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Le voretigene neparvovec (VN) est la première thérapie génique en ophtalmologie indiquée chez des patients présentant une dystrophie rétinienne héréditaire liée à une mutation bi-allélique du gène RPE65. Sa récente autorisation européenne de mise sur le marché impose un cadre réglementaire et organisationnel strict pour son utilisation. Nous analysons ici les principales études ayant permis cette autorisation de mise sur le marché et décrivons les étapes nécessaires à déployer au niveau hospitalier pour une administration optimale chez le patient dans le cadre de la réglementation actuelle.

The efficacy and safety of an oral pentobarbital suspension for sedation during pediatric MR imaging were assessed.

Les dermatophytoses superficielles étendues résistantes aux traitements usuels peuvent être secondaires à des facteurs liés à l’hôte (immunodépression) ou à la souche (résistance). Nous décrivons le 1ercas en France d’une dermatophytose corporelle étendue résistante à la terbinafine (TBF) en lien avec une infection à une souche de Trichophyton mentagrophytes(T.m) porteuse d’une mutation du gène de la squalène époxydase (SQLE) et traitée efficacement par voriconazole topique.

Furan is an organic, volatile compound used in various chemical-manufacturing industries. Headspace gas chromatography is the analytical method of choice for obtaining reliable results on its occurrence. The presence of furan in some food items has been known since the late 1970s, but a US Food and Drug Administration (FDA) survey published in 2004 revealed the occurrence of furan in a broad variety of canned and jarred foods, including baby food, that undergo heat treatment. Furan is carcinogenic in rats and mice, showing a dose-dependent increase in hepatocellular adenomas and carcinomas. In rats, a dose-dependent increase of mononuclear leukaemia is evident and a very high incidence of cholangiocarcinomas of the liver, even at the lowest dose tested. There is evidence to indicate that furan-induced carcinogenicity is probably attributable to a genotoxic mechanism. However, chronic toxicity with secondary cell proliferation may indirectly amplify the tumour response. From the available data, there is a relative small difference between possible human exposure and the doses in experimental animals required to produce carcinogenic effects. However, reliable risk assessment requires further data on both toxicity and exposure. The European Food Safety Authority's (EFSA) Scientific Panel on Contaminants in the Food Chain (CONTAM) recommended these studies as part of a reliable risk assessment of furan in food.

Objectives: The aim of this study was to evaluate the toxicity of a new lipid complex formulation of amphotericin B (LC-AmB) produced by a simple process. Methods: Toxicity was evaluated after daily administration for 21 consecutive days in female CD1 mice. Doses of LC-AmB up to 20 mg/kg were used, and compared with Fungizone at 0.5 mg/kg and Abelcet at 10 mg/kg. Acute toxicity after a single bolus injection was also determined, as well as the haemolytic activity and toxicity to mouse macrophages in vitro. Results: LC-AmB reduced both the haemolytic activity of amphotericin B and its toxicity towards mouse peritoneal macrophages. Its acute toxicity (LD50 > 200 mg/kg in CD1 mice) was similar to that in the literature for the least toxic lipid formulations of amphotericin B. The relative liver weight increased slightly in mice treated daily with a dose of 20 mg/kg LC-AmB, as did the kidney weight in this group and the group treated with Fungizone. There was also a dose-dependent decrease in the haematocrit with all formulations. All treatments caused significant increases in transaminase levels. Total hepatic CYP 450 was slightly but not significantly increased in the groups treated with 20 mg/kg LC-AmB, Abelcet and Fungizone. However, expression of some isoforms of CYP 450 was reduced, the most marked being the hepatic CYP 3A1 after treatment with 20 mg/kg LC-AmB, Abelcet and Fungizone. The effects on hepatic function are probably related to accumulation in organs rich in phagocytic cells. Conclusion: LC-AmB did not induce any new toxicity compared with Abelcet and Fungizone.

Continuous recording of locomotion in an enclosed maze with no reinforcement other than that intrinsic to ambulation through the maze provided evidence for a dissociation between the efficiency of patrolling the entire maze and locomotor activity. Patrolling efficiency improved with repeated exposure to a single maze or to two similar maze configurations but not with daily presentation of dissimilar mazes. There were only small strain and sex differences in the development of efficient patrolling, whereas locomotor activity was considerably higher in female Roman high-avoidance (RHA) rats than in female Roman low-avoidance rats and higher in RHA female rats than in RHA male rats.Continuous recording of locomotion in an enclosed maze with no reinforcement other than that intrinsic to ambulation through the maze provided evidence for a dissociation between the efficiency of patrolling the entire maze and locomotor activity. Patrolling efficiency improved with repeated exposure to a single maze or to two similar maze configurations but not with daily presentation of dissimilar mazes. There were only small strain and sex differences in the development of efficient patrolling, whereas locomotor activity was considerably higher in female Roman high-avoidance (RHA) rats than in female Roman low-avoidance rats and higher in RHA female rats than in RHA male rats.

Separate groups of two different rat breeding lines, Roman High Avoidance (RHA/Verh.) and Roman Low Avoidance (RLA/Verh.), treated with either saline, nicotine (0.2 mg/kg), or amphetamine (0.4 mg/kg) were compared for exploratory efficiency and for exploratory locomotion by using two different mazes on alternate testing days. The RHA/Verh. rats generally showed more locomotion but less intermaze transfer of exploratory efficency than the RLA/Verh. rats. Nicotine did not alter exploratory efficiency but stimulated locomotor activity in the RHA/Verh. rats, while it did not significantly alter either category of behavior in the RLA/Verh. rats. Amphetamine stimulated locomotor activity in both rat lines but this stimulation was weaker in comparison with that of nicotine. In contrast to nicotine, amphetamine impaired exploratory efficiency in the RHA/Verh. rats. Like nicotine, amphetamine did not significantly affect exploratory efficiency in the RLA/Verh. rats. The results demonstrate that, when the two lines of rats are compared, there is a dissociation of the two categories of behavior and a further differentiation between nicotine and amphetamine effects.

