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P Grellier

Publications and source records attributed to P Grellier.

107 records · Page 6Linked to original sources
PubMedDate not supplied

Host cell and malarial targets for docetaxel (Taxotere) during the erythrocytic development of Plasmodium falciparum.

The microtubular stabilizing agent docetaxel (Taxotere) is known to inhibit the intraerythrocytic development of Plasmodium falciparum. To investigate the mechanism(s) of inhibition, we analyzed the structural organization of the mitotic spindle by immunofluorescence and electron microscopy. When 30 microM docetaxel was applied for five hours on ring forms, alterations in the mitotic spindles leading to abnormal nuclear divisions were observed. At the trophozoite- and schizont-stage, docetaxel pulses prevent mitosis by stabilizing microtubular structures associated with the mitotic apparatus, giving abnormal spindles. However, this inhibition did not interfere with parasite DNA synthesis indicating the absence of a checkpoint that couples exit from mitosis with proper spindle assembly as observed in higher eukaryotic cells. In parallel, intraerythrocytic concentration of docetaxel was measured in parasitized erythrocytes, after incubation of cells with 3H-docetaxel for five hours. It was found to be 14-fold increased at the ring-stage of infected erythrocytes compared to normal ones, 170-fold increased at the trophozoite-stage and 1,500-fold increased at the schizont-stage. Our data show that, even though the overall intracellular concentration of docetaxel is low in docetaxel-pulsed rings, the agent might be sufficient to disturb the spindle organization. However, the existence of targets for docetaxel other than mitotic spindle microtubules, i.e. erythrocyte membrane components could interfere with mitotic spindle formation.

Animals↗
PubMedDate not supplied

[Non discal surgical sciatic neuralgia (author's transl)].

Non discal sciatic neuralgia accounts for 5 per cent of all cases of surgical sciatica. They are divided into four groups: central sciatica very seldom, cordal and root sciatica more common and truncal sciatica. These sciatica are dominated by atypical clinical features: atypical provoking factor, atypical character, atypical topography and therapy. A good x-rays study is necessary involving myelography, angiography of the spine etc., but discography and lumbar phlebography are not useful. A rapid review of aetiologies shows that they cover a wide area and that therapy must be debated for each case.

Diagnosis, Differential↗