50 research outputs found

    Aquaporins: important but elusive drug targets.

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    The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

    Cell motility: the integrating role of the plasma membrane

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    The plasma membrane is of central importance in the motility process. It defines the boundary separating the intracellular and extracellular environments, and mediates the interactions between a motile cell and its environment. Furthermore, the membrane serves as a dynamic platform for localization of various components which actively participate in all aspects of the motility process, including force generation, adhesion, signaling, and regulation. Membrane transport between internal membranes and the plasma membrane, and in particular polarized membrane transport, facilitates continuous reorganization of the plasma membrane and is thought to be involved in maintaining polarity and recycling of essential components in some motile cell types. Beyond its biochemical composition, the mechanical characteristics of the plasma membrane and, in particular, membrane tension are of central importance in cell motility; membrane tension affects the rates of all the processes which involve membrane deformation including edge extension, endocytosis, and exocytosis. Most importantly, the mechanical characteristics of the membrane and its biochemical composition are tightly intertwined; membrane tension and local curvature are largely determined by the biochemical composition of the membrane and the biochemical reactions taking place; at the same time, curvature and tension affect the localization of components and reaction rates. This review focuses on this dynamic interplay and the feedbacks between the biochemical and biophysical characteristics of the membrane and their effects on cell movement. New insight on these will be crucial for understanding the motility process

    Soft tissue-related complications and management around dental implants.

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    Implant installation for replacing missing teeth is a frequent treatment procedure with high long-term survival and success rates. However, the success of implant therapy may be jeopardized by several complications related to mistakes in treatment planning, surgical procedure, management of hard and soft tissues, and infections. Increasing evidence suggests that the stability of the soft tissues surrounding osseointegrated dental implants may substantially influence long-term clinical stability and esthetics. Therefore, when implant therapy is planned, the clinician must not only be able to perform the appropriate steps to maintain/create a stable soft tissue, but also needs to be aware of the potential sources for complications and possess the adequate knowledge for their appropriate management. The present paper provides an overview of the most important aspects related to the prevention and management of soft tissue-related complications in conjunction with implant therapy. The current literature indicates that the presence of an adequate width of keratinized attached mucosa around dental implants may lead to better soft and hard tissue stability, less plaque accumulation, limited soft tissue recession, and lower incidence of peri-implant mucositis. Proper implant positioning by carefully considering appropriate mesio-distal and bucco-lingual dimensions and implant angulation may prevent the loss of interdental soft tissues and development of soft tissue recessions. To optimize the width of keratinized attached mucosa, the appropriate soft tissue augmentation protocol should be selected for each particular indication. When the use of autogenous soft tissue grafts is planned, a thorough knowledge of the anatomical structures is mandatory in order to harvest soft tissue grafts of an appropriate quality and quantity and to avoid/minimize postoperative complications. Finally, the clinician needs to master the necessary steps in order to manage complications related to extensive bleeding and tissue necrosis that may occur in conjunction with soft tissue augmentation procedures
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