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RESUME La precarite est l’incapacite des individus a jouir de leurs droits fondamentaux, en particulier dans le domaine de la sante. Pauvrete et precarite sont intimement liees. Il y a en France environ 9 millions de personnes vivant au-dessous du seuil de pauvrete, dont 3 millions d’enfants, 140 000 personnes vivant a la rue (les « SDF »). La France accueille chaque annee 200 000 migrants, en Ile de France 35 000 personnes sont hebergees chaque nuit dans des hotels ou des dispositifs dedies. Parmi les plus precaires, la mortalite et la morbidite sont augmentees. Le taux de couverture vaccinale est inferieur parmi les enfants issus de familles pauvres, la participation aux depistages des cancers depend de facteurs socio-economiques, les campagnes de prevention sont d autant moins efficaces que le niveau de revenus est bas. L’acces aux soins et a la prevention de certains sous-groupes de la population est particulierement difficile : personnes vivant a la rue ou en grande precarite, personnes hebergees a l’hotel par le Samu social (115), prisonniers, gens du voyage, migrants... De tres nombreux dispositifs sanitaires et sociaux ont ete developpes a destination des populations precaires : Aide medicale d’Etat, Couverture maladie universelle complementaire, Aide complementaire sante, Equipes mobiles psychiatrie precarite, Permanences d’acces aux soins de sante, Plan pluriannuel de lutte contre la pauvrete et pour l’inclusion sociale, Programmes d’acces a la prevention et aux soins geres par la Agences regionales de sante, etc. De nombreuses associations humanitaires sont actives dans le champ de la sante. Malgre le deploiement de moyens importants, la situation sanitaire des personnes precaires et pauvres est de plus en plus preoccupante. De nouvelles initiatives doivent etre encouragees pour que la sante ne reste pas une preoccupation secondaire pour les pauvres et les precaires, pour ameliorer le bien-etre des « exclus de la sante », pour favoriser la prevention. Des efforts particuliers doivent concerner les populations les plus vulnerables : chomeurs, personnes âgees, femmes enceintes et enfants, familles monoparentales et malades en situation de precarite, migrants, exclus sociaux, en facilitant l’acces aux mesures deja existantes, en adaptant leur large panoplie a la mosaique des situations qui existent, en les coordonnant de facon efficace, en developpant de nouveaux moyens facilitant l acces a la sante. Des mesures appropriees sont recommandees concernant la coordination des actions dans ce domaine, la facilitation de l acces aux droits, le recours a des technologies facilitatrices, le deploiement cible des richesses de notre systeme de sante. L integration de ces specificites contribuera a faire de la sante un droit pour tous et a ce qu ’il existe moins de personnes exclues de la sante. La coordination des dispositifs europeens doit etre renforcee.

Summary Background The effect of oxygen on markers of oxidative stress has not been totally elucidated because previous studies have yielded conflicting results. Methods A method for the collection and gas chromatography-mass spectrometry of the halogenated volatile organic compounds in human alveolar breath is described. A transportable apparatus sampled specifically alveolar breath; the volatile organic compounds were captured in a thermal desorption tube, Carbotrap 200®. The sample was thermally desorbed from the trap in an automated gas chromatography with mass spectrometry detection and peak fragmentation. Compounds were identified by reference to a computer-based library of mass spectra. Results Trichlorotrifluoroethane, tetrafluoroethane, dichlorodifluoromethane were identified in alveolar breath of healthy volunteers after mental exercise-induced oxidative stress. The effects of halogenated alkanes were investigated on electron transport chain activity. These agents impaired the NADH oxidation suggesting an inhibition of the complex I (NADH: ubiquinone oxidoreductase) of the electron transport chain. These inhibitory effects are suspected likely to fight against oxidative stress deleterious reactions. Conclusion Chemical inhibition of the oxidative burst in human body trough these halogenated inhibitors is a new concept of significant practical, medical, biological and scientific interest.

