Stefania Motta

Ceramide composition of the psoriatic scale

This paper investigates the ceramide composition of the psoriatic scale compared with that of normal human SC. A method was optimalized, based on TLC separation followed by densitometry, allowing the provision of good resolution and quantification of ceramide fractions from both normal and pathological specimens. Seven ceramide fractions were isolated and submitted to compositional analysis. The obtained results suggested a revisitation of previous ceramide designation. Therefore a simple classification is suggested, based on grouping ceramides carrying structural similarities under common codes. According to these rules, ceramides were grouped into five classes designated as: (1) Cer[EOS], which contains ester-linked fatty acids, omega-OH fatty acids and sphingosines; (2) Cer[NS], which contains non-OH fatty acids and sphingosines; (3) Cer[NP], which contains non-OH fatty acids and phytosphingosines; (4) Cer[AS], which contains alpha-OH fatty acids and sphingosines; (5) Cer[AP], which contains alpha-OH fatty acids and phytosphingosines. Analysis of ceramides from the psoriatic scale, compared to those from normal human SC, resulted in an impairment of the Cer[EOS] content as well as of the ceramides containing phytosphingosine, with concurrent increase in ceramides containing sphingosine, being the total amount maintained identical. Since one of the suggested pathways for phytosphingosine biosynthesis involves the water addition to the corresponding sphingosine double bond, we can speculate that the observed alteration is due to a deranged water bioavailability, associated with psoriasis.

Content of the different lipid classes in psoriatic scale.

Studies on stratum corneum have demonstrated that interlamellar lipids are functionally involved in the maintenance of barrier function [ 1 ]. In addition, recent investigations have Correlated interlamellar lipid synthesis with the desquamation rate and the mitotic activity, of keratinocytes [2]. The complexity of the functions of the horny layer lipid compartment are strictly related to a constant and well-defined proportion of the different lipid classes as hypothesized in previous reports [3-5]. Psoriasis is characterized by both increased desquamation and keratinocyte hyperproliferation as a consequence of an increased mitotic rate of basal cells [6]. In addition horny layers are deranged, causing an increase in water flux and absorption [7]. Recently, we reported significant variations in the ceramide composition of psoriatic scale compared with normal human stratum corneum [8]. In the present study we determined the relative proportions of the lipid classes present in scales from psoriatic skin and compared them with those in normal human stratum corneum in an attempt to correlate psoriatic barrier alteration with the content and/or relative proportion of each lipid class. Different lipid classes in both normal and psoriatic specimens were analysed by a procedure involving extraction of total lipids, separation of individual classes by thin-layer chromatography and quantification by densitometry. Normal human stratum corneum was obtained by trypsinization of abdominal skin samples obtained during plastic surgery from six subjects (both sexes), Psoriatic scale samples were obtained using tweezers from abdominal lesional areas of ten subjects (all male). Both normal and psoriatic samples were processed for lipid extraction

Clinical management of cutaneous toxicity of anti-EGFR agents

Cutaneous toxicity is the most evident adverse effect of epidermal growth factor receptor (EGFR) inhibitors because of the specific role played by EGFR in skin biophysiology. Dermatological adverse reactions, mainly folliculocentric, have been widely reported in the literature. However, the mechanism of these reactions is not well defined and their management is still a matter of debate. In this paper keratinocyte differentiation, activation and pathways regulating gene expression are reviewed in order to improve the understanding of adverse skin reactions and obtain success in their management. The authors had the opportunity to treat skin reactions induced by cetuximab in a cohort of patients affected by metastatic colorectal carcinoma. The aims of this clinical approach were to control the signs and symptoms of skin toxicity in order to avoid delay in cancer therapy and to use nondrug agents for the treatment of drug-induced skin reactions.

Isolation and Characterization of Multipotent Cells from Human Fetal Dermis

We report that cells from human fetal dermis, termed here multipotent fetal dermal cells, can be isolated with high efficiency by using a nonenzymatic, cell outgrowth method. The resulting cell population was consistent with the definition of mesenchymal stromal cells by the International Society for Cellular Therapy. As multipotent fetal dermal cells proliferate extensively, with no loss of multilineage differentiation potential up to passage 25, they may be an ideal source for cell therapy to repair damaged tissues and organs. Multipotent fetal dermal cells were not recognized as targets by T lymphocytes in vitro, thus supporting their feasibility for allogenic transplantation. Moreover, the expansion protocol did not affect the normal phenotype and karyotype of cells. When compared with adult dermal cells, fetal cells displayed several advantages, including a greater cellular yield after isolation, the ability to proliferate longer, and the retention of differentiation potential. Interestingly, multipotent fetal dermal cells expressed the pluripotency marker SSEA4 (90.56 ± 3.15% fetal vs. 10.5 ± 8.5% adult) and coexpressed mesenchymal and epithelial markers (>80% CD90+/CK18+ cells), coexpression lacking in the adult counterparts isolated under the same conditions. Multipotent fetal dermal cells were able to form capillary structures, as well as differentiate into a simple epithelium in vitro, indicating skin regeneration capabilities.

Neutrons for rafts, rafts for neutrons.

