O. Simonetti

Università Politecnica delle Marche, Italy, DISCO, Faculty Member

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Papers by O. Simonetti

In vitro activity of the lipopeptide derivative (Pal-lys-lys-NH 2 ), alone and in combination with antifungal agents, against clinical isolates of dermatophytes

British Journal of Dermatology, 2009

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Changes of Plasma Lipids and Erythrocyte Membrane Fluidity in Psoriatic Children

Pediatric Research, 1993

Psoriasis has been associated with an abnormal plasma lipid metabolism, and changes of erythrocyt... more Psoriasis has been associated with an abnormal plasma lipid metabolism, and changes of erythrocyte membrane lipid composition and fluidity have been shown in adult patients. To investigate whether the alterations of plasma lipids appear also in pediatric patients, we have studied plasma lipids and lipoproteins in 15 prepubertal children affected by mild-to-moderate psoriasis with respect to healthy controls. The patients showed higher levels of plasma total cholesterol (4.44 + 0.78 versus 4.03 f 0.58 mmol/L), a significant increase of cholesterol associated with HDL (1.39 +. 0.26 versus 1.13 +. 0.28 mmol/ L, p = 0.02), and a significant decrease of the ratio LDL cholesterol to HDL cholesterol (1.73 + 0.6 versus 2.46 2 0.8, p = 0.02). By using fluorescence polarization of 1,6diphenyl-1,3,5-hexatriene, we have shown a significant increase in fluidity in erythrocyte membrane of psoriatic children that was associated with a slight, but not significant, decrease in the cholesterol to protein ratio (422 + 127 versus 503 f 117 nmol/mg). No significant changes of phospholipid fatty acid composition have been shown, in disagreement with previous studies in adult patients. Our results support the relation between childhood psoriasis and plasma lipid changes, which are likely related to the slight compositional changes in erythrocytes. However, the observed abnormalities are expressed differently in children than in adults. (Pediatr Res 33: 506-509, 1993) Abbreviations DPH, 1,6-diphenyl-1,3,5-hexatriene HDL-C, cholesterol associated with high-density lipoprotein LDL-C, cholesterol associated with low-density lipoprotein Pf, fluorescence polarization TC, total cholesterol TG, triglyceride VLDL-C, cholesterol associated with very low-density lipoprotein Psoriasis is a chronic inflammatory skin disease characterized by an accelerated turnover of epidermal cells and an incomplete differentiation in lesional epidermidis. The etiology of psoriasis is unknown, but genetic, metabolic, and immunologic mechanisms have been proposed (1). Various disorders of the plasma lipid and lipoprotein pattern that include an increase in TG in VLDL and a decrease in HDL-C have been shown in adult

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CTACK /CCL27 expression in psoriatic skin and its modification after administration of etanercept

British Journal of Dermatology, 2007

Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokin... more Tumour necrosis factor-alpha upregulates the expression of a cutaneous T cell-attracting chemokine (CTACK/CCL27), that promotes migration of cutaneous lymphocyte-associated antigen-positive lymphocytes into the skin. The role of CTACK/CCL27 in pathogenesis of psoriasis has recently been documented but no data are available at the present time on its modification in psoriatic cutaneous tissue after administration of etanercept. To evaluate modifications of CTACK/CCL27 expression in skin of patients with psoriasis after administration of etanercept and their relation with disease activity. Twenty-two patients with moderate to severe psoriasis underwent clinical, histological and immunohistochemical evaluations of disease activity at baseline and at 12 and 24 weeks after starting treatment with etanercept. All selected patients experienced an improvement of Psoriasis Area and Severity Index (PASI) score (P < 0.001) and Dermatology Life Quality Index score (P < 0.001) during the t...