The effect of oxygen on markers of oxidative stress has been partially elucidated. Volatile organic compounds (VOCs) are created during the oxidative burst and excreted in the human alveolar breath, which indeed contains biomarkers. A general concept including collection, separation, detection and clinical biomakers validation is presented in this article: (i) a method for the collection and GC-MS of halogenated VOCs in human alveolar breath is described: a transportable apparatus which sampled specifically alveolar breath; the VOCs were captured in a thermal desorption tube, Carbotrap 200® and each sample was thermally desorbed from the trap in an automated GC-MS apparatus; (ii) the inhibitory effects of halogenated alkanes on mitochondria are suspected likely to fight against oxidative stress deleterious reactions; (iii) two-dimensional gas chromatography occurs by the repeated and re-injection of effluent from one chromatographic column into a second column of orthogonal phase. A new commercial GCxGC system is presented; it is accomplished with a dual-stage, quad-jet thermal modulator positioned between the two columns; (iv) the affinity-based sensors usually used in connection with the GCxGC system face a difficulty to take into account different biases coming from different sources of drifting. Compared to other affinity-based sensing modes like electrical ones, gravimetric sensors enable a better decoupling. Nano Electro Mechanical Systems (NEMS)-based resonators are a particular type of gravimetric gas sensors. They are coated with a sensitive layer of polymer where gases of interest present in the atmosphere adsorb, generating an additional mass load which is measured through a frequency shift; (v) examination of exhaled breath has the potential to change the existing routine approaches in human medicine. Breath sampling to identify volatile biomarkers in diseases has been proposed in several respiratory diseases. Several VOCs have been identified in these patients by GC-MS. However, the use of traditional analytical instruments such as GC-MS to detect biomarkers of diseases has not become a routine for clinical applications. Consequently the electronic nose was the logical instrument of choice for disease diagnosis due to the capability of identifying complex mixtures of VOCs (as a whole) within sampled air using pattern-recognition algorithms.

Resume La realisation des essais cliniques se fait dans un cadre reglementaire strict. L’objectif de cette table ronde etait d’elaborer des recommandations raisonnables pour la mise en œuvre des bonnes pratiques cliniques (BPCs) dans certains types de recherches, compte-tenu de leurs caracteristiques et enjeux. Deux types de risque a prendre en compte ont ete identifies: ceux lies aux caracteristiques de la recherche et ceux lies a l’impact des resultats de la recherche. Une grille d’evaluation de ces risques a ete elaboree. Les travaux de la table ronde se sont articules autour de 3 thematiques principales: l’adaptation du monitoring, le medicament experimental, les effets indesirables. Trois methodes d’adaptation du monitoring ont ete passees en revue avec liste des avantages et inconvenients: l’approche graduelle, le monitoring centralise, le monitoring par sondage. La reflexion sur le medicament experimental s’est organisee autour du circuit du (des) medicament(s). L’arbre decisionnel « de base » suivant est recommande: 1) le medicament est-il experimental ? 2) la conception et les objectifs de l’essai necessitent ils un conditionnement specifique a la recherche ? 3) le risque d’utilisation est-il superieur a celui de la pratique courante ? Enfin, il est apparu que l’adaptation de la mise en œuvre des BPCs en terme de pharmacovigilance etait tres limitee et qu’ elle pouvait eventuellement se concevoir pour le medicament, objet de la recherche, qui a deja une autorisation de mise sur le marche (AMM) et dont le profil de securite est bien connu; dans ce cas, seule une simplification du recueil des evenements indesirables non graves est envisageable, qui peut se faire via l’elaboration et l’utilisation de listing standardise de recueil. L’adaptation de la mise en œuvre des BPCs est possible. Elle doit tenir compte des caracteristiques de la recherche : quels objectifs/quels risques/quels enjeux. Les choix en terme d’adaptation doivent etre predefinis, documentes et justifies; si necessaire ils seront aussi reevalues en cours d’etude.

The conduct of clinical trials falls within a strict regulatory framework. The objective of the round table was to develop reasonable recommendations for the implementation of GCP according to the type of research and taking in account the risks and challenges related to this research. Two types of risks have been identified: those related to the characteristics of the research and those related to the impact of the study results. The group designed an evaluation table of these risks. The round table focused its investigations on 3 main themes: monitoring, the investigational medicinal product and undesirable effects. Three methods of monitoring adaptation were analysed in terms of advantages and disadvantages: the gradual approach, the central monitoring, monitoring on the basis of sampling. Examination of the investigational medicinal product focused on the medicinal product circuit. The group recommends using the following 'basic' decision-making tree, which takes three elements into account: 1) is it an investigational medicinal product?, 2) do the trial objectives and design require packaging specific to the research?, 3) is the risk of use higher than that in standard practice? Finally, adaptation of the implementation of GCP in terms of pharmacovigilance appeared very limited and could possibly be considered for the medicinal product, the subject of the research, which already holds a marketing authorisation, and for which the safety profile is well known; in this case, only simplified collection of non-serious adverse events may be envisaged, which may be implemented by designing and using a standard collection listing. The adaptation of the implementation of GCP is possible. This firstly takes into account the characteristics of the research: which objectives/which risks/which challenges. The options in terms of adaptation must be pre-defined, documented and justified; if necessary, they will also be re-assessed in the course of analysis.

Les decouvertes de cibles therapeutiques et d'outils diagnostiques nouveaux sont aujourd'hui le fruit du developpement considerable de la biologie cellulaire et moleculaire et des biotechnologies. Apres le sequencage du genome humain, la pertinence des donnees obtenues par les techniques a haut debit, notamment celles issues de la genomique et de la proteomique, depend en premier lieu de l'assurance-qualite et de la tracabilite du materiel biologique a partir duquel sont effectuees les recherches, ainsi que des annotations qui qualifient les echantillons. Les Centres de Ressources Biologiques, qui incluent les biobanques, les cryobanques et les tumorotheques sont donc des infrastructures essentielles pour la decouverte d'outils innovants pour la prevention, le diagnostic et le traitement des maladies, et la mise au point de nouveaux medicaments. La constitution d'un reseau de Centres de Ressources Biologiques Humains sur des bases ethiques et juridiques harmonisees constitue aujourd'hui un enjeu majeur pour le developpement de la recherche medicale en Europe.

Resume Le sujet de la table ronde etant initialement tres vaste, il avait ete convenu avec les participants de le recentrer sur les therapies cellulaires (TC) impliquant des cellules autologues utilisees dans des situations de reconstruction tissulaire, d’immunomodulation et de transduction. La TC autologue concerne aussi bien des pratiques tres innovantes que des produits utilises en routine depuis plusieurs annees. Le cadre reglementaire de la TC est maintenant finalise en France. Ce dernier met en exergue le fait qu’un produit de TC est intrinsequement lie a son procede de preparation. L’objectif de cette table ronde etait de definir les pre-requis indispensables a prendre en compte lors du developpement de therapies impliquant des preparations cellulaires ex vivo et ce, afin de s’assurer de la securite d’emploi de tels produits. Les differentes etapes du developpement d’un produit de therapie cellulaire (PTC) ont ete envisagees : (i) contraintes de production permettant de garantir la qualite du produit ; (ii) developpement non clinique : importance de modeles animaux pertinents pour demontrer la preuve du concept et affiner les specifications du PTC ; (iii) developpement clinique : specificite methodologique du developpement d’un PTC. Les problemes inherents a l’utilisation des produits therapeutiques annexes (PTA) au cours du developpement d’un PTC ont ete souleves. Des mesures ont ete envisagees pour qu’a terme l’approvisionnement et la qualite d’un PTA ne constituent pas des facteurs limitants pour le developpement de la TC en France. Enfin, une information des professionnels de sante et des industriels concernant la biovigilance s’est averee necessaire.