The determination of the structure of membrane rafts is a challenging issue in biology. The selection of membrane components both in the longitudinal and transverse directions plays a major role as it determines the creation of stable or tunable platforms that host interactions with components of the outer environment. We focus here on the possibility to apply neutron scattering to the study of raft mimics. With this aim, we realized two extreme experimental models for the same complex membrane system (phospholipid : cholesterol : ganglioside GM1), involving two of the characteristic components of glycolipid-enriched rafts. One consists of a thick stack of tightly packed membranes, mixed and symmetric in composition, deposited on a silicon wafer and analyzed by neutron diffraction. The other consists of a free floating individual membrane, mixed and asymmetric in composition in the two layers, studied by neutron reflection. We present here results on the ganglioside-cholesterol coupling. Ganglioside GM1 is found to force the redistribution of cholesterol between the two layers of the model membranes. This causes cholesterol exclusion from compositionally symmetric ganglioside-containing membranes, or, alternatively, asymmetric cholesterol enrichment in raft-mimics, where gangliosides reside into the opposite layer.Graphical abstract

Topical preparations and vehicles

Dermatological therapy can be a combination of systemic and topical treatments although topical treatment is often the only therapy prescribed. As a consequence, dermatologists have to be familiar with the use of topical preparations, whether a drug or an active agent is added or not. Tailor-made preparations have undoubtedly a great positive impact on patients but their use is limited by two main factors: the poor confidence of practising dermatologists to prescribe magistral compositions and the difficulty in finding pharmacists capable and willing to provide them. In a recent analysis of compound prescriptions, some mixtures prescribed by dermatologists were questionable either because of the number of active ingredients or the selected concentrations. As a general consideration, the chemical agents that may be applied to the skin for their local effects belong to two categories: drugs non-drugs. The agents of the first category have a selective action in terms of chemical and pharmacological activity on the skin. Antibiotics, antimycotics, corticosteroids, antineoplasties are some examples. They are prepared by pharmaceutical companies according to strict international rules on suitable vehicles and are ready to use. Their use in combination with other ingredients is neither recommendable nor economically worthwhile. The second category is composed of a heterogeneous group of agents which, by exclusion, do not belong to the first. They have mostly a non-selective action, have limited chemical and pharmacological activity and, sometimes, have just a physical action. These locally acting agents include most absorbents, astringents, demulcents, rubefacients, keratolytics and miscellaneous other ingredients used dermatologically. The local treatment of skin disorders also includes the exclusive use of vehicles. Therefore, excluding drugs, topical treatment may be subdivided into: non-specific treatment with bases specific treatment with active agents.

Kidney transplant recipients and sun exposure

Non-melanoma skin cancers induced by solar radiation are the most frequent types of cancers in humans and their incidence is increasing worldwide. Ultraviolet radiation (UV) is a major environmental cause. The individual risk of skin cancer is due both to the total cumulative exposure to UV radiation and to sporadic patterns of sun exposure as during free time. Organ transplant recipients have a relative risk of developing squamous cell carcinoma 100-fold higher than healthy subjects, whereas the risk of developing basal cell carcinoma is increased by 10. Beside the direct effect on keratinocyte DNA, UV radiations have also a negative effect on the local immunosurveillance in the exposed areas and on systemic immunity. Educational programs on sun exposure for organ transplant recipients recommend to limit the time of exposure and to apply sunscreen creams. Sunscreen creams are topical preparations that attenuate the effects of UV radiation on the skin. Recently the safety of sunscreen creams is a matter of discussion because of the toxicological studies performed on chemical filters. The majority of chemical filters absorb through the skin, then into the blood. T-shirts, hats and sunglasses provide full protection from UV rays. Body areas (face, neck, ears and décolleté) exposed to solar radiation can be efficiently protected applying a blend of mineral powders (clays, bentonite, kaolin, montmorillonite) formulated to reflect sunrays. The use of mineral powders as sunscreens is encouraged also for dialysed subjects and for patients with autoimmune diseases.

Influence of topical tretinoin on skin lipid production in vivo

Topical application of tretinoin induces skin changes characterized by erythema, dryness and desquamation. These changes are primarily due to a specific tretinoin action on keratinocyte differentiation and proliferation [1]. Tretinoin added to cultured keratinocytes is able to impair morphological structure and the expression of several markers of terminal differentiation such as filaggrin, loricrin and involucrin [2]. The reduction in the expression of these proteins is considered to be the cause of a reduced and less adhesive horny layer [3]. Interlamellar lipids also play an important role in lamellar cohesion and adhesion in the stratum corneum layers [4]. However, little information is available on the effects of retinoic acid (RA) on interlamellar lipid synthesis [5]. The synthesis of these specific lipids is a part of keratinocyte differentiation [6], so theoretically tretinoin may also affect keratinocyte lipid metabolism. The aim of this study was to verify in vivo whether the topical application of tretinoin induces any modification in lipid production. For this purpose lipids from cyanoacrylate strippings of the horny layer after 21 days tretinoin exposure were analysed and compared with those from a vehicle-treated area of the same subject. Stratum corneum samples were obtained from the volar forearm of ten healthy volunteers, all females (ages ranging from 28 to 35 years), treated with freshly prepared tretinoin (all-trans-RA) 0.05%, glycoalcoholic solution, once a day, Monday to Friday, for a period of 21 days (15 applications). The contralateral forearm was treated with vehicle (propylene glycol/ethanol, 1:1) as control. The clinical score was recorded 2 days after the final application, and transepidermal water loss (TEWL) was measured by means of an evaporimeter (EP1, Servomed, Stockholm, Sweden). Stratum corneum samples were obtained by a single