Synthesis and in Vitro Characterisation of Ifenprodil‐Based Fluorescein Conjugates as GluN1/GluN2B N‐Methyl‐D‐aspartate Receptor Antagonists

GluN2B‐containing NMDA receptors are involved in many important physiological functions and play a pivotal role in mediating pain as well as in several neurodegenerative disorders. We aimed to develop fluorescent probes to target the GluN2B subunit selectively in order to allow better understanding of the relationships between receptor localisation and physiological importance. Ifenprodil, known as the GluNR2B antagonist of reference, was chosen as the template for the elaboration of probes. We had previously reported a fluorescein conjugate that was shown (by confocal microscopy imaging of DS‐red‐labelled cortical neurons) to bind specifically to GluN2B. To elaborate this probe, we explored the influence of both the nature and the attachment point of the spacer between the fluorophore and the parent compound, ifenprodil. We performed chemical modifications of ifenprodil at the benzylic position and on the phenol ring by introducing secondary amine or amide functions and evaluated alkyl chains from two to 20 bonds either including or not including secondary amide functions as spacers. The previously developed probe was found to display the greatest activity in the inhibition of NMDA‐induced Ca²⁺ influx by calcium imaging experiments on HEK293 cells transfected with the cDNA encoding for GluN1‐1A and GluN2B. Further investigations revealed that this probe had a neuroprotective effect equivalent to that of ifenprodil in a standard test for neurotoxicity. Despite effects of lesser amplitude with these probes relative to ifenprodil, we demonstrated that they displaced [³H]ifenprodil in mouse brain slices in a similar manner.     

Phase Diagram for the 0.4Pb(Ni1/3,Nb1/3)O3–0.6Pb(Zr,Ti)O3 Solid Solution in the Vicinity of a Morphotropic Phase Boundary

A phase diagram based on dielectric-permittivity-versus-temperature measurements and high-temperature X-ray diffractometry was proposed for 0.4Pb(Ni_1/3,Nb_1/3)O₃- x PbZrO₃-(0.6- x )PbTiO₃ (0.2 lessthan equal to x lessthan equal to 0.32) relaxor-ferroelectric solid solution, and a morphotropic phase boundary that sharply bends toward zirconium-rich compositions was found. A spontaneous normal-to-relaxor ferroelectric transition was also observed when heating was performed for all the compositions tested near the morphotropic phase boundary. Additional considerations about previously published phase diagrams for Pb(Zn_1/3,Nb_2/3)O₃-PbTiO₃ and Pb(Mg_1/3,Nb_1/3)O₃-PbTiO₃ might lead to an extension of the presented diagram to these compositions.     

Different distribution of H1-H2 Epstein-Barr virus variant in oropharyngeal virus and in biopsies of Hodgkin''s disease and in nasopharyngeal carcinoma from Algeria

Ten clinical and food Listeria monocytogenes strains isolated during the epidemiological investigations of episodes of listeriosis (one outbreak and two sporadic cases) that occurred in northern Italy during 1993-1995 have been examined by DNA macrorestriction pattern analysis obtained by PFGE and RAPD typing, in order to confirm the food vehicle of infections. The same DNA profiles within the isolates from the three episodes were obtained by both techniques. The Apal and Smal PFGE profiles and RAPD patterns with primer OPM-01 confirmed the close relationship between strains from two distinct episodes. However, RAPD analysis with primer UBC-127 distinguished between these L. monocytogenes isolates.     

Epidemiologic surveillance in the Army and Public Health: as exemplified by rubella

Since 1993, several outbreaks of rubella are annually reported from the French military. This trend reveals a transfer of the reservoir of wild virus towards a non-immune population of male adolescents and young adults, as a result of the rubella control programmes. This paradoxical phenomenon should disappear within the next decade, when the new vaccinal schedule including a combined measles, mumps and rubella vaccine for the children of both sexes 11 to 13 years old will have been implemented. Meanwhile, the military system of weekly epidemiological report will be usable as a national observatory for the rubella. Moreover, providing specific data in real time, it will be able to support a strategy of intervention for an early neutralization of epidemics.