In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma.

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) fourteen days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo

Event Timing in Associative Learning: From Biochemical Reaction Dynamics to Behavioural Observations

Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca++ signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca++-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca++, depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems

Ostracods and fore-reef sedimentology of the Frasnian-Famennian boundary beds in Kielce [Holy Cross Mountains, Poland]

Four major microfacies have been recognized in the Psie Górki section and the bioclastic content indicates an open marine environment in the photic zone close to an algal shole. Sedimentological studies point to a regressive episode starting close to the Frasnian–Famennian boundary. The regressive microfacies pattern is revealed by the presence of semirestricted algal microbreccias that compose all of the lower part of the Famennian. The regression was accompanied by meteoric water invasion as the sea level fell. Seventy−six ostracod species are recorded. The ostracod assemblage, dominated by podocopids, belongs to the Eifelian ecotype and is indicative of a well−oxygenated marine environment below fair−weather wave base in the Frasnian part of the section, and of shallower environments in the base of the Famennian. No ostracod assemblage characteristic of hypoxic or semi−restricted water conditions has been recorded. The rate of extinction of ostracod species (>70%) close to the Frasnian–Famennian boundary is comparable with that known on the same level in several other sections investigated in the world. Five new ostracod species are proposed by J.−G. Casier and F. Lethiers: Selebratina vellicata, Samarella? minuta, Bairdiocypris ventrorecta, Acratia pentagona, and “Bairdia” psiegorkiensis

A preliminary study of the Ashgill carbonate beds from the lower part of the Fosses Formation (Condroz, Belgium)

The sedimentology and palaeontology of carbonate beds in the lower part of the Fosses Formation (Ashgill of the Condroz area, central Belgium) have been investigated. Two depositional interpretations are suggested: deposition either near a platform-ramp margin as bioclastic turbidites and interbedded shales or on a shelf as a transgressive sequence following a regressive event. Faunal affinities with the Baltic area and Wales are confirmed, and the location of Belgium in the tropics during the Ashgill is supported by the calcareous algae and the coral fauna. © 1993, Cambridge University Press. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe