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Various Disease States (various + disease_states)
Selected Abstracts2431: The eyelid margin: an underestimated contributor to ocular surface health and diseaseACTA OPHTHALMOLOGICA, Issue 2010E KNOP Purpose The eyelid margin is frequently underestimated in the consideration of factors in ocular surface health and disease. Clinically the whole free end of the lid margin is often addressed simply as "margin" without further differentiation. It is attempted to review the structure, embryology and function of the lid margin as well as its involvement in ocular surface pathology. Methods A review based on the available literature on the lid margin is prepared together with own findings on the histology of normal and pathological tissues. Results The human lid margin is divided into distinct zones that consist, coming from the skin side, of a rounded outer lid border, a free lid margin (between the eye lashes and the opening of the meibomian glands), the muco-cutaneous junction and a sharp inner lid border. The embryological development of the eye lids and their tissue components (loose connective tissue, lid muscles, ciliary hairs, Meibomian glands and vascular and neural components) takes place during the period of sealed lids. During this time the development of the Meibomian glands shows considerable similarity to that of the ciliary hairs. The sealing of the mesodermal lid folds and their eventual separation is dependent on several factors that may be involved in pathology. Various disease states, as well as the aging process, can lead to destruction of the lid margin and, conversely, this can lead to deterioration of the cornea and conjunctiva. Conclusion The eyelid margin is an underestimated contributor to ocular surface health and disease. Increased awareness of the anatomy, embryology, physiology and pathophysiology of the lid margin and it tissue components appears important for the preservation of ocular surface integrity. Support DFG KN317/11 [source] Role of protease-activated receptor-2 during cutaneous inflam-mation and the immune responseEXPERIMENTAL DERMATOLOGY, Issue 9 2004M. Steinhoff Protease-activated receptors (PARs) constitute a new subfamily of G-protein-coupled receptors with seven transmembrane domains which are activated by various serine proteases such as thrombin, cathepsin G, trypsin or tryptase, and bacterial proteases or mite antigens, for example. PAR2 is a receptor for mast cell tryptase or house dust mite allergens, which is released during inflammation and allergic reactions. In the skin, PAR2 is diversely expressed by keratinocytes, endothelial cells, and occasionally sensory nerves of human skin in various disease states. Moreover, immunocompetent cells such as T cells and neutrophils express functional PAR2, thereby contributing to inflammation and host defense. Own data revealed that PAR2 contributes to neurogenic inflammation by releasing neuropeptides from sensory nerves resulting in oedema, plasma extravasation and infiltration of neutrophils. Thus, mast cells may communicate with sensory nerves in inflammatory tissues by activating PAR2 via tryptase. Moreover, PAR2 agonists upregulate the expression of certain cell-adhesion molecules and cytokines such as interleukin-6 and interleukin-8 on dermal microvascular endothelial cells or regulate neutrophil migration, indicating that PAR2 plays an important role in leucocyte/endothelial interactions. These effects may be partly mediated by NF-,B, an important transcription factor during inflammation and immune response. PAR2 stimulation results in the activation of NF-,B on microvascular endothelial cells and keratinocytes, thereby regulating ICAM-1 expression. We also demonstrate evidence for a diverse expression of PAR2 in various skin diseases and highlight the recent knowledge about the important role of PAR2 during inflammation and the immune response. Together, PAR2 -modulating agents may be new tools for the treatment of inflammatory and allergic diseases in the skin. [source] Genetic and epigenetic mechanisms in the early development of the vascular systemJOURNAL OF ANATOMY, Issue 2 2006Domenico Ribatti Abstract The cardiovascular system plays a critical role in vertebrate development and homeostasis. Vascular development is a highly organized sequence of events that requires the correct spatial and temporal expression of specific sets of genes leading to the development of a primary vascular network. There have been intensive efforts to determine the molecular mechanisms regulating vascular growth and development, and much of the rationale for this has stemmed from the increasing clinical importance and therapeutic potential of modulating vascular formation during various disease states. [source] Use of proteomics for the identification of novel drug targets in brain diseasesJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Jose A. Morón Abstract In spite of the rapid advances in the development of the new proteomic technologies, there are, to date, relatively fewer studies aiming to explore the neuronal proteome. One of the reasons is the complexity