New Perspectives on Old and New Therapies of Staphylococcal Skin Infections: The Role of Biofilm Targeting in Wound Healing

Antibiotics

Among the most common complications of both chronic wound and surgical sites are staphylococcal s... more Among the most common complications of both chronic wound and surgical sites are staphylococcal skin infections, which slow down the wound healing process due to various virulence factors, including the ability to produce biofilms. Furthermore, staphylococcal skin infections are often caused by methicillin-resistant Staphylococcus aureus (MRSA) and become a therapeutic challenge. The aim of this narrative review is to collect the latest evidence on old and new anti-staphylococcal therapies, assessing their anti-biofilm properties and their effect on skin wound healing. We considered antibiotics, quorum sensing inhibitors, antimicrobial peptides, topical dressings, and antimicrobial photo-dynamic therapy. According to our review of the literature, targeting of biofilm is an important therapeutic choice in acute and chronic infected skin wounds both to overcome antibiotic resistance and to achieve better wound healing.

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In vitro susceptibility of dermatophytes to conventional and alternative antifungal agents

Medical …, 2008

The minimum inhibitory concentrations (MICs), the minimal fungicidal concentrations (MFCs), the f... more The minimum inhibitory concentrations (MICs), the minimal fungicidal concentrations (MFCs), the fungal biomass (FB) and hyphal viability employing the dye 3-4,5 dimethyl-2-thiazolyl-2,5-diphenyl-2H tetrazolium bromide (MTT) were used to compare the in vitro effects of fluconazole (FLU) with those of the Nterminal palmitoyl-lipidated peptide, Pal-Lys-Lys-NH 2 (PAL), and a tea tree oil component, g-Terpinene (TER), against several clinical isolates of Microsporum canis and Trichophyton rubrum. In general, FLU and PAL MICs were significantly lower than those observed with TER, while no differences in the three drugs were found in the MFCs. However, they were from two to 16-times higher than their respective MICs. FB of M. canis treated with either FLU or PAL, but not with TER, was significantly reduced over untreated controls. Only PAL and TER, in a medium-dependent fashion, but not FLU, reduced the FB of T. rubrum. Finally, PAL was found to be significantly more active than FLU at reducing the hyphal viability against both genera of dermatophytes. This study shows that PAL exerts an in vitro activity against dermatophytes at least similar to that observed with FLU and suggests that this compound might be a promising candidate in the treatment of infections due to dermatophytes.

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In vitro activity of the lipopeptide PAL-Lys-Lys-NH2, alone and in combination with antifungal agents, against clinical isolates of Candida spp

by O. Simonetti and C. Silvestri

Peptides, 2011

Candida albicans is known to be the organism most often associated with serious fungal infection,... more Candida albicans is known to be the organism most often associated with serious fungal infection, but other Candida spp. are emerging as clinical pathogens associated with opportunistic infections. Among antimycotic treatments, increasing attention is currently given to anti-infective drugs based upon naturally occurring peptides, such as the short lipopeptide palmitoyl PAL-Lys-Lys-NH2 (PAL). The aim of this study is to evaluate the activity of this peptide compared to the traditional antifungal agents Fluconazole (FLU), amphotericin B (AMB) and caspofungin (CAS) on Candida spp. 24 clinical isolates of Candida spp. were tested against PAL, FLU, AMB and CAS using in vitro susceptibility tests, time killing and checkerboard assay. All of the drugs studied showed good activity against clinical isolates of candida; in particular CAS and AMB which have MICs value lower than PAL and FLU. Moreover we observed synergistic interactions for PAL/FLU (81.25%), PAL/AMB (75%) and particularly for PAL/CAS (87.5). We think that our results are interesting since synergy between PAL and CAS might be useful in clinic trails to treat invasive fungal infections.