The topic of the round table being very broad, it was agreed with the participants that the discussion should be focused on autologous cell therapy (CT) used in tissue repair, immunomodulation or gene transduction. Autologous CT is actually comprised of both very innovative procedures as well as of products used in routine clinical practice. In France, the regulatory framework for CT has now been finalised, underlining the fact that a CT product (CTP) is intrinsically linked to the process used in its preparation. The objective of this round table was to define the essential prerequisites for the development of therapies involving ex vivo cell preparations and, more specifically, to address the issues associated with patient safety during the course of product development. The different stages of CTP development were considered: (i) requirements for CTP manufacturing in order to guarantee product quality; (ii) nonclinical development, and selection of appropriate animal models to provide the proof of the concept and support the definition of CTP specifications; and (iii) clinical development and methodological specificities of CTP development. The specific problems associated with the use of ancillary therapeutic products (ATPs) during the development of a CTP were discussed. Actions were proposed to ensure long-term supply of ATPs, which may be a significant bottleneck for the development of CT in France. Eventually, new regulatory provisions will come into force in the area of biovigilance, and it was deemed necessary for healthcare and industry professionals to be appropriately involved in the implementation phase.

There is evidence that exhaustive exercise produces depression of the immune system, especially on the number and activity of Natural killer (NK) cells. On the other hand, fermented milk has been shown to moderate the immune response by inducing NK activity. The present work was carried out to determine if a Lactobacillus casei (LC) fermented milk supplemented diet would provide protection of the immune system against an exercise induced immune system depression of NK cells. Twenty‐five athletes were selected out of 94 for their significant decrease in NK cell concentration compared with a normal basal concentration in plasma 2 h after an exercise stress test. Subjects ingested a daily fermented milk diet with LC for one month and a standard milk diet also for one month. After each phase of dieting, a subject was investigated before, 5 min and 2 h after an exercise stress test, testing for NK cells and IL‐1β IL‐6, IL‐2, IFNγ, IgA, IgM, IgG, NK cells, CD8, CD4, CD3 and sIL‐2 receptor. A significant smaller...

Continuing advances in life sciences and medical research are the result of the remarkable achievements of cell and molecular biology. In the post-sequencing era, the quality of the huge amount of data continuously generated by biotechnology, i.e. genomics, proteomics and high-throughput screening, depends on the quality assurance and the traceability of the original biological materials, including the annotations linked to these materials. Thus, biological resource centres are key infrastructures supporting biotechnology, bioprocessing and the development of new approaches in the prevention, diagnosis and treatment of diseases.

Ceramides and distearoylphosphatidylcholine (DSPC) were incorporated in various liposomes preparations in comparison with dipalmitoylphosphatidylcholine alone. Preparations were introduced in an ‘Artificial Stomach-Duodenum’ model to improve their stability. Better results were observed for DSPC and ceramide-containing liposomes. Entrapment of CuZn Superoxide dismutase (SOD) in liposomes have been carried out for oral administration. The efficiency of entrapment of SOD was 35.4% for liposomes without ceramides, and from 24.3% to 46.1% for ceramide-containing liposomes.

A method for the preparation of soft capsules (Gl.C) and chewable gums (GCG) of the hydrophobic wheat protein, crude gliadin, is reported. Gliadin films were found to be more hydrophilic than comparable gelatin films. The release of paracetamol was significantly sustained, indicating drug delivery. Drug release profiles in 0.1 M hydrochloric acid media consisted of three regions for Gl.C: these were an initial latency period, followed by a low release region and essentially constant rate; and one region for GCG with very slow release of paracetamol. A mechanism of drug release is proposed involving hydrophobic interaction between gliadin and non-polar ligands. These results are discussed and based on this study, gliadin appears to be a highly promising, low-cost, bioacceptable protein for the manufacture of drug formulations with a very interesting controlled released potency.

