Effects of a novel archaeal tetraether-based colipid on the in vivo gene transfer activity of two cationic amphiphiles.

Gene therapy for treating inherited diseases like cystic fibrosis might be achieved using multimodular nonviral lipid-based systems. To date, most optimizations have concerned cationic lipids rather than colipids. In this study, an original archaeal tetraether derivative was used as a colipid in combination with one or the other of two monocationic amphiphiles. The liposomes obtained, termed archaeosomes, were characterized regarding lipid self-assembling properties, macroscopic/microscopic structures, DNA condensation/neutralization/relaxation abilities, and colloidal stability in the presence of serum. In addition, gene transfer experiments were conducted in mice with lipid/DNA complexes being administered via systemic or local delivery routes. Altogether, the results showed that the tetraether colipid can provide complexes with different in vivo transfection abilities depending on the lipid combination, the lipid/colipid molar ratio, and the administration route. This original colipid appears thus as an innovative modular platform endowed with properties possibly beneficial for fine-tuning of in vivo lipofection and other biomedical applications.

Status Epilepticus Induced Spontaneous Dentate Gyrus Spikes: In Vivo Current Source Density Analysis.

The dentate gyrus is considered to function as an inhibitory gate limiting excitatory input to the hippocampus. Following status epilepticus (SE), this gating function is reduced and granule cells become hyper-excitable. Dentate spikes (DS) are large amplitude potentials observed in the dentate gyrus (DG) of normal animals. DS are associated with membrane depolarization of granule cells, increased activity of hilar interneurons and suppression of CA3 and CA1 pyramidal cell firing. Therefore, DS could act as an anti-excitatory mechanism. Because of the altered gating function of the dentate gyrus following SE, we sought to investigate how DS are affected following pilocarpine-induced SE. Two weeks following lithium-pilocarpine SE induction, hippocampal EEG was recorded in male Sprague-Dawley rats with 16-channel silicon probes under urethane anesthesia. Probes were placed dorso-ventrally to encompass either CA1-CA3 or CA1-DG layers. Large amplitude spikes were detected from EEG recordings and subject to current source density analysis. Probe placement was verified histologically to evaluate the anatomical localization of current sinks and the origin of DS. In 9 of 11 pilocarpine-treated animals and two controls, DS were confirmed with large current sinks in the molecular layer of the dentate gyrus. DS frequency was significantly increased in pilocarpine-treated animals compared to controls. Additionally, in pilocarpine-treated animals, DS displayed current sinks in the outer, middle and/or inner molecular layers. However, there was no difference in the frequency of events when comparing between layers. This suggests that following SE, DS can be generated by input from medial and lateral entorhinal cortex, or within the dentate gyrus. DS were associated with an increase in multiunit activity in the granule cell layer, but no change in CA1. These results suggest that following SE there is an increase in DS activity, potentially arising from hyperexcitability along the hippocampal-entorhinal pathway or within the dentate gyrus itself.

UV and visible light screening by individual sporopollenin exines derived from Lycopodium clavatum (club moss) and Ambrosia trifida (giant ragweed).

We have investigated the UV-visible light transmission of three types of micrometre-sized sporopollenin exine shells, two derived from Lycopodium clavatum (club moss) spores and one from Ambrosia trifida (giant ragweed) pollen. We have used spectrophotometer measurements of partial monolayers of exines and microscope absorbance imaging to derive the light transmission properties of individual exines. Measurements have been made for exines in air when light transmission losses are due to a combination of absorption, reflection and scattering processes and for exines dispersed in a liquid for which the refractive index (RI) is approximately equal to the RI of the exine such that reflection and scattering effects are negligible. Overall, it found that the light transmission of a single exine wall is approximately 50%. This value of the transmission is due mainly to light absorption, is similar for the three exines studied here and varies only slightly with light wavelength over the range 200-900 nm.

MRI contrast agent delivery using spore capsules: controlled release in blood plasma.

The exine coatings of spores can be used to encapsulate drug molecules. We have demonstrated that these microcapsules can be filled with a commercial gadolinium(III) MRI contrast agent (in this proof of concept study Gd-DTPA-BMA was used) which is slowly released in plasma due to enzymatic digestion of the capsule.