Plasma Lipid Changes in Psoriatic Children

by Grazia Bossi and O. Simonetti

Dermatology, 1992

Plasma lipid, lipoprotein and apoprotein concentrations were determined in psoriatic children and... more Plasma lipid, lipoprotein and apoprotein concentrations were determined in psoriatic children and in healthy controls. The plasma total cholesterol (TC) was higher than in controls (p = 0.03). The higher cholesterol levels were explained by an almost significant increase in cholesterol associated with high-density lipoproteins and by the tendency towards higher values of cholesterol associated with low-density lipoproteins and very-low-density lipoproteins. No significant changes of plasma triglycerides were observed. Levels of apoproteins (apo) AI and apo B were not significantly different in psoriatic children; however, the levels of apo B were correlated differently with plasma TC in psoriatic children, and the ratio TC/apo B was significantly increased in patients with respect to the controls, suggesting some differences of plasma lipoprotein lipid/apoprotein relationship in psoriasis.

Hypereosinophilic dermatosis: skin lesions as the only manifestation of the idiopathic hypereosinophilic syndrome?

by Grazia Bossi and O. Simonetti

British Journal of Dermatology, 2000

1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting a... more 1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting and PUVA. J Am Acad Dermatol 1995; 32: 943±8. 2 Kim HY, Kang KY. Epidermal grafts for treatment of stable and progressive vitiligo. J Am Acad Dermatol 1999; 40: 412±7. 3 Jones SK, Darville JM. Transmission of virus particles by cryotherapy and multi-use caustic pencils: a problem to dermatologists? Br J Dermatol 1989; 121: 481±6. 4 Charles CR, Sire DJ. Transmission of papovavirus by cryotherapy applicator. JAMA 1971; 218: 1435.

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Plasma membrane fluidity of keratinocytes of normal and psoriatic skin: A study using fluorescence anisotropy of trimethylammoniumdiphenylhexatriene (TMA-DPH)

Archives of Dermatological Research, 1996

The aim of this study was to investigate p l a s m a m e m b r a n e fluidity in h u m a n kerati... more The aim of this study was to investigate p l a s m a m e m b r a n e fluidity in h u m a n keratinocytes using fluorescence anisotropy of 1,6-diphenyl-l,3,5-hexatriene (DPH) and its cationic derivative 1-[4-(trimethylamino)-phenyl]-6-phenyl-l,3,5-hexatriene (TMA-DPH). Keratinocytes from n o r m a l or psoriatic skin were isolated using trypsin-EDTA or dispase. In keratinocytes isolated from n o r m a l skin, T M A -D P H anisotropy values were higher than those observed using DPH; the difference must be related to the different localization of the two probes. In fact, D P H in whole cells localizes in p l a s m a as well as intracellular m e m b r a n e s , yielding an average value of fluidity, while the cationic derivative T M A -D P H resides in the p l a s m a m e m b r a n e of the whole cells for a sufficient time for anisotropy measurements. Moreover, it has to be considered that p l a s m a m e m b r a n e is more ordered than intracellular m e mbranes. The kinetics of incorporation of T M A -D P H was similar in keratinocytes isolated using trypsin-EDTA and those isolated using; dispase, however, the fluorescence anisotropy values were lower in keratinocytes isolated with dispase (0.260 + 0.01 vs 0.270 + 0.01, p = 0.029). This difference is p r o b a b l y related to modifications of lipid-protein interactions after trypsin treatment. Since no d a m a g e to plasma m e m b r a n e after incubation with dispase seems to have been reported, we decided to use this separation procedure to study p l a s m a m e m b r a n e fluidity in psoriasis, a h u m a n pathological condition characterized by excessive cell proliferation and incomplete differentiation. Lower anisotropy values (0.260 + 0.01 vs 0.270 + 0.01, p = 0.001), indicating an increase in fluidity, were observed O. Simonetti (1~) in keratinocytes isolated f r o m skin of psoriatic patients than in epidermal cells isolated from n o r m a l hum a n skin. We suggest that the m e a s u r e m e n t of fluorescence anisotropy in living cells is a convenient and useful tool to study m e m b r a n e fluidity in h u m a n keratinocytes isolated f r o m n o r m a l and diseased skin. Its application represents a technical advance because plasma m e m b r a n e fluidity can be measured using very limited a m o u n t s of tissue, as obtained from biopsies.

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