Resume La formation de radicaux libres et la peroxydation lipidique sont des mecanismes a l'origine de dommages cellulaires. La peroxydation des acides gras polyinsatures, tels que l'acide linoleique et l'acide linolenique, qui sont tous les deux des composes des membranes cellulaires, induit la formation de pentane elimine par l'air pulmonaire. Cet hydrocarbure volatil est considere comme un marqueur satisfaisant de la peroxydation lipidique. Les auteurs ont mis au point et valide une methode non invasive utilisant l'adsorption et la concentration des echantillons gazeux sur des cartouches constituees de differents carbones graphitises, avec desorption thermique et dosage par chromatographie en phase gazeuse. Les auteurs presentent egalement l'interet du dosage de ce marqueur dans differentes conditions physiopathologiques telles que: le vieillissement, l'exercice physique, le stress, l'agression chimique, l'irradiation.

The aim of this study was to improve the administration form of the oropharyngeal decontaminating mixture manufactured at the “Pharmacie Centrale des hopitaux de Paris”. Natrosol 250 HHX Pharm ® was selected to prepare a powder meant to be dispersed in the buccal cavity, become a bioadhesive in situ and form a gel with saliva. A test of in vitro bioadhesion was used to select the best Natrosol 250 HHX Pharm ® ratio. A test of ex vivo bioadhesion, on bovine sublingual mucous membrane, permitted us to compare the actual gel form with powder and granular forms and to demonstrate a progressive release of the drugs from the granular form.

A reversed phase high-performance liquid chromatography method was developed to separate amino acids contents in total parenteral nutrition solution and peptides in enteral mixtures. Retention is attributed to hydrophobic interactions between the solutes and the hydrocarbonaceous functions covalently bound to the stationary phase surface. Consequently, the analytes were eluted in the order of their increasing hydrophobicity. The mixtures were analyzed by using gradient elution with increasing content and monitoring the column efiuent at 210 nm. composition (23), it seems that peptidic bound plays a crucial role in the retention of peptides. In order to solve the cited separation problems, il seems that the high selectivity of the ligand exchange procedure combined with the high efficiency obtained with the silica microparticles made ligand exchange copper (II) chromatography offers an interesting alternative. Further studies on this field are being carried out.

An over-pressure layer chromatography (OPLC) method for the separation and quantification of quinine, quinidine and hydroquinidine is discussed in this paper. After the development with the mobile phase methanol-acetonitrile-ammonia 0,2M (130: 68 : 2, v/v), a densitometric detection was performed by the fluorescence emission (excitation wavelength = 348 nm; emission wavelengh = 420 nm). This technique is simple, fast and adapted to small series of determination for the quality control and therapeutic drug monitoring.

An over-pressure layer chromatographic procedure with photodensitometric detection for the simultaneous determination of water-soluble vitamins in multivitamin pharmaceutical preparations was developed and evaluated. The method uses high-performance TLC (HPTLC) plates with silica gel as the thin-layer, and an n-butanol:pyridine:water mixture (50:35:15, v/v/v) as mobile phase at a rate of 0.25 mL/min for baseline separation. The quantitation was carried out without derivatization (vitamin B1, vitamin B2, vitamin B6, folic acid, nicotinamide, vitamin C) or after spraying ninhydrin reagent (calcium pantothenate) or 4-dimethylaminocinnamaldehyde (vitamin B12, biotin). This was applied to the analysis of multivitamin solutions. Satisfactory relative standard deviations and good recovery were obtained for all the vitamins examined. It was concluded that this method is fast, accurate, specific, and suitable for routine quality control use.

