Hypersensitivity Reactions to Ophthalmic Products
Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Policlinico, Piazza G. Cesare no 11, 70124 Bari, Italy.Current pharmaceutical design (Impact Factor: 3.45). 02/2006; 12(26):3401-10. DOI: 10.2174/138161206778194024
Adverse reactions after administration of ophthalmic products have frequently been observed. These reactions can be provoked by both active principles and excipients. Different pathogenic mechanisms have been suggested for such reactions, including immunologic ones. Basophils and mast cells participate in IgE-mediated reactions through the release of mediators like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most delayed reactions, particularly conjunctival ones and eyelid dermatitis. Prick tests and immediate-reading intradermal tests are carried out to diagnose immediate hypersensitivity reactions, while patch tests are usually performed to evaluate delayed reactions. Other diagnostic tests, such as serum-specific IgE assays in immediate reactions, as well as delayed-reading intradermal tests and/or lymphocyte transformation tests in delayed ones, are rarely performed. In this review, particular attention is addressed to the clinical and practical aspects of both cell-mediated and IgE-mediated hypersensitivity reactions to ophthalmic products.
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ABSTRACT: Tryptases comprise a group of trypsin-like serine proteases that are highly and selectively expressed in mast cells and to a lesser extent in basophils. Among them interest has been focused on tryptase β, primarily because it was the first tryptase identified and because it is the predominant protease and protein component of mast cells. Subsequent studies have provided convincing evidence that tryptase β is not only a clinically useful marker of mast cells and their activation but that it contributes to the pathogenesis of allergic inflammatory disorders, most notably asthma. The pathogenetic relevance together with the apparent lack of overt physiological functions has caused considerable interest in β-tryptase as a potential therapeutic target. Meanwhile diverse tryptase inhibitors have been synthesized whose design in part was fostered by the structural analysis of the enzymatically active β tryptase tetramer. Various compounds have been studied both in animal models and in man, providing proof of principle that tryptase inhibitors have therapeutic potential in asthma. Here we review the rationale to develop tryptase inhibitors and the approaches pursued, and also try to pinpoint some of the problems that hamper the development of clinically applicable drugs.
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