[Anticonvulsant add-on therapy with Eslicarbazepine acetate : Results of the EPOS-study in adults in Germany]. / Antikonvulsive Zusatztherapie mit Eslicarbazepinacetat : Ergebnisse der EPOS-Studie bei Erwachsenen in Deutschland.

BACKGROUND: Due to inadequate seizure control achieved with antiepileptic drug (AED) monotherapy and the considerable side effects at high required doses, patients with partial-onset seizures (POS) often require AED combination therapy. Eslicarbazepine acetate (ESL) is licensed as an add-on therapy for POS and has a favorable tolerability profile. OBJECTIVES: To investigate retention, utilization, reported efficacy, safety and tolerability as well as effects on health-related quality of life using ESL as an add-on treatment to an established monotherapy in a real-world adult population with POS in Germany. PATIENTS AND METHODS: A subgroup analysis was performed on the data derived from the German study sites that had participated in an international, non-interventional, open-label study conducted in eight European countries (eslicarbazepine acetate in partial-onset seizures, EPOS). Adult patients with POS whose physician had decided to prescribe add-on treatment with ESL to an established monotherapy were followed over a total period of approximately six months (three visits: baseline and after periods of approximately three and six months). Data collection included patient retention, reported efficacy, safety and tolerability as well as quality of life (QOLIE-10). RESULTS AND DISCUSSION: The subgroup analysis included 104 patients which had been enrolled at 38 German study sites. After 6 months, retention of ESL add-on therapy was 86.5 %, with 44.7 % of patients reporting seizure freedom over the 3 months prior to this visit. The overall tolerability of ESL add-on therapy was favorable: 32 adverse events (AE) were reported in 20 patients (19.2 %), while only two events in two patients were considered serious. No new safety signals were detected.

Cage-like complexes formed by DOTAP, Quil-A and cholesterol.

In this note we describe the substitution of the phospholipid component in classical ISCOMs (immune-stimulating complexes) with the cationic lipid dioleoyl-trimethyl-ammonium-propane (DOTAP). The self-assembled colloidal structures formed by DOTAP, Quil-A and cholesterol were characterised using transmission electron microscopy and laser Doppler velocimetry. Samples were prepared using the lipid-film hydration and dialysis techniques. Cage-like structures containing DOTAP were obtained in high numbers using dialysis, but not lipid-film hydration on day 4 post-preparation. The formation of cage-like structures was however only observed at compositions with low weight proportions of DOTAP (less than 25%) resulting in neutral to negative zeta-potentials of the colloidal particles. Compositions with high weight proportions of DOTAP displayed phase separation phenomena. Thus, whilst DOTAP can be incorporated with Quil-A and cholesterol to form cage-like particles, it appears to be unsuitable to prepare cationic equivalents of ISCOMs.

On the dilution behaviour of immuno-stimulating complexes (ISCOMs).

Immunostimulating complexes (ISCOMs) are used as potent vaccine delivery systems. However, the mechanisms by which ISCOMs work are mostly unknown. The immunological potency of ISCOMs has often been associated with their characteristic cage-like structure. Since ISCOMs can be regarded as composite mixed micelles that contain Quillaja saponin as the surfactant, we postulated a micelle to vesicle transition of the particles upon dilution with aqueous solutions. The dilution behaviour of ISCOMs is not only an important preparative aspect, but may also be of high relevance for both cell culture and in vivo applications in which dilutions occur. Crude and purified preparations of ISCOM matrices were prepared by dialysis. Methods used to analyse the micelle to vesicle transitions were transmission electron microscopy and dynamic light scattering. Significant morphological changes occurred upon dilution with TRIS buffered saline and non-buffered saline, and a step-wise transition from the typical cage-like structure via both less well defined ISCOM-like structures and helical micelles to small lipidic particles was observed. Aggregation of the resulting small lipidic particles was noted. The results obtained by dynamic light scattering complemented these findings. With increasing dilution factors, increase in particle size and polydispersity was observed. Zeta-potentials showed a trend towards less negative values upon dilution, indicating that saponins were not retained within the lipid matrix. The results indicated that at least partial separation of Quillaja saponins from the remaining colloidal species occurred upon dilution with aqueous solutions. The release of saponins upon dilution may be an important aspect of how ISCOMs work.