Incorporating 'reason for use' into the prescribing process of medication: a survey on the opinion of patients in Flanders, Belgium.

BACKGROUND: A longstanding debate exists about including a 'reason for use' on prescriptions for medication. Little is known, however, about patients' opinions on this subject. METHODS: An internet-based questionnaire, consisting mainly of Likert scale questions, was distributed online to the general public in Belgium. Results from 1034 responses were analyzed using descriptive statistics. RESULTS: Opinions from patients toward including a 'reason for use' on medication prescriptions were generally positive. A clear majority of 62% increased to 74% after providing information about the possible link between indication and medication dose. A majority of the participants expressed a positive attitude regardless of the pathology involved, although sexually transmitted diseases were of greatest concern. Other important aspects differentiating the opinion positively was the transmission of this information in an electronic-only form and limiting it to the regular pharmacist excluding further use by third parties such as other pharmacies or insurance companies. Patients using multiple medicines and those frequenting the same pharmacy also had a more favorable opinion about including the reason for use. In addition, analysis of physician and pharmacist questionnaire responses, explicitly excluded from the main analysis, confirmed the known contrasting opinions in these subgroups. CONCLUSIONS: Patients have strong support for transferring information on the 'reason for use' of their prescriptions to their regular pharmacy if this is done in a secure and privacy-conscious way enabling increased patient safety and improved pharmaceutical care.

Effect of non-steroidal anti-inflammatory drugs on amyloid-beta formation and macrophage activation after platelet phagocytosis.

Recently, we showed that platelet phagocytosis occurs in human atherosclerotic plaques and leads to foam cell formation. Platelet phagocytosis, resulting in macrophage activation and iNOS induction, was associated with the formation of amyloid-beta peptide (Abeta) via proteolytic cleavage of platelet-derived amyloid precursor protein (APP), possibly by secretases. To test the involvement of gamma-secretase in this process, we used indomethacin, ibuprofen, and sulindac sulfide, non-steroidal anti-inflammatory drugs (NSAIDs) known to alter the gamma-secretase cleaving site of APP, on their ability to inhibit macrophage activation evoked by platelet phagocytosis. J774 macrophages were incubated with human platelets or lipopolysaccharide (LPS) with or without NSAIDs. Nitrite was quantified as a measure for inducible nitric oxide synthase (iNOS) activity. Indomethacin, ibuprofen, sulindac sulfide, and meloxicam concentration-dependently reduced nitrite production by macrophages incubated with platelets, but did not alter LPS-induced iNOS activity or platelet uptake. However, acetylsalicylic acid and naproxen, two NSAIDs without effect on the gamma-secretase cleaving site of APP, did not affect nitrite production in either platelet- or LPS-stimulated macrophages. Surface-enhanced laser desorption/ionization time-of-flight mass-spectrometry demonstrated time-dependent formation of Abeta-containing peptides after platelet phagocytosis, which could be inhibited by indomethacin. In conclusion, these results point to the involvement of gamma-secretase in macrophage activation following platelet phagocytosis.

Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis.

In human occluded saphenous vein grafts, we previously demonstrated cytotoxic foam cells, presumably derived from macrophages engulfing platelets. In the present study, we investigated whether platelet phagocytosis occurs in human atherosclerotic plaques, whether this activates macrophages, and whether the platelet constituent, amyloid precursor protein (APP), was involved. Immunohistochemistry documented the presence of APP, beta-amyloid peptide (Abeta, cleaved from APP), and platelets (CD9), along with inducible NO synthase (iNOS) and cyclooxygenase-2, two markers of macrophage activation, around microvessels in advanced human carotid artery plaques (n=18). Abeta colocalized with iNOS-expressing macrophages that were often surrounded by platelets. In vitro, murine J774 and human THP-1 macrophages were incubated with or without washed human platelets. Coincubation of macrophages and platelets led to platelet phagocytosis (electron and confocal microscopy) and formation of lipid-, APP-, and Abeta-containing foam cells. These expressed iNOS mRNA (reverse transcription-polymerase chain reaction) and protein and produced nitrite and tumor necrosis factor-alpha (ELISA). Macrophage pretreatment with 4-(2-aminoethyl)benzenesulfonyl fluoride, a protease inhibitor, reduced APP processing and inhibited NO biosynthesis induced by platelet phagocytosis but not by lipopolysaccharides. Human atherosclerotic plaques and J774 and THP-1 macrophages contained mRNA of the APP-cleaving enzyme beta-secretase. This is the first demonstration of Abeta, a peptide extensively studied in Alzheimer's disease, in human atherosclerotic plaques. It was present in activated iNOS-expressing perivascular macrophages that had phagocytized platelets. In vitro studies indicate that platelet phagocytosis leads to macrophage activation and suggest that platelet-derived APP is proteolytically processed to Abeta, resulting in iNOS induction. This represents a novel mechanism for macrophage activation in atherosclerosis.