Annamaria Offidani

Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions

Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72‐kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP‐2]) and the 92‐kDa gelatinase B/Type IV collagenase (MMP‐9).

Effect of etanercept on insulin sensitivity in nine patients with psoriasis.

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6). In particular, TNF-α causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-α to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.

Vegf is Likely a Key Factor in the Link between Inflammation and Angiogenesis in Psoriasis: Results of an Immunohistochemical Study

Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling. An immunohistochemical study on fifteen cryosections of psoriatic skin was performed using antibodies against VEGF, HIF1-α, CD34, Factor VIII, MMP-2, MMP-9, TIMP-1 and TIMP-2. Psoriatic skin showed a diffuse VEGF positive staining (13.15± 6.6), while no expression was observed in normal epidermis. No or faint HIF-1α immunostaining was detected in healthy skin, while in psoriatic skin HIF-1α was diffusely expressed. A positive correlation between HIF-1α and VEGF was reported in psoriatic skin (r= 0.644; p=0.010). In psoriatic sections CD34 expression was significantly higher in respect to control skin (19.15 ± 12.61 vs 3.0 ± 0.23; p= 0.04), factor VIII immunostaining also demonstrated a significant increased development of the microvasculature in comparison with healthy skin (18.39 ± 8.16 vs 7.4 ± 0.20; p= 0.033). Total MMP-2 expression of healthy skin (30± 2.26) was significantly lower in respect to the MMP-2 psoriatic skin (71.5±4.13; p= 0.0001) and a positive correlation was observed between VEGF and MMP-2 in psoriatic patients (r= 0.688; p= 0.046). In psoriatic skin MMP-9 expression was significantly increased in comparison to control skin (31±3.3 vs 8±6.1; p=0.007). All cases of psoriatic skin tissue showed that TIMP-2 and TIMP-1 expression statistically decreased in psoriatic skin (respectively 11±1.2 and 12±1.5) in comparison with healthy skin (respectively 15±3.2 and 53±3.8; p=0.0001). In conclusion, we observed that VEGF overexpression correlated with HIF-1α and MMP-2 expression, underlining the role of VEGF in psoriasis as a key factor in the link between inflammation and angiogenesis.

RNAIII-Inhibiting Peptide Enhances Healing of Wounds Infected with Methicillin-Resistant Staphylococcus aureus

ABSTRACT Quorum sensing is a mechanism through which a bacterial population receives input from neighboring cells and elicits an appropriate response to enable survival within the host. Inhibiting quorum sensing by RNAIII-inhibiting peptide (RIP) has been demonstrated as a very effective mode of prevention and therapy for device-associated staphylococcal infections and was tested here for healing of wounds that are otherwise resistant to conventional antibiotics. Wounds, established through the panniculus carnosus of BALB/c mice, were inoculated with 5 × 107 CFU of methicillin-resistant Staphylococcus aureus. Mice were treated with Allevyn, RIP-soaked Allevyn (containing 20 μg RIP), daily intraperitoneal teicoplanin (7 mg/kg of body weight), Allevyn and teicoplanin, and RIP-soaked Allevyn and daily intraperitoneal teicoplanin. The main outcome measures were quantitative bacterial culture and histological examination with assessment of microvessel density and of vascular endothelial growth factor (VEGF) expression in tissue sections. Treatment with RIP-soaked Allevyn together with teicoplanin injection greatly reduced the bacterial load to 13 CFU/g (control untreated animals had 108 CFU/g bacteria). All other treatments were also significantly effective but only reduced the bacterial load to about 103 CFU/ml. Histological examination indicated that only treatment with RIP-soaked Allevyn with teicoplanin injection restored epithelial, granulation, and collagen scores, as well as microvessel density and VEGF expression, to the levels found with uninfected mice. In conclusion, we observed that RIP may be useful for the management of infected wounds and that it could represent an exciting and future alternative to the conventional antibiotics, at present considered the gold-standard treatments for methicillin-resistant S. aureus infections.

Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis

Summary Background  Psoriasis is a Th1 immune‐mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the ‘psoriatic march’. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)‐α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis.

The mesenchymal stem cell profile in psoriasis.

Background  The expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) and the level of total oxyradical scavenging capacity have been evaluated extensively in the cutaneous cells of patients with psoriasis. As yet, no indications are available about the undifferentiated cells, the mesenchymal stem cells (MSCs), isolated from skin.

Effectiveness of antimicrobial photodynamic therapy with a single treatment of RLP068/Cl in an experimental model of Staphylococcus aureus wound infection

Background  Chronic leg ulceration is a common health problem. It is well known that a clinically relevant bacterial load in chronic cutaneous wounds interferes significantly with the normal process of healing. Staphylococcus aureus is the most important representative of the staphylococcal group which causes clinically relevant infections within immunocompetent patients.

Expression of vascular endothelial growth factor, apoptosis inhibitors (survivin and p16) and CCL27 in alopecia areata before and after diphencyprone treatment: an immunohistochemical study

Background  Alopecia areata (AA) is a relatively common inflammatory form of nonscarring hair loss of unknown pathogenesis, but possibly of autoimmune origin. Topical immunotherapy, using a potent contact allergen such as diphencyprone (DPC), is currently considered the most effective mode of treatment. However, the way in which DPC operates on hair follicles in AA still remains to be elucidated. Vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around hair follicles, and several studies provide evidence that apoptosis is a central element in the regulation of hair follicle and vascular regression. The cutaneous lymphocyte‐associated antigen (CLA) and the skin‐associated chemokine CCL27 highlight an important role for epithelial cells in controlling homeostatic lymphocyte trafficking.

Correlation between lipoprotein(a) and lipid peroxidation in psoriasis: role of the enzyme paraoxonase-1

Background  Psoriasis is a chronic, inflammatory skin disease associated with abnormal plasma lipid metabolism and with a high frequency of cardiovascular events. Modifications of plasma lipids and an increase in the levels of biochemical markers of lipid peroxidation have been reported in subjects with psoriasis, suggesting a relationship between psoriasis, lipoproteins and oxidative damage.

Effect of Allium Cepa-Allantoin-Pentaglycan Gel on Skin Hypertrophic Scars: Clinical and Video-Capillaroscopic Results of an Open-Label, Controlled, Nonrandomized Clinical Trial

BACKGROUND Hypertrophic scar formation is a process in which prolonged angiogenesis sustained by vascular endothelial growth factor cutaneous expression plays an important role. OBJECTIVE This in vivo study was conducted to evaluate the clinical effect of a topical gel containing onion extract, allantoin, and pentaglycan on hypertrophic scars and keloids. MATERIALS AND METHODS Thirty people with hypertrophic scars or keloids were examined. Fifteen patients received a topical application of a gel containing allium cepa, allantoin, and pentaglycan twice a day for 24 weeks, the remaining 15 patients received no topical treatments. A clinical evaluation and an intravital videocapillaroscopy were performed on every patient at baseline (T0) and 24 weeks (T24) after the treatment. RESULTS Only the patients who received the topical treatment showed a significant reduction in neoangiogenetic features, demonstrated through an improvement of erythema and all videocapillaroscopic markers of neoangiogenesis. These changes induced by therapy led to a general improvement of the lesions. CONCLUSION Topical applications of a gel containing allium cepa, pentaglycan, and allantoin twice a day for 24 weeks seems to be useful in reducing neoangiogenesis in hypertrophic scars and keloids, resulting in clinical improvement of skin lesions. The authors have indicated no significant interest with commercial supporters.