Steven Nisticò

Lecithin microemulsions for the topical administration of ketoprofen: percutaneous adsorption through human skin and in vivo human skin tolerability

The potential application of highly biocompatible o/w microemulsions as topical drug carrier systems for the percutaneous delivery of anti-inflammatory drugs, i.e. ketoprofen, was investigated. Microemulsions were made up of triglycerides as oil phase, a mixture of lecithin and n-butanol as a surfactant/co-surfactant system and an aqueous solution as the external phase. To evaluate the percutaneous enhancing effect of oleic acid, this compound was used as a component of some o/w microemulsions. The topical carrier potentialities of lecithin-based o/w microemulsions were compared with respect to conventional formulations, i.e. a w/o emulsion, a o/w emulsion and a gel. Physicochemical characterisation of microemulsions was carried out by light scattering and zeta potential analyses. Microemulsions showed mean droplet size < 35 nm and a negative zeta potential, that is -39.5 mV for the oleic acid-lecithin microemulsion and -19.7 mV for the lecithin-based microemulsion. The percutaneous adsorption of the various topical formulations was evaluated through healthy adult human skin, which was obtained from abdominal reduction surgery. Ketoprofen-loaded microemulsions showed an enhanced permeation through human skin with respect to conventional formulations. No significant percutaneous enhancer effect was observed for ketoprofen-loaded oleic acid-lecithin microemulsions. The human skin tolerability of various microemulsion formulations was evaluated on human volunteers. Microemulsions showed a good human skin tolerability.

A 308-nm monochromatic excimer light in the treatment of palmoplantar psoriasis.

Background  Various reports have shown the efficacy of narrow‐band UVB (311–313 nm) and excimer laser (308 nm) in the treatment of psoriasis.

Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study

Vitiligo is an acquired depigmentation disorder affecting 1–4% of the worlds population. Conventional therapies include steroids, photosensitive topical agents, surgical treatments, and phototherapy. The aim of the study was to evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a monotherapy and in combination with khellin 4% ointment in vitiligo. Forty‐height patients (36 male and 12 female) affected with vitiligo were enrolled in this open prospective study. Patients were selected and divided into three groups: group I included 16 patients treated with MEL 308 nm once‐weekly and oral vitamin E; group II included 16 patients treated with MEL 308 nm once‐weekly combined with khellin 4% ointment (MEL‐K) and oral vitamin E; group III (control group) included 16 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. Group I (MEL‐group) showed a moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%) patients. Group II (MEL‐K group) presented moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%) patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The clinical response achieved in group I and II was higher compared with group III (control group) without showing significant differences. MEL 308 nm, alone and/or combined with khellin 4% offered encouraging results and it may be considered a valid therapeutic option worthy of consideration in the treatment of vitiligo.

Safety and efficacy study on etanercept in patients with plaque psoriasis

instructed to continue pimecrolimus ointment once weekly for the next 6 weeks. None had relapsed at 4-week follow-up. Our preliminary data indicate that pimecrolimus 1% cream is highly effective for perianal AD. Notably, we observed relief from clinical symptoms after only 2 weeks of therapy. When pimecrolimus 1% cream has been applied to adults with AD affecting the body, improvement has been observed as early as the first week, with a 72% reduction in severity after 3 weeks. The mechanism of action of pimecrolimus includes the inhibition of signal transduction pathways in T cells and the synthesis of inflammatory cytokines, specifically T-helper (Th) 1 and Th2 type cytokines. Pimecrolimus has also been shown to prevent the release of cytokines, proinflammatory mediators from mast cells, and itch-inducing neuropeptides. It has been shown to be as effective as clobetasol-17-propionate (0Æ05%) when applied under occlusion to psoriatic lesions. Moreover, Thaci et al. demonstrated that occlusive treatment of chronic hand dermatitis with pimecrolimus 1% cream twice daily is effective and safe. Pharmacokinetic studies revealed very low blood levels of pimecrolimus even following occlusive application. One may speculate that an increased rate of percutaneous penetration of pimecrolimus into inflamed intertriginous skin mainly contributed to the high efficacy observed in our investigation. In particular in the management of perianal AD, calcineurin inhibitors appear to be the first real alternative to topical GCS. However, future blinded, randomized, placebo-controlled studies are now warranted to substantiate our results.

Monochromatic excimer light (308 nm) in the treatment of prurigo nodularis.

Three hundred and eight nanometre excimer light has been reported to be safe and effective in the treatment of chronic skin diseases, but the range of potential applications has not been fully explored. Our objective was to assess the efficacy of monochromatic excimer light (MEL) in the treatment of prurigo nodularis (PN). Eleven patients were enrolled in this pilot study. Patients were treated weekly and an average of eight sessions of MEL was given. Follow‐up was 4 months. Partial or complete clinical and histological remission was observed in all patients who completed the study (81%).