of the brain, which presents high cellular heterogeneity and a unique subcellular compartmentalization. Therefore, tissue fractionation of the brain to enrich proteins of interest will reduce the complexity of the proteomics approach leading to the production of manageable and meaningful results. In this review, general considerations and strategies of proteomics, the advantages and challenges to exploring the neuronal proteome are described and summarized. In addition, this article presents an overview of recent advances of proteomic technologies and shows that proteomics can serve as a valuable tool to globally explore the changes in brain proteome during various disease states. Understanding the molecular basis of brain function will be extremely useful in identifying novel targets for the treatment of brain diseases. [source] Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damageJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Caroline R. Elliott-Hunt Abstract Expression of the neuropeptide galanin is up-regulated in many brain regions following nerve injury and in the basal forebrain of patients with Alzheimer's disease. We have previously demonstrated that galanin modulates hippocampal neuronal survival, although it was unclear which receptor subtype(s) mediates this effect. Here we report that the protective role played by galanin in hippocampal cultures is abolished in animals carrying a loss-of-function mutation in the second galanin receptor subtype (GalR2-MUT). Exogenous galanin stimulates the phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated kinase (ERK) in wild-type (WT) cultures by 435 ± 5% and 278 ± 2%, respectively. The glutamate-induced activation of Akt was abolished in cultures from galanin knockout animals, and was markedly attenuated in GalR2-MUT animals, compared with WT controls. In contrast, similar levels of glutamate-induced ERK activation were observed in both loss-of-function mutants, but were further increased in galanin over-expressing animals. Using specific inhibitors of either ERK or Akt confirms that a GalR2-dependent modulation in the activation of the Akt and ERK signalling pathways contributes to the protective effects of galanin. These findings imply that the rise in endogenous galanin observed either after brain injury or in various disease states is an adaptive response that reduces apoptosis by the activation of GalR2, and hence Akt and ERK. [source] Proteases implicated in apoptosis: old and newJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2010Kelly L. Moffitt Abstract Objectives The role of proteases in the regulation of apoptosis is becoming increasingly apparent. Whilst many of these proteases are already characterised, some have yet to be identified. Traditionally caspases held the traditional role as the prime mediators of apoptosis; however, attention is now turning towards the contribution made by serine proteases. Key findings As unregulated apoptosis is implicated in various disease states, the emergence of this proteolytic family as apoptotic regulators offers novel and alterative opportunities for therapeutic targets. Summary This review presents a brief introduction and overview of proteases in general with particular attention given to those involved in apoptotic processing. [source] Advances in proteomics data analysis and display using an accurate mass and time tag approachMASS SPECTROMETRY REVIEWS, Issue 3 2006Jennifer S.D. Zimmer Abstract Proteomics has recently demonstrated utility for increasing the understanding of cellular processes on the molecular level as a component of systems biology approaches and for identifying potential biomarkers of various disease states. The large amount of data generated by utilizing high efficiency (e.g., chromatographic) separations coupled with high mass accuracy mass spectrometry for high-throughput proteomics analyses presents challenges related to data processing, analysis, and display. This review focuses on recent advances in nanoLC-FTICR-MS-based proteomics approaches and the accompanying data processing tools that have been developed to display and interpret the large volumes of data being produced. © 2006 Wiley Periodicals, Inc., Mass Spec Rev 25:450,482, 2006 [source] Impact of oxidative stress on lung diseasesRESPIROLOGY, Issue 1 2009Hee Sun PARK ABSTRACT Reactive oxygen species (ROS) are products of normal cellular metabolism and are known to act as second messengers. Under physiological conditions, ROS participate in maintenance of cellular ,redox homeostasis' in order to protect cells against oxidative stress through various redox-regulatory mechanisms. Overproduction of ROS, most frequently due to excessive stimulation of either reduced nicotinamide adenine dinucleotide phosphate by cytokines or the mitochondrial electron transport chain and xanthine oxidase, results in oxidative stress. Oxidative stress is a deleterious process that leads to lung damage and consequently to various disease states. Knowledge of the mechanisms of ROS regulation could lead to the pharmacological manipulation of antioxidants in lung inflammation and injury. [source] | |||||||||||||