Walid Medhat

A role for caveolin-1 in desmoglein binding and desmosome dynamics

Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expressed in human skin carcinomas. In addition to its well-known role in mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote cancer development and progression. However, the mechanisms by which Dsg2 activates these signaling pathways and the relative contribution of its signaling and adhesion functions in tumor progression are poorly understood. In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major protein of specialized membrane microdomains called caveolae, which functions in both membrane protein turnover and intracellular signaling. Sequence analysis revealed that Dsg2 contains a putative Cav-1-binding motif. A permeable competing peptide resembling the Cav-1 scaffolding domain bound to Dsg2, disrupted normal Dsg2 staining and interfered with the integrity of epithelial sheets in vitro. Additionally, we observed that Dsg2 is proteolytically processed; resulting in a 95-kDa ectodomain shed product and a 65-kDa membrane-spanning fragment, the latter of which localizes to lipid rafts along with full-length Dsg2. Disruption of lipid rafts shifted Dsg2 to the non-raft fractions, leading to the accumulation of these proteins. Interestingly, Dsg2 proteolytic products are elevated in vivo in skin tumors from transgenic mice overexpressing Dsg2. Collectively, these data are consistent with the possibility that accumulation of truncated Dsg2 protein interferes with desmosome assembly and/or maintenance to disrupt cell–cell adhesion. Furthermore, the association of Dsg2 with Cav-1 may provide a mechanism for regulating mitogenic signaling and modulating the cell-surface presentation of an important adhesion molecule, both of which could contribute to malignant transformation and tumor progression.

Efficacy of mesotherapy in facial rejuvenation: a histological and immunohistochemical evaluation

Background  Mesotherapy, commonly known as “biorejuvenation” or “biorevitalization”, is a technique used to rejuvenate the skin by means of a transdermal injection of a multivitamin solution and natural plant extracts that are thought to improve the signs of skin aging.

Fractional versus ablative erbium:yttrium-aluminum-garnet laser resurfacing for facial rejuvenation: An objective evaluation

BACKGROUND Laser is one of the main tools for skin resurfacing. Erbium:yttrium-aluminum-garnet (Er:YAG) was the second ablative laser, after carbon dioxide, emitting wavelength of 2940 nm. Fractional laser resurfacing has been developed to overcome the drawbacks of ablative lasers. OBJECTIVE We aimed to objectively evaluate the histopathological and immunohistochemical effects of Er:YAG 2940-nm laser for facial rejuvenation (multiple sessions of fractional vs single session of ablative Er:YAG laser). METHODS Facial resurfacing with single-session ablative Er:YAG laser was performed on 6 volunteers. Another 6 were resurfaced using fractional Er:YAG laser (4 sessions). Histopathological (hematoxylin-eosin, orcein, Masson trichrome, and picrosirius red stains) and immunohistochemical assessment for skin biopsy specimens were done before laser resurfacing and after 1 and 6 months. Histometry for epidermal thickness and quantitative assessment for neocollagen formation; collagen I, III, and VII; elastin; and tropoelastin were done for all skin biopsy specimens. RESULTS Both lasers resulted in increased epidermal thickness. Dermal collagen showed increased neocollagen formation with increased concentration of collagen types I, III, and VII. Dermal elastic tissue studies revealed decreased elastin whereas tropoelastin concentration increased after laser resurfacing. Neither laser showed significant difference between their effects clinically and on dermal collagen. Changes in epidermal thickness, elastin, and tropoelastin were significantly more marked after ablative laser. LIMITATIONS The small number of patients is a limitation, yet the results show significant improvement. CONCLUSION Multiple sessions of fractional laser have comparable effects to a single session of ablative Er:YAG laser on dermal collagen but ablative laser has more effect on elastic tissue and epidermis.

Effects of the Nd:YAG 1320-nm laser on skin rejuvenation: Clinical and histological correlations

Abstract The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is a popular non-ablative treatment used for skin rejuvenation. The purpose of this prospective study was to evaluate the clinical effects, coupled with a quantitative assessment, of the histological changes in response to Nd:YAG 1320-nm laser treatment of periocular wrinkles. Six volunteers with Fitzpatrick skin types III and IV and Glogau class I–II wrinkles were subjected to 3 months of Nd:YAG 1320-nm treatment in the periocular area (six sessions at 2-week intervals). Volunteers were photographed, and skin biopsies were obtained at baseline as well as 3 and 6 months after the start of treatments. Quantitative evaluation of total elastin, newly synthesized tropoelastin, collagen types I, III and VII, and newly synthesized collagen was performed using a computerized morphometric analysis. A noticeable clinical and histological improvement was observed after Nd:YAG 1320-nm treatment. Collagen types I, III and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased after treatment. Our data suggest that Nd:YAG 1320 nm is an effective treatment for skin rejuvenation as it stimulates the repair processes, and reverses the clinical, as well as the histopathological, signs of skin aging.

Multiple fractional erbium: yttrium–aluminum–garnet laser sessions for upper facial rejuvenation: clinical and histological implications and expectations

Fractional photothermolysis is a modern resurfacing technique, in which microscopic zones of thermal injury are created, stimulating turnover of both epidermis and dermis. Fractional laser rejuvenation has been developed to overcome the drawbacks of traditional ablative laser.

Minimally invasive facial rejuvenation: current concepts and future expectations

Aging of the skin is a multifactorial phenomenon in which ongoing intrinsic changes combine the cumulative effects of chronic exposure to the elements, primarily UV radiation, in a synergistic fashion, causing the skin to lose its thickness and elasticity and develop wrinkles. There is now an increased interest in a wide range of non-ablative treatments for skin aging, which are used to rejuvenate skin with minimal downtime and complications. As the demand for minimally invasive rejuvenation is increasing, different modalities have been designed to produce favorable alterations in the dermis with no epidermal damage via photomodulation, selective photothermolysis, fractional photothermolysis, radio waves, electro-optical synergy, injectable fillers, neurotoxins, skin needling and biorejuvenation to stimulate collagen synthesis and rejuvenate the aged skin while preserving the integrity of the epidermis.

Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated by Pemphigus Foliaceus Antibodies and Exfoliative Toxins

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-α, Dsg1-β, and, to a lesser extent, Dsg1-γ, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

Multiple microneedling sessions for minimally invasive facial rejuvenation: an objective assessment

Microneedling or percutaneous collagen induction is a new modality used for skin rejuvenation, tightening, and scar remodeling. It offers a simple and effective treatment for photoaged skin with minimal disruption of the epidermis, thus limiting adverse effects and minimizing downtime.

Forehead wrinkles: a histological and immunohistochemical evaluation

Wrinkles are associated with cutaneous aging especially on sun‐exposed skin. Despite they are considered a major topic in cosmetic dermatology, very few reports have studied the specific histological and immunohistochemical changes characteristic for wrinkles.

Multiple minimally invasive Erbium: Yttrium Aluminum Garnet laser mini‐peels for skin rejuvenation: an objective assessment

Background  As the demand for minimally invasive rejuvenation is increasing, micropeel resurfacing using Erbium:Yttrium Aluminum Garnet (Er:YAG) laser 2940 nm has been reported for the treatment of photoaged skin without ablation of the epidermis. However, little is known about the efficacy and underlying histologic changes associated with this type of treatment.