Ethanol-induced injury in rat primary cortical astrocytes involves oxidative stress: effect of idebenone.

Ethanol-induced neurological disorders have recently been characterised. Indeed, evidence has been collected indicating that chronic ethanol consumption leads to direct or indirect changes in the viability of central nervous system cells. Here we investigated the role of free radical overproduction in primary cortical rat astroglial cells undergoing chronic treatment with ethanol (100 microM). In particular, exposure of astroglial cell cultures to ethanol for 12 consecutive days produced an increased release of lactic dehydrogenase, a decrease on glutamine synthase activity being both effects accompanied by decrease in astroglial viability as detected by MTT (Thiazolyl Blue) test. These effects were accompanied by an increased formation of malondialdehyde (a marker of lipid peroxidation) and by abnormal formation of heat shock protein, being both effects antagonised by liposomally entrapped idebenone, a non-peptidyl free radical scavenger. Taken together, these results suggest that ethanol-induced injury on astroglial cells are mediated by abnormal formation of free radical species and this may represent a useful approach in the treatment of ethanol-related brain disorders.

EFFICACY OF MONOCHROMATIC EXCIMER LIGHT (308 NM) IN THE TREATMENT OF ATOPIC DERMATITIS IN ADULTS AND CHILDREN

OBJECTIVE To demonstrate the efficacy of light produced by a 308 nm xenon-chloride monochromatic excimer light (MEL) in the treatment of localized lesions of atopic dermatitis (AD) in adults and in children. BACKGROUND DATA The 308-nm excimer light has been reported to be safe and effective in the treatment of chronic skin diseases, although the range of potential applications has not been fully explored. METHODS Twelve adults and six children affected by localized lesions of AD were enrolled in this pilot study and treated with a weekly session of MEL. A range of 6-12 sessions was performed with an increasing dosage according to the patients phototype and response. Follow-up was for 16 wk. RESULTS All patients completed the protocol. At the end of treatment complete remission was observed in 12/18 patients (66.7%), a partial remission in 3/18 (16.7%) and no remission in 3/18 (16.7%). A mean total dose of 21.89 minimal erythemal dose (MED) was performed. Forty-four percent of patients maintained the results achieved at a 16-week follow-up. Treatment was well tolerated overall. CONCLUSIONS MEL can be considered as a valid and safe therapeutic option for the treatment of localized AD in adults and children.

An occlusive dressing containing betamethasone valerate 0.1% for the treatment of prurigo nodularis

Abstract Introduction: Prurigo nodularis is a distressing condition characterized by the presence of multiple nodules associated with intense pruritus. Objective: To assess the clinical efficacy and safety of betamethasone valerate 0.1% tape and a moisturizing itch-relief cream in prurigo nodularis. Methods: Twelve patients were enrolled in this pilot comparison of betamethasone valerate 0.1% tape versus a moisturizing itch-relief cream containing feverfew. The study period was 4 weeks. Clinical evaluation was performed weekly. Results: Eleven subjects completed the 4 weeks of therapy. The mean visual analogue scale (VAS) for pruritus at baseline was 8.75 for both sides of the body. The side treated with betamethasone valerate 0.1% tape showed a higher clinical response (VAS score at week 4: 3.9; p < 0.005) compared with the side treated with moisturizing itch-relief cream (VAS score at week 4: 5.6; p < 0.005). Conclusion: Both treatments were effective. However, the occlusive dressing enhanced the efficacy of the treatment, preventing scratching.

Connexin 26 (GJB2) mutations as a cause of the KID syndrome with hearing loss.

KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea. These channels play a role in the coordinated exchange of molecules and ions occurring in a wide spectrum of cellular activities. In this paper we describe two patients with Cx26 mutations cause cell death by the alteration of protein trafficking, membrane localization and probably interfering with intracellular ion concentrations. We discuss the pathogenesis of both the hearing and skin phenotypes.

Infrared Saliva Analysis of Psoriatic and Diabetic Patients: Similarities in Protein Components

Goal: Psoriasis is a chronic skin disease which is very common in the population and requires frequent clinical and pharmacological treatment. In the following, a study based on Fourier transform infrared spectroscopy analyzing saliva proteomic components in psoriatic patients against diabetic patients and a control group is presented. Clinical analysis showed a prominent amide II band, at around 1545 cm-1, and the composition of the amide I band, at around 1647 cm-1, allowing us to distinguish the infrared salivary signature of psoriatic and diabetic patients from the control group and even from patients with different kinds of psoriasis. Moreover, results highlighted existing differences in the secondary structure composition of proteins between psoriatic and diabetic patients as compared to the control group. In fact, the saliva spectra of the control group and that of the palmoplantar psoriatic patients differ from plaque psoriasis and diabetic patient spectra because of the absence of the amide II band and the presence of different secondary protein-structure conformations.