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Resume Objectif Decrire la methodologie de conception et de creation de SimUPAC 360°, parcours immersif de formation en realite virtuelle a 360° en unite de preparation des anticancereux. Methodes Un groupe de travail multicentrique (un centre hospitalier universitaire, un centre hospitalier et un centre de lutte contre le cancer) et interprofessionnel (pharmaciens, preparateurs en pharmacie hospitaliere, cadres de sante) a ete constitue. Le travail, base sur des visioconferences et un partage de documents en ligne, a ete decompose en six phases : choix du public cible et des objectifs pedagogiques, definition du business model, elaboration du scenario, tournage et montage, creation de l’outil pedagogique et enfin tests, ajustements et validation. Resultats Apres brainstorming, 77 erreurs ont ete proposees. Trois zones ont ete definies : sas d’habillage, zone de stockage/production et isolateur. Elles contenaient 15 erreurs parmi les 77 proposees et 20 points d’interet. Le tournage a ete realise sur 2 jours, dans 2 etablissements. Le montage a ete realise par un prestataire. Avant deploiement, l’outil a ete teste et valide par des experts. Discussion La constitution d’un groupe de travail multicentrique et interdisciplinaire, le choix du public cible, des objectifs pedagogiques et le business model permettent d’assurer la viabilite economique et la robustesse scientifique et technique. L’elaboration du scenario necessite de definir : zones d’activite puis, nombre, difficulte et typologie des erreurs. Conclusion La creation d’un outil de simulation numerique en sante necessite une methodologie rigoureuse et structuree. Elle permettra de decliner d’autres scenarios de formation.

Describe the process for designing and creating SimUPAC 360°, a virtual reality training in anti-cancer drug production units.A multi-centre (a University Hospital, a General Hospital and a Cancer Control Centre), inter-professional (pharmacists, hospital pharmacy technicians and health executives) working group has been set up. It was based on videoconferencing and online document sharing. The work was divided into six phases: choice of target audience and training objectives, definition of the business model, development of the scenario, shooting and editing, creation of the training tool and finally tests, adjustments and validation of the tool.After brainstorming, 77 errors were proposed. Three areas have been defined: covering area, storage and production area, and isolator. They contained 15 errors among the 77 proposed and 20 points of interest. The shooting was carried out over 2 days, in 2 hospitals. Assembly was carried out by a service provider specialist in real virtuality. Before to go online, the tool was tested and validated by experts.The establishment of a multi-centric and interdisciplinary working group, the choice of target audience, pedagogical objectives and business model ensure the economic viability and scientific and technical robustness of the tool. The scenario development requires to define: activity areas and then, number, difficulty and typology of errors.Creation of a virtual reality training requires a consistent and structured methodology. This methodology will make it possible to develop other training scenarios.

The acetalic photoreactivity of cyclic acetals was studied by some intramolecular acetalic hydrogen abstraction using photochemical ways (NORRISH. II type and BARTON - like reactions). The regioselectivities and stereoselectivities of these reactions were deduced from photochemical transformations of different tetrahydropyrannic cyclic ketoacetals, oxoalkglglycosides and hydroxyalkylglycosides. The abstraction of γ-acetalic hydrogen is not stereoselective by excited carbonyl groups but regiospecific to give lactones in good yields. With hydroxyalkyl hypoiodites, this γ-H abstraction is stereoselective to yield anomeric orthoesters with predominant retention of configuration. By δ-acetalic hydrogen abstraction, the photocyclization of oxoalkylglycosides leads to hydroxy spiro ketals with retention of configuration. The influence of differents substrates, of carbonyl substituents and temperature effects were described. In osidic series (gluco, manno, 2-deoxy), β-anomers are more photoreactive than α-ones. All these results can be interpreted using stereoelectronic effects at the acetalic center for the photocyclization reactions.