The kinetic behaviour of bovine erythrocyte Cu-Zn SOD was investigated in Sprague Dawley male rats after subcutaneous and oral administrations of doses ranging from 0 center dot 5 to 20 mg kg-1. Studies have been carried out with SOD and SOD encapsulated into liposomes containing or not containing ceramides. The maximum concentration (Cmax) in blood cell pellets ranged from 8 center dot 65 to 11 center dot 03 U/mg haemoglobin (Hb) after subcutaneous injection, and from 4 center dot 48 to 8 center dot 23 U/mg Hb after oral administration. The maximum concentrations were reached in 5 h (t max) for the two routes. Comparison between the areas under the curves (AUCs) obtained after subcutaneous and oral administration allowed the calculation of relative bioavailability (F'). The maximum bioavailability after oral administration was 14% for free SOD, 22% for SOD encapsulated into liposomes, and 57% when ceramides were added to liposomes. Poor SOD bioavailability was enhanced by liposome encapsulation, and ceramide addition seemed to be beneficial for oral encapsulated SOD administration.

Substantial evidence supports the theory that free radicals, especially oxygen radicals, are involved in the process of aging. The human organisms have two ways to fight them: an enzymatic way with enzymatic intervention like superoxide dismutase, catalase... and a chemical way with the intervention of scavengers such as vitamins, cysteine, methionine, gluthatione... The aim of this work was to determine that an intakes of vitamins association: vitamin E, vitamin C and beta carotene induce an increase of singlet oxygen protection of erythrocytes' subjects. The method was based on the haemolytic effect of singlet oxygen which is generated by irradiation of hematoporphyrine at 365 nm, in 22 p. cent suspension of erythrocytes' subjects. Results show that a supply of beta carotene (15 or 30 mg/day), vitamin E (15 mg/day) and vitamin C (30 mg/day) involves an increase of singlet oxygen protection of erythrocytes of subjects. This protection appears very quickly after 15 days of treatment.

A large body of evidence indicates that AIDS may be the consequence of a virus-induced antioxidant deficiency and implicates reactive oxygen species (ROS) in the pathogenesis of HIV infection. The high level of antigenic acid and cytokines activities in AIDS results in the production of superoxides (O2-), hydrogen peroxide (H202) and hydroxyl radicals (OH). HIV-infected T cells display low levels of SOD, catalase, thioredoxin and glutatione peroxidase rendering them susceptible to undergo apoptosis. Induction of NF kappa B and HIV replication are at least in part dependent on reactive oxygen intermediates. We examined the protective effects of two antioxidants. Ferulic Acid (FA) and Ethyl Ferulate (EF) at 1, 5, 10, 10 microM on the TNF induced HIV activation in the chronically infected promonocytic U1 cell line. FA and EF at 5 microM elicit a marked decrease of HIV p24 release. HIV inhibition was greater after pretreatment with EF than with FA. At these concentrations, no cytotoxicity was observed. When SOD (100 UI) was combined with EF and FA no more inhibition was observed. But when SOD was added alone, it induced a marked inhibition (30%). This class of drugs may present potential interest as antiviral agents or as adjuvant therapy in AIDS.

Epidemiological and experimental studies suggest that dietary milk products may exert an inhibitory effect on the development of several types of tumors. Some recent experiments in rodents indicate that the antitumor activity of the dairy product is in the protein fraction and more specifically in the whey protein component of milk. It has been demonstrated that whey protein diets result in increased glutathione (GSH) concentration in a number of tissues, and that some of the beneficial effects of whey protein intake are abrogated by inhibition of GSH synthesis. Whey protein is particularly rich in substrates for GSH synthesis. It has been suggested that whey protein may be exerting its effect on carcinogenesis and VIH infection by enhancing GSH concentration. Lactoferrin, one of the proteins contained in whey has aise been studied in this way. It has been suggested that lactoferrin binding may play an important role in maintaining, optimal mononuclear phagocyte function, thus protecting adjacent tissue against phagocyte derived radicals. Moreover it has been demonstrated by one of us that the level of plasma lactoferrin were decreased in HIV-1 infected patients in relation to the progression of the disease. The aim of the present study is to evaluate in rat the reactive oxygen species, scavenger activities (ROSSA) of red blood cells (RBCs) with a multifermented whey (SK 344), by repeated doses during 16 days. This study has permitted to demonstrate in vivo that the SK 344 has an excellent ROSSA corresponding to a limitation of the lipoperoxidation of RBCs membranes by singlet oxygen and nitric oxide. We can conclude that whey protein, lactoferrin and multifermented whey are good candidates as dietary inhibitors of the oxidative stress and should be considered as potential medicinal foods in various pathologies as HIV infection and cancer.

