[Interactions between anti-seizure medications and recommendations for combination treatment]. / Interaktionen zwischen anfallssupprimierenden Medikamenten und Empfehlungen für Kombinationstherapien.

Pharmacotherapy is the most important pillar in the treatment of epilepsies. In approximately 50% of epilepsy patients monotherapy with anti-seizure medications (ASM) is insufficient. The knowledge of specific drug interactions in combination therapies is essential to recognize and avoid adverse side effects up to relevant therapy risks, including loss of efficiency and intoxication. Interactions can be of a pharmacokinetic or pharmacodynamic nature. Some effects of interactions in combination therapies can also be advantageous. Therapeutic drug monitoring in serum is not necessary for all ASMs and should be used rationally: however, it should be performed consistently if the indications are present. This review article provides fundamental knowledge about the most relevant interactions between ASMs and the indications for therapeutic drug monitoring.

Assessment of pelvic injuries treated with ilio-sacral screws: injury severity and accuracy of screw positioning.

PURPOSE: The aim of this study was to analyse possible indicative parameters for percutaneous ilio-sacral stabilisation and to identify parameters associated with screw misplacement. METHODS: Cohort study, level I trauma centre. INCLUSION CRITERIA: (1) unstable pelvic injury, (2) percutaneous ilio-sacral screws placement. EXCLUSION CRITERIA: (1) sacral dysmorphy, (2) failed closed reduction, (3) navigated techniques. Indicative parameters were age, gender, body mass index, number of screws, screw angulation, fracture type and injury severity. End points were ilio-sacral screw position and associated complications. Screw placement accuracy was graded as follows: grade 0, no perforation; grade 1, perforation <2 mm; grade 2, perforation from 2 to 4 mm; grade 3, ≥4 mm perforation. RESULTS: Between March 2008 and March 2013, 102 (53 women) patients were included (mean age, 48.5 ± 21.4 years). The Injury Severity Score (ISS) and New Injury Severity Score (NISS) were 18.9 ± 9.9 and 22.3 ± 22.3, respectively. The positions of 137 ilio-sacral screws were analysed. Of all screws, 87.6 % (120) were placed satisfactory (<2 mm perforation). The incidence of screw misplacement was significantly higher in the case of two unilateral S1 screws compared with a single screw (failure rate: two unilateral screws 23.1 % vs single screw 7.0 %; p < 0.05). Screw perforation anterior to the lateral mass (in-out-in) represented the most frequent malposition. Revision was necessary in three cases due to malpositioning. Furthermore, no major complication occurred. CONCLUSIONS: We conclude, that twofold ilio-sacral screw positioning from one side increases the risk for screw misplacement. In this case, alternative techniques like navigation should be considered. Anterior screw perforation represents a common problem with a high incidence and warrants particular attention.

The brain selenoproteome: priorities in the hierarchy and different levels of selenium homeostasis in the brain of selenium-deficient rats.

The application of radionuclides for the localization of essential trace elements in vivo and the characterization of their binding proteins is a story of intermittently made improvements of the techniques used for their detection. In this study we present the use of neutron activation analysis and different autoradiographic imaging methods including real-time digital autoradiography to reveal new insights in the hierarchy of selenium homeostasis. Selenoproteins containing the essential trace element selenium play important roles in the CNS. Although the CNS does not show the highest selenium concentration in the case of selenium-sufficient supply in comparison with other organs, it shows a high priority for selenium uptake and retention in the case of dietary selenium deficiency. To characterize the hierarchy of selenium supply in the brain, in vivo radiotracer labeling with (75)Se in rats with different selenium status was combined with autoradiographic detection of (75)Se in brain tissue sections and (75)Se-labeled selenoproteins after protein separation by two-dimensional gel electrophoresis. This study demonstrates significant differences in the uptake of (75)Se into the brain of rats with different selenium status. A brain region-specific uptake pattern of the radiotracer (75)Se in selenium-deficient rats could be revealed and the CSF was identified as a key part of the brain selenium homeostasis.

Biochemical analysis of selenoprotein expression in brain cell lines and in distinct brain regions.

Selenium is present in various biologically important selenoproteins. The preferential incorporation of selenium into the brain indicates its significance for this organ, but so far knowledge concerning the cerebral selenoproteome is scarce. We therefore investigated the expression of selenoproteins in various regions of the rat brain, various subcellular fractions and several brain cell lines by (75)Se-labelling, gel electrophoretic separation and autoradiography, with the (75)Se tracer as the selenoprotein marker. Quantitative evaluation of the labelled proteins in selenium-deficient rats revealed information regarding preferentially supplied selenoproteins and their distribution; 21 selenoproteins could be distinguished, among them a novel or modified 15-kDa selenoprotein enriched in the cerebellum cytosol. The selenoproteins differed in the degree of their expression among the brain regions and within a region among the subcellular fractions. Some cell-type-specific selenium-containing proteins were found in the cell lines. Differences in the distribution patterns between mono-cultured and co-cultured endothelial cells and astrocytes showed that mediators produced by other cells could affect the selenoprotein expression of a specific cell-type. This effect might play a role in the uptake and distribution of selenium in the brain but could also be of significance in the selenium metabolism of other tissues.

Susac syndrome with frontal intermittent rhythmic delta activity (FIRDA).

BACKGROUND: Susac syndrome is a rare condition involving the brain, retina, and cochlea. Electroencephalogram (EEG) findings from published case reports show mainly generalized slowing. CASE REPORT: A 30-year-old man presented with acute onset of superior vision loss, unsteady gait, and hearing loss. This was accompanied by short-term memory loss and behavioral and mood changes. MRI showed multiple white matter hyperintensities. The EEG showed frontal intermittent rhythmic delta activity. A diagnosis of Susac syndrome was made and treatment with methylprednisolone, ASA, and Nimodipine was instituted. At one-year follow-up, bilateral hearing loss, mild visual impairment, and mood changes were still apparent. CONCLUSIONS: Frontal intermittent rhythmic delta activity can be seen in Susac syndrome.

Distribution of an 18 kDa-selenoprotein in several tissues of the rat.

By combining methods for trace element analysis, tracer techniques and various biochemical and electrophoretical procedures, information on the characteristics of an 18 kDa-selenoprotein was obtained. By labeling of rats in vivo with [75Se]-selenite and gel electrophoretic separation of the proteins in tissues and subcellular fractions, a larger number of selenium-containing proteins could be distinguished. In most of the tissues investigated a labeled 18 kDa-band was present. After co-electrophoresis of the 18 kDa-bands from kidney, liver and brain we found that they all migrated in the same way. Using ultracentrifugational fractionation the 18 kDa-band was localized in the mitochondrial and microsomal membranes. Two-dimensional electrophoresis showed that it consists of a single selenium-containing protein with an isoelectric point of about 4.9-5.0. By means of proteolytic cleavage of the 18 kDa-protein and separation of its peptides by tricine-SDS-PAGE six selenium-containing peptides with molecular masses of 17, 16, 14, 12, 10, and 8 kDa were detected. After electrophoretic separation of the mitochondrial and/or microsomal proteins and acid hydrolysis of the electroeluted protein its amino acid composition was analyzed by RP-HPLC. In this way it was shown that selenium is present in the 18 kDa-protein in form of selenocysteine which is a characteristic of a genetically encoded selenoprotein.