Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?

The process of epidermal renewal persists throughout the entire life of an organism. It begins when a keratinocyte progenitor leaves the stem cell compartment, undergoes a limited number of mitotic divisions, exits the cell cycle, and commits to terminal differentiation. At the end of this phase, the postmitotic keratinocytes detach from the basement membrane to build up the overlaying stratified epithelium. Although highly coordinated, this sequence of events is endowed with a remarkable versatility, which enables the quiescent keratinocyte to reintegrate into the cell cycle and become migratory when necessary, for example after wounding. It is this versatility that represents the Achilles heel of epithelial cells allowing for the development of severe pathologies. Over the past decade, compelling evidence has been provided that epithelial cancer cells achieve uncontrolled proliferation following hijacking of a "survival program" with PI3K/Akt and a "proliferation program" with growth factor receptor signaling at its core. Recent insights into adhesion receptor signaling now propose that integrins, but also cadherins, can centrally control these programs. It is suggested that the two types of adhesion receptors act as sensors to transmit extracellular stimuli in an outside-in mode, to inversely modulate epidermal growth factor receptor signaling and ensure cell survival. Hence, cell-matrix and cell-cell adhesion receptors likely play a more powerful and wide-ranging role than initially anticipated. This Perspective article discusses the relevance of this emerging field for epidermal growth and differentiation, which can be of importance for severe pathologies such as tumorigenesis and invasive metastasis, as well as psoriasis and Pemphigus vulgaris.

Ocular cicatricial pemphigoid antigen: Partial sequence and biochemical characterization

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of β4-integrin. The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as β4-integrin by its reaction with polyclonal and monoclonal antibodies to human β4-integrin. Sera from patients with bullous pemphigoid, pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding. These data strongly implicate a role for human β4-integrin in the pathogenesis of OCP. It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases. Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of cicatricial pemphigoid and help distinguishing them from bullous pemphigoid. This study highlights the function and importance of β4-integrin in maintaining the attachment of epithelial cells to the basement membrane.

Reacções adversas a fármacos com manifestações na mucosa oral

Existe uma grande quantidade de fármacos que provocam reacções adversas na mucosa oral. Os efeitos que causam são variados, nomeadamente angioedema, língua pilosa nigra, bruxismo, síndrome da boca ardente, candidose, queilite, xerostomia, eritema multiforme, hiperplasia gengival, glossite, halitose, hiperpigmentação das mucosas, hipersalivação, reações liquenóides, lupóides, penfigóides e tipo pênfigo, osteonecrose, tumefação das glandulas salivares, alterações do paladar, ulcerações, mucosite e lesões potencialmente malignas, entre outras. Com o presente trabalho pretende-se criar uma base de dados que facilite a pesquisa dos diferentes efeitos adversos e relação com a terapêutica prescrita ao paciente, de modo a auxiliar a vida ao Médico Dentista no contexto da prestação de serviços aos seus Utentes.

Survey of parasitic infection of Sander lucioperca (Linnaeus, 1758) and Silurus glanis (Linnaeus, 1758) in Aras reservoir with emphasizes of monogenean parasites

The parasites fauna of 491 specimens of Sander lucioperca, Linnaeus 1758 (246 specimens) and catfish, Silurus glanis, Linnaeus 1758 (245 specimens) in different size from Aras Reservoir situated in North —west of the Iran was investigated. During 2006-2007 Totally 16 parasite species were recorded. The most various parasites was found in catfish (10 species) while the lowest number was recorded in Sander lucioperca (6 species). Among them, however three genera of protozoa (Trichodina, Vorticella, Ichthyophthirius), two genera of Monogenea (Gyrodactylus, Silurodiscoides), Digenea, Cestoda, Nematoda, Acanthocephala and Annelida one species each (Diplostomum, Protocephalus, Eustrongylides, Neoechinorhynchus, Pisicola) and two crustacean genera (Argulus and Lernea) recorded and we can come to conclusion in comparison with the earlier data the actual parasite fauna of two hosts has been greatly improved. According to the present study the prevalence, mean abundance and mean intensity of parasites species of both hosts were highly influenced by seasons of the year. Some species found, however show a tendency to be more abundant ides Trichodina sp., Ichthyophthirius multifiliis, Silurodiscoides vistolensis, Protocephalus osculatus respectively. Most parasites species live in gills and skin, where is highly sensitive to some pathogens parasites species (Trichodina, Vorticella, Ichthyophthirius, Pisicola geometra, Argulus foliaceus; Lernea) and While some are specialist (Silurodiscoides vistolensis and Silurodiscoides siluri) other more or less generalist (ichthyophthirius).