Toxic reactive oxygen species (ROS) generated by mononuclear phagocytes and neutrophils by means of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system can produce, by chain reaction, a wide array of molecular alterations including lipid peroxidation. Pentane measurements in alveolar air breath, which can be considered as a specific marker of lipoperoxidation, are performed in Humans affected by immunodeficiency virus (HIV) which is characterized in its course by a progressive CD4+ lymphocytes depletion including reduced production of regulatory cytokines and oxidative burst. Pentane measurements are carried out after collection of the alveolar air breath on graphite cartridges followed by thermal desorption and gas chromatographic separation of alkanes. The 7 first patients show a mean value of 5.73 nmol/1 of pentane.

Resume L'oxydation vanadique de dimethoxy-6,7 isoquinoleines substituees en 1 a montre le role essentiel que jouent les carbones situes en α d'un heteroatome. La para chlorobenzyl-4 dimethoxy-6,7 isoquinoleine libre de tout substituant en ces positions, est ainsi sujette a une oxydation beaucoup plus poussee par le pentoxyde de vanadium en milieu sulfurique 5 M . En effet, la consommation molaire en ions vanadyle est, dans ce cas, nettement superieure a celle trouvee lors de l'oxydation des isoquinoleines substituees en 1. De plus, dans le milieu reactionnel ont ete isoles des produits tels que l'acide succinique et le dioxyde de carbone, temoins d'une oxydation profonde de la molecule.

Resume Afin de verifier la part prise dans l'oxydation vanadique respectivement par les groupements etheroxyde et le doublet electronique de l'azote de benzylisoquinoleines, les auteurs ont etudies l'oxydation sulfovanadique de l'iodomethylate de p -chlorobenzyl-4 dimethoxy-6,7 isoquinoleine. Dans le milieu reactionnel ont ete identifies des produits tels que les acides et aldehydes p-chlorobenzoiques, le chloro-4 phenyl-2 ethanone-2 ol-1, l'acide p-chlorophenyl-3 propionique, l'acide p-chlorophenyl-3 ceto-2 propionique, l'acide hydroxy-5 p-chlorobenzylidene-4 δ valerolactone-2 acetique et son ester methylique, et l'acide p-chlorobenzyl-3 methylamino-4 butene-2 oique. En tenant compte de la structure chimique de ces molecules, une hypothese de mecanisme reactionnel est proposee.

Pour le dosage du dioxyde de carbone et du monoxyde de carbone, des conditions operatoires sur l'etude du dioxyde de carbone ont ete reprises en partie et adaptees

Selenium stability in amino acid/dextrose/electrolytes/ascorbic acid/trace elements was evaluated by a specific and sensitive fluorimetric method of selenium(IV) determination. Ascorbic acid particularly with copper(II) ions, reduced selenium(IV) in selenium metal (Se). Cysteine present in amino acids solution induces complexation with selenium. The complex has been identified by high-performance liquid chromatography when cysteine and selenite are mixed in 4 1 molar ratio. The complex is releasing cystine and selenium(II). These reactions are responsible for the complete loss of selenium(IV) in total parenteral nutrition solutions.

An indirect UV detection method, using tetrabutylammonium hydroxide and papaveraldine perchlorate as counter ion and ion interaction reagent, respectively, is described. Water analysis and drug monitoring in the treatment of childhood epilepsy with bromides are presented as possible applications. As a result of analytical difficulties, a so-called “overload effect” was studied and a theoretical mechanism for this is proposed.

