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Dans le cadre des travaux du groupe Essais laboratoire de présélectiondépendant du Groupement Français de Coordination (GFC), deux tests d'évaluation, de la tendance d'un lubrifiant pour moteur à former des dépôts à haute température, sont présentés : - Un nouveau test, le microcokage (fig. 1) qui est un essai statique de cokéfaction soumettant l'huile déposée sur une plaque en alliage d'aluminium à des gradients de température élevés et proches des conditions thermiques rencontrées dans la zone de segmentation d'un piston moteur. En fin d'essai, on détermine la température limite de stabilité de l'huile, exprimée par la température d'apparition de dépôts (fig. 2) et l'on évalue l'aspect et la quantité de dépôts existants sous forme de vernis, en attribuant une note, au mérite, à l'aide du système de cotation décrit dans la méthode d'évaluation de la propreté d'un moteur CEC M-02-A-78 (tableau 5 et fig. 5 et 10). L'association des deux méthodes d'appréciation permet de bien discriminer des huiles de différents niveaux. Des résultats d'essais inter-laboratoires concernant des huiles de référence européennes, pour 2 moteurs à essence et Diesel, sont présentés (tableau 7 et figs. 3 et 4). - Une amélioration d'un test de cokéfaction sur plaque inclinée (figs. 6 et 7) dans lequel un volume donné d'huile s'écoule en film mince sur une plaque en acier inoxydable portée à très haute température. Les dépôts formés en fin d'essai sont évalués, selon leur nature (carbone ou vernis) et leur importance, également suivant les principes de la méthode de cotation CEC (fig. 8 et 9). Par ailleurs, un système de cotation vidéo des plaques de microcokage par reconnaissance de couleur est présenté (fig. 11 et 12). Ce système, appelé Vidéo-Cotateur ,, permet de reproduire fidèlement la cotation visuelle (fig. 13), tout en éliminant les facteurs subjectifs de cette cotation. Les résultats obtenus avec ce système constituent une première étape sur la voie de la cotation de pièces de moteurs assistée par ordinateur (fig. 14). Within the framework of the research done by the Essais laboratoire de présélectiongroup, which depends on the Groupement Français de Coordination (GFC), two evaluation tests are described of the tendency of an engine lubricant to form deposits at high temperature :- A new microcoking test (Fig. 1), which is a static coking test subjecting an oil deposited on an aluminium alloy plate to high temperature gradients that are close to the thermal conditions encountered in the piston-ring zone of an engine. At the end of the test, the maximum stability temperature of the oil is determined, as expressed by the temperature at which deposits appear (Fig. 2), and the aspect and quantity of deposits existing in the form of varnish are evaluated by determining a rating by means of the rating system described in the CEC M-02-A-78 method for evaluating the cleanness of a engine (Table 5 and Figs. 5 and 10). The association of the two assessment methods results in a effective discrimination between different level oils. Results of interlaboratory tests concerning European reference oils for gasoline and diesel engines are given (Table 7 and Figs. 3 and 4). - An improvement of a coking test on an inclined plate (Figs. 6 and 7), in which a given volume of oil flows as a thin film over a stainlesssteel plate heated to a very high temperature. The deposits formed at the end of testing are evaluated according to their nature (carbon or varnish), their amount and also according to the principles of the CEC rating method (Figs. 8 and 9). Likewise, a system of video rating of microcoking plates by color recognition is described (Figs. 11 and 12). This system, called Video-Cotateurcan accurately reproduce the visual rating (Fig. 13) while eliminating the subjective factors of this rating. The results obtained with this system make up the first phase in the route to the computer-assisted rating of engine parts (Fig. 14).

Introduction: Data concerning the clinical and therapeutic characteristics of patients with schizophrenia treated by antipsychotic in naturalistic conditions are useful. Two national pharmacoepidemiological studies were conducted in France, a retrospective survey RÉALITÉ and a prospective study RÉALITÉ LT, to examine the use of loxapine, first in acute and chronic psychotic states and second in long-term treatment prescribed for patients with schizophrenia., Aim of Study: The aim of RÉALITÉ LT is to specify the clinical characteristics of schizophrenic patients treated by loxapine for at least 4 months and the description of the methods of use of this antipsychotic medication during a 6-month follow-up in "real life" conditions., Design of Study: RÉALITÉ LT is an epidemiologic, observational, longitudinal, prospective (during a half-year period), multicenter and national study of the prescription of loxapine in routine clinical practice. For this study, 645 patients with schizophrenia treated by loxapine were recruited, assessed by PANSS, CGI, GAF, MeDra-SOC-PT for side effects and Girerd questionnaire for compliance; statistical analysis used SAS 9.2., Results: Six hundred and forty-five adult patients were included and assessed at inclusion, month 3 and 6. These patients were mostly male (69%), with an average age of 41, inactive (68%), lonely with no child (79%), under psychiatric care for more than 5 years (81%), less than one third were inpatients. The subtypes of schizophrenia were paranoid (59%), disorganised (21%), undifferentiated or residual (10%), the outcome of psychotic illness was episodic (50%) or continuous (33%). The daily mean dosage of loxapine was 168,4 mg/d, in antipsychotic loxapine monotherapy (27%) or in combination with other antipsychotics (63%); it was often associated with psychotropic medications (anxiolytic [72%], antidepressant [21%], normothymic [19%]). The stability of the dosage of loxapine during the 6 months follow-up (60%) was associated with strict loxapine monotherapy or antipsychotic monotherapy (loxapine associated with other psychotropic medication). Safety, side effects and compliance were compared with previous studies., Discussion and Conclusion: These results are discussed, comparing the two pharmacoepidemiological studies RÉALITÉ and RÉALITÉ LT, loxapine is used in compliance with the two indications (smpc) and French guidelines (HAS, Haute Autorité de santé)., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

