Retinal pigment epithelium-immune system interactions: Cytokine production and cytokine-induced changes

Vision is dependent on proper function of several intraocular structures. Immune responses to eliminate invading pathogens from the eye may threat vision by causing damage to these structures. Therefore, immunological defence of the eye should be carefully balanced between efficacy and maintenance of functional integrity. The eye is equipped with several regulatory mechanisms to prevent certain immune and inflammatory responses and is, therefore, regarded as an immune privileged site. The retinal pigment epithelium (RPE) contributes to the immune privileged status of the eye as part of the blood-eye barrier and by the secretion of immunosuppressive factors inside the eye. RPE cells, however, may also play an important role in the development of immune and inflammatory responses in the posterior part of the eye. During the last decade it has become clear that RPE cells are highly sensitive to a variety of inflammatory cytokines. Under inflammatory conditions, RPE cells produce a myriad of cytokines that may activate the resident ocular cells or attract and activate leukocytes. Cytokine stimulation of RPE cells causes profound effects, including nitric oxide secretion, cell surface expression of MHC class II and adhesion molecules and abrogation of barrier function. This article provides a comprehensive review of the literature concerning RPE cells and cytokines. (C) 2000 Elsevier Science Ltd

Quality of drug label information on QT interval prolongation

Background: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. Objective: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product characteristics (SPC) of recently approved medicinal products. Methods: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. Results: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT-prolongation': 100%). Conclusions: The extent and content of information on QT-prolongation varies considerably between SPCs, and in almost half of the drugs a clear message on QT-prolongation was lacking in the SPC