A field study was performed to assess the level of drug residues in milk after therapeutic application of highly potent synthetic glucocorticoids. Dexamethasone was tested either as a crystalline suspension or as a combination of sodium phosphate and phenylpropionate esters. Intramuscular injection of these preparations in lactating dairy cows (60 μg dexamethasone/kg body wt) yielded drug residues in milk of up to 8.4 ng/mL 12 h after treatment. These dexamethasone residues fell to below 1.0 ng/mL within 3 days after treatment. Intramuscular injection of an aqueous flumethasone preparation (13.5 μg/kg body wt) produced drug residues in milk in the range of 0.7‐1.2 ng/mL 12 h after treatment, whereas flumethasone was below the detection limit of 0.23 ng/mL 2 days after administration. These results indicate that toxicologically significant residues may arise transiently in the milk during the first 2‐3 days after intramuscular injection of synthetic glucocorticoids. Urine from the same animals contained 5‐ to 50‐fold higher glucocorticoid concentrations than the corresponding milk samples. Thus, urine analysis appears to be an effective method to monitor the use of synthetic glucocorticoids in food producing animals.

L’association Ankyloblépharon-dysplasie Ectodermique-fente (Cleft) labio-palatine (syndrome AEC, MIM106260) est une forme rare de dysplasie ectodermique liée à une mutation hétérozygote dans le gène TP63codant la protéine P63 qui participe à la prolifération et à la différentiation épidermique. Outre les manifestations listées dans l’acronyme, les patients présentent, en période néonatale, des érosions cutanées, chroniques et douloureuses, localisées : scalp, dos, paumes et plantes. Le plus souvent, la guérison spontanée survient en 2 à 3 ans ; certains patients ne cicatrisent pas. Nous rapportons le traitement d’érosions chroniques grâce au repositionnement topique de PRIMA-1MET/APR-246, une molécule testée en cancérologie parce que régulatrice d’une protéine de la même famille que P63.

Verunreinigungen der Raumluft sind heute besonders zu beachten, da infolge verbesserter Abdichtung der Gebäudehülle zur Einsparung von Heizenergie die Zufuhr von Frischluft reduziert und dadurch die Luftqualität verschlechtert wird. Die häufigsten Verunreinigungen sind Tabakrauch, das radioaktive Edelgas Radon aus kristallinem Untergrund, Formaldehyd von Inneneinrichtungen und Isolationsmaterialien, Stickoxide vom Heizen und Kochen mit Gas sowie Lösungsmittel, die zum Reinigen verwendet werden. Gesundheitliche Gefährdungen entstehen vor allem durch Tabakrauch und durch Schadstoffe, die kontinuierlich von Inneneinrichtungen abgegeben werden. Diese Belastungen sind durch Begrenzung der Emissionen zu verhindern. Die Frischluftzufuhr zur Beseitigung der vom Menschen und seinen Aktivitäten stammenden Belastungen richtet sich nach der jeweiligen Belegung und Nutzung des Raumes. Sie sollte so bemessen sein, dass der Kohlendioxidgehalt 1500ppm nicht übersteigt. La viciation de l'air des locaux habités doit faire l'objet d'une attention particulière, car en raison de la meilleure isolation des maisons visant à économiser l'énergie calorifique, l'apport d'air frais est diminué et la qualité de l'air en est réduite. Les nuisances les plus courantes sont occasionnées par la fumée du tabac, radon, le gaz radioactif d'une couche cristalline, le formaldehyde contenu dans les revêtements intérieurs et les matières isolantes, l'oxide d'azote des chauffages domestiques et des cuisinières à gaz, ainsi que les dissolvants des produits de nettoyage. Les dangers menaçant la santé proviennent avant tout de la fumée du tabac ainsi que des substances nocives qui sont émises de manière continue par les revêtements intérieurs. Ces charges doivent être évitées par la limitation des émissions. Afin d'éliminer les nuisances dues à l'être humain et à ses activités, un minimum d'aération est nécessaire, celle-ci dépendant du revêtement et du degré d'utilisation de la pièce en question. L'aération devrait être mesurée de manière à ce que la teneur en dioxyde de carbone ne dépasse pas 1500ppm. In the last decade the significance of indoor air pollution to human health has increased because of improved thermal insulation of buildings to save energy: air turnover is reduced and air quality is impaired. The most frequent air pollutants are tobacco smoke, radioactive radon gas emanating from the soil, formaldehyde from furniture and insulation material, nitrogen oxides from gasstoves, as well as solvents from cleaning agents. The most important pollutants leading to health hazards are tobacco smoke and air pollutants which are emitted continuously from building materials and furniture. Such pollutants have to be eliminated by reducing the emission rate. A fresh air supply is necessary to reduce the pollutants resulting from the inhabitants and their activities, the amount depending on the number of inhabitants and the usage of the room. The carbon dioxide level should not exceed 1500ppm.

Résumé L'action de la nicotine et de l'amphétamine dépend des variables génétiques. Le nicotine stimule l'activité exploratrice, tandis que l'amphétamine produit un comportement stéréotypé.