A retrospective observational pharmaco-epidemiological survey was conducted during 24 weeks between October 2004 and March 2005 in metropolitan France (384 investigators) to more clearly define the use of loxapine in acute and chronic psychotic states. The objective of this national survey was to specify the clinical and therapeutic profile of patients managed by this antipsychotic in two cohorts of adult patients: one in "acute phase" (prescription of loxapine during the previous 4 weeks), the other in "maintenance phase" (prescription of loxapine for more than 8 weeks). The two groups of the recruited population (1,511 patients) presented identical sociodemographic data. Selection criteria were adapted to the data collected to ensure statistically relevant analysis: 696 patients in acute phase and 633 patients in maintenance phase. The acute phase group was predominantly composed of known patients (82% of patients had a psychotic history) with schizophrenia (47%) or mood disorders (57%) who had already presented acute episodes (an average of 5.4). The current episode consisted of a state of agitation (88%) lasting an average of two weeks, requiring hospitalization (87%), scheduled admission [HDT (admission at the request of another person) in 47.5% of cases and HO (statutory admission) in 40.8% of cases] and prescription of loxapine monotherapy (56%) at a mean daily dose of 177,3 mg. The maintenance phase group comprised a population of known patients (87.5%), schizophrenics (63%), presenting psychotic symptoms (dissociation 82%, delusions 74%) or mood disorders (71%) requiring voluntary hospitalization (78%) for a mean duration of 180 days and a prescription of loxapine monotherapy in 28% of cases at a mean daily dose of 131.6 mg. The loxapine-haloperidol combination (21%) was prescribed more frequently in the second group in the case of chronic disorders; in the other cases, loxapine was coprescribed with the main second generation antipsychotics: risperidone (16%), olanzapine (16%), amisulpride (11%). CGI assessment of the overall study population revealed a marked or very marked clinical improvement with no significant adverse effects in more than 80% of cases.

The C(17,20)-lyase is a key enzyme in the biosynthesis of androgens by both the testes and adrenals. A complete inhibition of this enzyme would provide an alternative means of androgen suppression for the treatment of prostatic cancers. In the present study, the inhibitory effects of new non-steroidal compounds were tested in vitro on rat C(17,20)-lyase versus abiraterone, a reference steroidal inhibitor. Their activities were also evaluated in vivo on plasma testosterone (T) and luteinizing hormone (LH) levels and on testes, adrenals, seminal vesicles (SV) and ventral prostate (VP) weights after 3 days of oral treatment to adult male rats (50mg/kg per day p.o.). Inhibition in the nanomolar range was obtained with TX 977, the lead racemate product in this series, and optimization is ongoing based on a slight dissociation observed between its two diastereoisomers, TX 1196-11 (S) and TX 1197-11 (R). These non-steroidal compounds (including YM 55208, a reference competitor) proved to be more active in vivo than abiraterone acetate in this model, but the observed impact on adrenal weight suggests that the specificity of lyase inhibition versus corticosteroid biosynthesis deserves further investigations with this new class of potentially useful agents for the treatment of androgen-dependent prostate cancer.

The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo. They proved to be strong inhibitors of estrone sulfatase when measured on the whole human JEG-3 choriocarcinoma and MCF-7 breast cancer cells and their IC(50)s found to be in the range of known standard inhibitors. Their residual estrogenic activity was checked as negative in the test of induction of alkaline phosphatase (APase) activity in whole human endometrial adenocarcinoma Ishikawa cells. In addition, their effect on aromatase activity in JEG-3 cells was also examined, since the goal of inhibiting both sulfatase and aromatase activities appears very attractive. However, it has been unsuccessful so far. Then, in vivo potencies of TX 1299, the lead compound in our chemical series, were evaluated in comparison with 6,6,7-COUMATE, a non-steroidal standard, in two different rat models and by oral route. First, the absence of any residual estrogenic activity for these compounds was checked in the uterotrophic model in prepubescent female rats. Second, antiuterotrophic activity in adult ovariectomized rat supplemented with estrone sulfate (E(1)S), showed that both compounds were potent inhibitors, the power of TX 1299 relative to 6,6,7-COUMATE being around 80%. This assay was combined with uterine sulfatase level determination and confirmed the complete inhibition of this enzyme within the target organ. Preliminary studies indicated that other non-steroid compounds in the Théramex series were potent in vitro and in vivo inhibitors of estrone sulfatase in rats and further studies are in progress.