp psoriasis.

OBJECTIVES: To establish the efficacy of clobetasol propionate foam 0.05% in patients with plaque-type psoriasis and scalp psoriasis. METHODS: We conducted an open-label study on 24 patients. Twelve patients affected by plaque-type psoriasis (group 1) and 12 patients with scalp psoriasis (group 2) applied clobetasol propionate foam 0.05% twice daily for 4 weeks. RESULTS: Clobetasol propionate foam 0.05% led to a reduction of the disease severity. After 2 weeks the PASI score decreased from 7.5 at baseline to 2.5 (range: 0.8-4.6, SD: 1.1) in group 1 and from 5.7 to 1.7 (range: 0.2-4.8, SD: 1.1) in group 2. At week 4, the mean PASI was 2 (range: 0.6-4, SD: 1) and 1.1 (range: 0.2-2.2, SD: 0.6) in groups 1 and 2, respectively. In particular, at week 2, 83.3% of patients with plaque psoriasis and 75% with scalp psoriasis achieved an improvement of the PASI score from baseline> or =50% (PASI-50). At week 4, 91.6% of patients from group 1 and 100% from group 2 achieved or maintained PASI-50, while 41.6% in group 1 and 58.3% in group 2 demonstrated a further improvement, reaching PASI-75. CONCLUSION: The rapidity of effect and the good safety profile suggest a role for clobetasol propionate foam 0.05% in the management of both plaque-type and scalp psoriasis.

IRIS: methodological assessment of psychopathological disease in a cohort of hirsute women.

BACKGROUND: Hirsutism in females can be a source of considerable psychological distress and a threat to female identity. The aim of our study was to evaluate a possible relationship between facial, total body hair involvement and physical, mental and social well-being during 12 months of follow-up and treatment. Both objective and subjective methods of evaluating hirsutism were used: the Ferriman-Gallwey (FG) scoring method and the questionnaires General Health Questionnaire (GHQ)-12, Polycystic Ovary Syndrome Questionnaire (PCOSQ) and SF-12. METHODS: The total of 469 female patients (mean age 27.61±7.63 years) was enrolled in 27 Italian centers participating in this study. Higher total body score was correlated to significant emotional discomfort. The correlation between the FG total body score, the facial score and physical/mental health was found to be significant in all the patients assessed by SF-12 questionnaire. The ongoing reduction of GHQ-12 score was found for the facial FG score at the first follow-up (T0-T1 period) and at the second one (T0-T2). No relationship was found between T1 and T2. At both 6 (T1) and 12 months (T2) follow-up an increase of PCOSQ Score (psychological improvement) was accompanied by a concomitant reduction of the FG Score (reduction of hirsutism). Physical health assessed by SF-12 questionnaire does not change at both 6- and 12-month follow-up, but mental health decreased at both T1 and T2. RESULTS: The clinical improvement was achieved at 6 months regardless on treatment used and it was maintained for the next six-month follow-up. The clinical outcome could be assessed both by FG Score both through questionnaires administrated to each patient with hirsutism. CONCLUSIONS: For the evaluation of psychopathological discomfort the most appropriate questionnaire was GHQ-12, because of it major sensitivity to identify the psychological discomfort in the hirsutism.

Synthesis of a resveratrol analogue with high ceramide-mediated proapoptotic activity on human breast cancer cells.

Resveratrol, a natural product with a stilbene structure, exerts profound proapoptotic activity in human cancer cells, by triggering the accumulation of ceramide, a bioactive sphingolipid. We studied the biological effects of seven methoxylated and/or naphthalene-based resveratrol analogues and compared these compounds with resveratrol with the objective to identify an analogue with higher ceramide-mediated proapoptotic activity relative to resveratrol. Here we show that the compound with three hydroxyls and a naphthalene ring is the most effective in triggering apoptosis coupled to the induction of endogenous ceramide in human cancer cells.

Tazarotene as alternative topical treatment for onychomycosis.

BACKGROUND: Distal and lateral onychomycoses are the most frequent forms of onychomycosis, causing subungual hyperkeratosis that usually limits local penetration of antimycotic drugs. Tazarotene exerts anti-inflammatory and immune-modulating activities toward both infective agents and damaged keratinocytes. Given the well-documented efficacy of tazarotene on hyperkeratotic nail psoriasis, we investigated its therapeutic use in onychomycosis. PATIENTS AND METHODS: We designed a preliminary open clinical trial in patients affected by distal and lateral subungual onychomycosis of the toenails and verified the fungistatic activity of tazarotene in vitro. Fifteen patients were treated with topical tazarotene 0.1% gel once per day for 12 weeks. Mycological cultures and potassium hydroxide stains of nail samples were performed at the beginning and at the end of the study. Treatment was considered effective when clinical healing and negative mycological culture were obtained. Onycholysis, nail bed discoloration, and subungual hyperkeratosis were measured using standardized methodologies and analyzed by means of Mann-Whitney test and analysis of variance. Fungistatic activity of tazarotene was evaluated by disk diffusion assay. RESULTS: Six patients (40%) reached a mycological cure on target nail samples already after 4 weeks of treatment. Complete clinical healing and negative cultures were reached in all patients at week 12, with a significant improvement of all clinical parameters of the infected nails. Disk diffusion assay after 48 hours of incubation with tazarotene solution showed a central area of inhibition in all examined fungal cultures. CONCLUSION: Our results documented a good clinical outcome using topical tazarotene 0.1% gel in distal and lateral subungual onychomycosis and its fungistatic activity of tazarotene in vitro. The majority of patients appeared cured at a 6-month follow-up. The efficacy and safety of tazarotene must be confirmed on a larger number of patients, although already documented in nail psoriasis patients often affected by onychomycosis.