The process of sucrose esterification in the presence of a homogeneous catalyst was developed directing the reaction to the production of weakly substituted esters. Esterification of sucrose was processed with octanoyl chloride in a discontinuous reactor, in presence of 4-dimethylaminopyridine as catalyst. The process was operated in a time interval ranging from 0 to 80 min, at temperatures from 288 to 303 K, pH=10 and at atmospheric pressure. The following conversion levels were obtained: octanoyl chloride 11-84%, primary monoester production of 9-67%, secondary monoesters of 1.3-17%. Activation energies ranging from 158 l to 300 kJ/mol characterized the stages of the process, among them the stage of formation of the DMAP/RCOCl complex (162.43 kJ/mol). The increase in primary monoesters yield due to the temperature rise, leads to an increase in the rate of the direct reaction as well as in the speed of secondary monoester conversion to primary monoesters, quantifying a selectivity in primary isomers in the following positions sequence: 6> 1" > 6".

The comparative chemical oxidation of isomaltulose and methyl isomaltuloside is described using TEMPO or Pt catalysts.

Low temperature bleaching systems involving sodium perborate and an activator such as tetra acetyl ethylene diamine (TAED), with peracetic acid formation, are commonly used in Europe. Environmentally friendly bleaching agents such as carbohydrate derivatives (mono, oligo, anhydro saccharides, polyols and amino sugar acetates) could also be good products with bleaching activator properties. Correlation structure-reactivity was established; active acetyl groups were identified for each type of molecule in order to understand the effect of their nature and configuration, and to determine the role of neighbouring groups.

The comparative chemical oxidation of isomaltulose and methyl isomaltuloside is described using TEMPO or Pt catalysts.

The title tricyclic compound was obtained by photooxygenation of bis(5-formylfurfuryl) ether, followed by a dehydration reaction. The compound appears as a trans isomer, with respect to the relative positions of the lactonic rings to the dioxane ring, which remains chair shaped. Such a trans configuration has been found previously in anemonin, where the two lactonic rings are trans with respect to the cyclobutane ring

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail., 24 pages, 15 figures. submitted to Elsevier Preprint

The cytochrome P-450 (CYP) mediated hydroxylation of testosterone to 6 beta-, 7 alpha-, and 16 alpha-hydroxytestosterone (b beta-, 7 alpha-, and 16 alpha-OHT) and the dealkylation of ethoxycoumarin to 7-hydroxycoumarin (ECOD) and ethoxyresorufin to resorufin (EROD) were used to probe changes in CYP monooxygenase activities in liver microsomes from rats treated with the androgen receptor antagonist, zanoterone (Z). Phenobarbital (PB) and beta-naphthoflavone (beta-NF) were used as comparators. There were sex-related differences in the constitutive CYP activities and in the responses of CYP activities to Z. The greatest effect of Z administration was on 6 beta-OHT activity: It was increased up to 5.2-fold in males and 13.9-fold in females (Z high dose). The effect was larger than the produced by PB or beta-NF (or = threefold increases). Z (high dose), PB, and beta-NF increased ECOD to a similar extent, e.g., about 1.3-fold in males and 1.2-2.9-fold in females. beta-NF increased EROD (11.2-fold males, 6.2-fold females) more than PB (3.4- to 4.6-fold) or Z (1.3- to 1.7-fold). Since hydroxylation of testosterone at the 6 beta position in rats and humans is catalyzed primarily by CYP isoforms from the 3A subfamily, the increase in 6 beta-OHT suggests that Z induced CYP 3A activity. These findings were confirmed with Western immunoblots with probes for rat CYP 1A1, 2B1/2, 2E1, 3A, and 4A. Z produced a three-to fourfold increase in the 3A isoform for both male and female rats. Results from this study suggest that in a clinical setting, Z therapy has the potential to induce CYPs of the 3A subfamily and in so doing alter the metabolism and clearance of drugs that are substrates for the 3A subfamily.

