Absence of association between pyronaridine in vitro responses and polymorphisms in genes involved in quinoline resistance in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess the <it>in vitro </it>cross-resistance of pyronaridine with other quinoline drugs, artesunate and several other commonly used anti-malarials and to evaluate whether decreased susceptibility to pyronaridine could be associated with genetic polymorphisms in genes involved in reduced quinoline susceptibility, such as <it>pfcrt</it>, <it>pfmdr1</it>, <it>pfmrp </it>and <it>pfnhe</it>.</p> <p>Methods</p> <p>The <it>in vitro </it>chemosusceptibility profiles of 23 strains of <it>Plasmodium falciparum </it>were analysed by the standard 42-hour ³H-hypoxanthine uptake inhibition method for pyronaridine, artesunate, chloroquine, monodesethylamodiaquine, quinine, mefloquine, lumefantrine, atovaquone, pyrimethamine and doxycycline. Genotypes were assessed for <it>pfcrt</it>, <it>pfmdr1</it>, <it>pfnhe-1 </it>and <it>pfmrp </it>genes.</p> <p>Results</p> <p>The IC₅₀values for pyronaridine ranged from 15 to 49 nM (geometric mean = 23.1 nM). A significant positive correlation was found between responses to pyronaridine and responses to artesunate (<it>r²</it>= 0.20; <it>P </it>= 0.0317) but too low to suggest cross-resistance. No significant correlation was found between pyronaridine IC₅₀and responses to other anti-malarials. Significant associations were not found between pyronaridine IC₅₀and polymorphisms in <it>pfcrt</it>, <it>pfmdr1</it>, <it>pfmrp </it>or <it>pfnhe-1</it>.</p> <p>Conclusion</p> <p>There was an absence of cross-resistance between pyronaridine and quinolines, and the IC₅₀values for pyronaridine were found to be unrelated to mutations in the transport protein genes <it>pfcrt</it>, <it>pfmdr1</it>, <it>pfmrp </it>or <it>pfnhe-1</it>, known to be involved in quinoline resistance. These results confirm the interest and the efficacy of the use of a combination of pyronaridine and artesunate in areas in which parasites are resistant to quinolines.</p

Calibration of a superconducting gravimeter: a comparison between the mass attraction method and the use of FG5 absolute gravity mesurements

The Superconducting Gravimeter GWR T015 is recording continuously in a laboratory of ENEA (Italian National Institute for Energy Development) at Brasimone site, in the Apennines between Bologna and Florence (Italy). The gravimeter is routinely calibrated by means of a moving mass system with a precision of about 0.3%. In October 1997 a comparison campaign between the absolute gravimeter FG5-206 of EOST (Ecole et Observatorie des Sciences de la Terre) of Strasbourg and the Superconducting Gravimeter (SC) itself has been performed, in order to verify and to improve the precision of the calibration factor of the Sc gravimeter. The seismic noise due to the Umbria-Marche swarm earthquakes didn't effect the measurements, and the result of the comparison campaign agrees with the mass system at a level of 0.06%. The calibration constant of the SC gravimeter has been improved by a factor 2.5.Published583-5881.8. Osservazioni di geofisica ambientaleN/A or not JCRreserve

Local hydrology, the Global Geodynamics Project and CHAMP/GRACE perspective: some case studies

International audienceWe first quantify the influence of aquifers on gravity variations by considering local, regional and continental scales. We show that locally only the direct attraction of the underlying aquifer has to be taken into account. At continental (or global scales), the underground water masses act by direct attraction (due to the earth curvature), loading flexure and potential redistribution. We show that at the intermediate regional scale (saying a few kilometres to a few hundreds of kilometres), groundwater contributions can be neglected in practice. Afterwards, we illustrate the difficulties in tackling the local hydrological context by studying comparatively the geological and hydrogeological surroundings of three European Global Geodynamics Project (GGP) superconducting gravimeter stations (Strasbourg, Moxa, and Vienna). Finally, it appears clearly that hydrological variability and cycle characterisations constitute the up-to-date challenge while studying gravity variations in a large spectral range. That is why, gravity is used to quantify hydrological transfers, and overall when seeking for small signals from the Earth's deep interior or other environmental signals (atmosphere, oceans) where groundwater influence can be seen as a disturbance

The Gravimetric Station of Brasimone: results of an intercomparison experiment between gravimeters

The GWR Superconducting Gravimeter (T015) is working continuously in a laboratory of the Research Center of ENEA (Italian National Institute for Energy Development)since 1995 in the frame of Global Geodynamics Project. The data are periodically send to the ICET to be analysed and to produce a valuable tool of high precision monitoring of the global gravity field. The superconducting gravimeter is periodically calibrated by means of a moving mass system with a precision better than 0.3%. In October 1997 a campaign involving the FG5-206 of the Institut de Physique du Globe of Strasbourg was performed in order to verify and to improve the calibration constant of the superconducting gravimeter (SC). The SC calibration constant was computed with the help of absolute gravity and with the mass system. In spite of the large amount of seismic noise present in the data, a good agreement between the two methods, at the 0.1% level, was obtained, improving the calibration factor of the SC gravimeter by a factor of three.Published137-1441.8. Osservazioni di geofisica ambientaleN/A or not JCRreserve

Methods for computing the internal flattening, with applications to the Earth's structure and geodynamics

International audienc

The Gravimetric Station of Brasimone: results of an intercomparison experiment between gravimeters

The GWR Superconducting Gravimeter (T015) is working continuously in a laboratory of the Research Center of ENEA (Italian National Institute for Energy Development)since 1995 in the frame of Global Geodynamics Project. The data are periodically send to the ICET to be analysed and to produce a valuable tool of high precision monitoring of the global gravity field. The superconducting gravimeter is periodically calibrated by means of a moving mass system with a precision better than 0.3%. In October 1997 a campaign involving the FG5-206 of the Institut de Physique du Globe of Strasbourg was performed in order to verify and to improve the calibration constant of the superconducting gravimeter (SC). The SC calibration constant was computed with the help of absolute gravity and with the mass system. In spite of the large amount of seismic noise present in the data, a good agreement between the two methods, at the 0.1% level, was obtained, improving the calibration factor of the SC gravimeter by a factor of three