GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses.

BACKGROUND AND PURPOSE: Strategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-ß (Aß) levels. EXPERIMENTAL APPROACH: To measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Aß peptides were measured in hippocampal tissues and cultured N2a cells by elisa. KEY RESULTS: GEBR-7b increased hippocampal cAMP, did not influence Aß levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents. CONCLUSION AND IMPLICATIONS: Our results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment.

Microbiological surveillance of hospital ventilation systems in departments at high risk of nosocomial infections.

The air in hospital wards with patients at high risk (Surgeries, Intensive Care Units and Bone Marrow Transplant Centers) has been surveyed less than the one in Operating Rooms. Therefore in this study we considered useful to verify the microbic contamination of the air of those wards evaluating the consistency of ventilation systems in relation also to the presence and location of HEPA absolute filters. Seven departments of Genoese San Martino Hospital at high risk of infection were taken into account. In there, environmental investigations have been performed by air samplings and by analyzing bacterial and fungal growth on plates after an incubation period. Almost 60% of all samples taken in wards yielded a positive result and the average values of bacterial and aspergillar charges measured at air flow emission openings decisively exceed the ones considered standard in operating rooms. Still, the average values of airborne bacterial charges were significantly higher in those wards equipped with central filters (p < 0.001), while as far as the aspergillar charge is concerned, no statistically relevant differences were noticed. In wards with ventilation system, the bacterial charge value raises from the emission grids to the middle of the room and to the aspiration grids, while the ward not equipped with a ventilation system presents in the middle of the room an average bacterial charge 2 to 10 times higher than the one in other wards. The average values regarding bacterial and aspergillar charges resulted quite high in all the departments surveyed. Nevertheless, if we take into account ventilation systems equipped with absolute filters HEPA located centrally or peripherally, it can be outlined that the air quality from the point of view of both microbic and aspergillar contamination turns out to be decisively better in systems with peripheral filters. Moreover, a compared analysis of the three Hematology wards allows us to infer that the presence of artificial ventilation systems can lower the bacterial and fungal compared with a ward with natural ventilation.