The toxicology profile of new test compounds is ascertained in repeat-dose toxicity studies with exposure over 4 weeks or 3 months which yield a range between a high dose causing overt toxicity and a low dose with no observable (toxic) effect. In recent years, the immune system has been identified as a target of the direct toxic action of chemicals (Dean et al., 1989). A first step to the EU level to developed a test program to detected undesired effects on the immune system was undertaken in Luxembourg in 1984 (Berlin et al., 1987) . In consequence of this international activity, a number of collaborative studies were initiated. The aim of these studies was to select and validate available testing procedures in a tiered approach to find out their appropriateness of indicating adverse effects on the immune system after exposure to chemicals (Vos and vanLoveren, 1987; Hess et al., 1990). In a collaborative toxicity study initiated and coordinated by the Federal Institute for Health Prot ection of Consumers and Veterinary Medicine, four industrial laboratorys and one independent institute participated. The purpose of this study was to qualify and validate additional investigation (i.e., enhanced pathology, functional tests) within an ordinary subacute toxicity test protocol (Annex V, 67/548/EEC; OECD 407) to identify the effects of chemicals on the immune system during their regular safety evaluation.

The periodate oxidation of some derivatives of sucrose at primary positions is generally selective for the D-glucopyranoside group. A cleavage at C-2-C3 or C-3-C-4 positions was observed for the 6,1',6'-tri-O-trityl and 6,1',6'-tri-O-(tert-butyldemethylsilyl) derivatives, respectively. The periodate oxidation was more complete for all other derivatives with a cleavage at C-2-C-3 and C-3-C-4.

Resume Les glycols biprimaires lineaires peuvent etre employes comme donneurs dans la reaction de transfert catalytique d'hydrogene a des accepteurs comme la benzylidene acetophenone. Si la concentration de l'accepteur est faible, des reactions secondaires sont observees: reaction de dismutation pour les hemiacetals cycliques et processus de polymerisation pour les aldols lineaires et les dialdehydes. L'influence de la longueur de chaine des glycols sur ces reactions est discutee.

Alterations of the normal immune response were estimated in C57Bl/6 mice pretreated with cyclophosphamide, methylprednisolone sodium succinate, betamethasone sodium phosphate or cefoxitine as positive controls and three minor tranquillizers: dipotassium chlorazepate, diazepam and meprobamate. The specific immune response against sheep red blood cells (SRBC) was evaluated by numeration of the direct plaque-forming cells (PFC; humoral immunity) and by measurement of the footpad swelling (delayed-type hypersensitivity, DTH). In our experiments, the results with the positive controls were in the same order as those described by others, and at the dose levels used, these three minor tranquillizers did not really alter the specific humoral and cellular immune response against SRBC in the C57Bl/6 mice.

Effects of cysteine, phenolic acids, cinnamic acids, and of lyophilized malt and beer samples varying in their total content of polyphenolic compounds on the formation of N-nitroso compounds in vit...

Carbohydrate-bis-phosphinites of methyl-α-D-glucopyranoside and altropyranoside protected by benzylidene group in 4, 6-position lead to chelating ligands which are useful not only in asymmetric hydrogenation of prochiral aminoacid precursors, but also of prochiral ethylenic acids, producing in this latter case optical yields up to 54%.

A dipole moment analysis of the electric dipole moments of 2-formylfuran and 2,5-diformylfuran in solvents of low dielectric permittivity enabled us to determine the relative populations of the conformers, taking into account the relevant solvation energies of the species. Molecular orbital AM1-calculated enthalpies of all the conformers of 2-formyl- and 2,5-diformyl-furan are also presented and used in the discussion of experimental data.

α-Addition reactions of glycosyl isonitriles with primary and secondary amines allowed to prepare substituted glycosyl formamidines representing good precursors in the synthesis of nucleosides.

Benzalacetophenon (I) wird in Gegenwart von Rhodium- oder Ruthenium-Phosphin.-Komplexen durch Glucite zum gesattigten Vertreter (II) hydriert.