Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes

Chlorohydroxyfuranones (CHFs) are mutagenic disinfection by-productsfound in chlorine-treated drinking water. In the current study,the genotoxicity of four CHFs, 3,4-dichloro-5-hydroxy-2(5H)-furanone(MCA), 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX), was determined. Two in vitro assays, the microscale micronucleusassay on L5178Y mouse lymphoma cells and the unscheduled DNAsynthesis assay on a hepatocyte primary culture from FisherF344 rats, were carried out. All four CHFs demonstrated genotoxiceffects in both assays. In the two systems used, CMCF was themost genotoxic compound, followed by MCA, MX and MCF, respectively.This work was the first study of the DNA damaging propertiesof all four CHFs in two in vitro genotoxicity tests. These newdata expand the range of genetic damages induced by this groupof compounds. ² To whom correspondence should be addressed. Tel: +33 3 20 8779 14; Fax: +33 3 20 87 73 10; Email: daniel.marzin{at}pasteur-lille.fr     

Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive -amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [³H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of -amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization.     

Safety of heparin-coated circuits in primates during deep hypothermic cardiopulmonary bypass

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Le cancer indépendant du psychisme: un manque d’interprétation créatrice?

Résumé: La recherche des liens entre les facteurs psychosociologiques et le cancer, tant en ce qui concerne l’étiologie de cette maladie que sa prise en charge et son évolution, n’a pas pour l’instant permis d’obtenir de résultats franchement significatifs, et ce malgré l’importance des efforts fournis. Cet article passe en revue les principales conclusions, mais, contrairement aux avis sceptiques qui prévalent dans la littérature médicale, il vise à dégager les pistes qui restent à explorer et qui demeurent prometteuses. Parmi elles, des recherches épidémiologiques chez l’enfant sont nécessaires, relativement aux événements de vie propres à cette tranche d’âge et en utilisant une approche systémique. Outre la survie, le confort et la qualité de vie et certaines caractéristiques comme l’anxiété, la dépression et le coping, de nouveaux objectifs devraient être envisagés pour évaluer l’impact des psychothérapies sur le cancer, entre autres en étudiant les variations des marqueurs principaux de l’immunité, des rythmes circadiens biologiques, du sommeil ou du cycle activité/repos. Les thérapies de groupe semblent avoir un effet principalement en raison des informations (médicales ou autres) dont elles permettent la communication, mais leur efficacité reste discutée. De nouveaux types d’intervention psychosociale devraient donc être introduits dans les essais, en raison de leurs effets rapides, dont certains prouvés sur l’immunité: par exemple l’hypnose. La psychologie clinique semble aussi bien adaptée à ce type d’étude. Les enfants, sous réserve d’une éthique satisfaisante, paraissent une cible privilégiée pour les recherches à venir, mais les essais doivent continuer à inclure des patients de tous âges et, ce, quels que soient le stade et le type de leur maladie. Enfin, sur le plan purement statistique, les analyses multivariées ont tendance à évincer les facteurs psychologiques quand leur pathogénéicité provient de conduites à risque (tabagisme, alcoolisme…) qu’ils favorisent. Les conclusions attribuant la responsabilité des cancers à ces seuls derniers facteurs (tabac, alcool) sont alors erronées. Au minimum, il faut réaffecter au facteur psychologique le poids de son influence sur l’exposition au carcinogène.