The degradation of the enkephalinase inhibitor thiorphan was studied. Liquid chromatography UV and electrochemical detections and several techniques of spectrometry showed that the degradation was oxidative and generates diastereoisomers of the corresponding disulfide. The degradation kinetics of thiorphan under different conditions of storage have been investigated by high performance liquid chromatography with UV detection. The influence of air, temperature, light and pH was studied. The combination of these factors enabled us to determine the optimal conditions of conservation and to propose a stable injectable form.

Resume Le controle de qualite des protheses nutritives fabriquees a l'hopital pose un probleme au pharmacien, en raison de l'absence, a la Pharmacopee, de monographie specifique concernant ces preparations. Les auteurs proposent quelques elements de reflexion permettant le choix de protocoles adaptes, tout en constatant l'impossibilite d'en realiser une analyse physicochimique et biologique complete avant utilisation. Il est recommande d'effectuer : 1) un controle preliminaire pour chaque formule, permettant d'examiner la compatibilite globale; 2) des controles en cours de fabrication, physicochimiques et biologiques, permettant de s'assurer de l'application des principes de bonne fabrication; 3) un controle succinct du produit fini. L'ensemble des essais proposes tient compte des moyens restreints dont dispose en general un hopital, mais qui peuvent permettre au pharmacien, meme dans ces conditions, de mettre a la disposition du corps medical une fabrication de qualite pharmaceutique.

A method using reversed-phase high-pressure liquid chromatography (with spectrometric detection at 218nm) is described for the determination in new pharmaceutical preparations (liposomes) of a new immunostimulating agent (N-acetylmuramoyl- l -alanyl- d -isoglutamine). Separation was achieved with a μ-bondapak column and phosphate buffer (pH 2.5)-methanol mixture (93:7 v/v) as eluent, at a flow-rate of 2 ml min . Sodium acetate was used as an internal standard. The detector response at 218 nm was linear in the range 10–170 μg ml . The method is simple and accurate.

Analyse du CO et du CO 2 dans une solution aqueuse. Le but de cet article est d'ameliorer la specificite d'autres methodes de detection

The oxidation, by vanadium pentoxide, of 1-substituted 6,7-dimethoxyisoquinolines has shown the essential part played by the carbon atoms located alpha to a hetero-atom. Thus 4-(p-chlorobenzyl)-6, 7-dimethoxyisoquinoline is more readily oxidized by vanadium pentoxide in presence of 5M sulphuric acid than 1-benzyl-6,7-dimethoxyisoquinoline. Carbon dioxide and succinic acid have been identified amongst the oxidation products, and indicate more extensive oxidation of the molecule.

Sterile pharmaceutical preparations must be supplied to clinical wards; their high degree of safety is given by hospital pharmacists who are responsible for quality control of these preparations. Various considerations on the choice of protocol are suggested. Good manufacturing practice is to carry out quality controls at every stage of production of total parenteral nutrition fluids. However, these controls are made difficult by the poor equipment of hospital pharmacies and by the absence of specific pharmaceutical monographs. The selected protocol involves: preliminary controls, which determine the practicability of the suggested formulation, as well as its expiration date: amino acid determinations using liquid chromatography, electrolyte analysis and concentration, pH, evolution of particle size in fat emulsion according to storage conditions, choice of plastic container; microbiological controls: every two months and every time the pharmaceutical staff changes; moreover, a search for bacterial endotoxins using a chromogenic substrate (LAL technique) with "microstrips" is suggested; a sample from each admixture is kept under refrigeration for 15 days; controls during fabrication to check, at the end of the process, if good manufacturing practices have been realized: microbiological sampling of the working area and elaboration of a written procedure; control after fabrication of each nutrient admixture: determination of various elements such as sodium, potassium and dextrose in a 5 ml sample. These assays enable the checking of high standards of fabrication. Hospital pharmacies, despite their reduced equipment, can answer by these procedures to the physicians' needs and supply sterile TPN meeting pharmaceutical standards.

Due to the frequent use of essential oils and flavors (both natural and artificial), in the manufacture and formulation of patent medicines, the correct identification of these substances is an important area for pharmaceutical quality control laboratories.