The neuroprotective agent riluzole is used for the symptomatic treatment of motoneuron disease, which strongly affects the brainstem nucleus hypoglossus. The mechanism of action of riluzole was investigated using, as a model, patch-clamp recording from hypoglossal motoneurons of the neonatal rat brainstem slice preparation. In the presence of riluzole (10 microm), theta-rhythm oscillations evoked by nicotine continued even though the persistent inward current (comprising sodium and calcium components) was halved, but they disappeared when the high frequency of spontaneous glutamatergic currents waned. Riluzole fully inhibited the persistent sodium current and partly depressed a tetrodotoxin (TTX)-insensitive slow current antagonized by Mn(2+) or Cd(2+). Repetitive firing was inhibited by riluzole without changing single action potentials. In the presence of TTX, riluzole depressed miniature glutamatergic currents occurring at high rate. Synaptic transmission with low release probability became sensitive to riluzole if release was stimulated by high potassium solution. Miniature current frequency was depressed by the N-methyl-D-aspartic acid (NMDA) receptor antagonist D-amino-phosphonovaleriate (50 microm), which fully occluded the action of riluzole. As riluzole is a protein kinase C (PKC) inhibitor, the PKC antagonist chelerythrine (2.5 microm) mimicked the effect of riluzole and prevented it. In summary, riluzole blocked the persistent sodium current fully, and the calcium one partly, plus it decreased glutamatergic transmission probably via inhibition of PKC that regulated presynaptic NMDA receptors having a facilitatory effect on glutamate release. Controlling NMDA receptor function and, thus, excitatory transmitter release via modulation of PKC suggests a novel potential target to contrast glutamate excitotoxicity in this motor nucleus.
The influence of Pulsed Electric Field (PEF) pretreatment of blueberry fruits (Vaccinium myrtillus L.), both on the extraction yield and antioxidant properties of juice obtained by pressing and on the on the recovery of bioactive compounds from berry by-products (press cake) by extraction with solvent, was investigated. PEF treatments carried out at field strengths of 1, 3, and 5 kV/cm and an energy input of 10 kJ/kg achieved a cell disintegration index (Z p ) of 0.70, 0.80, and 0.87, respectively. Mechanical pressing (1.32 bar for 8 min) of PEF-treated berries (1, 3, and 5 kV/cm at 10 kJ/kg) significantly increased the juice yield (+28 %) compared with the untreated sample. The juice obtained from PEF pre-treated berries also had a significantly higher total phenolic content (+ 43 %), total anthocyanin content (+60 %) and antioxidant activity (+31 %). However, PEF treatment intensity higher than 1 kV/cm did not significantly improve the quantitative or qualitative characteristics of the juice. Compared to the untreated sample, higher amounts of total phenolics (+ 63 %), total athocyanins (+78 %) and antioxidant activity (+ 65 %) were detected in the press cake extracts. PEF treatment of higher intensity resulted in better extractability of bioactive compounds from blueberry press cake. The results obtained from this study demonstrate the potential of PEF as a mild pretreatment method to improve the efficiency of the industrial processing of berry fruits.
In the neonate the muscles of the tongue, which are exclusively innervated by the XII cranial nerves originating from the brainstem nucleus hypoglossus, must contract rhythmically in coincidence with breathing, suckling and swallowing. These motor commands are generated by hypoglossal motoneurons excited by glutamatergic inputs. Because in forebrain areas the efficiency of glutamatergic transmission is modulated by neuronal nicotinic receptors (nAChRs), the role and identity of nAChRs within the nucleus hypoglossus of the neonatal rat were explored using an in vitro brainstem slice preparation. This area expressed immunoreactivity for alpha4, alpha7 and beta2 nAChR subunits. Whole-cell patch-clamp recording from hypoglossal motoneurons showed lack of spontaneous cholinergic events mediated by nAChRs even in the presence of a cholinesterase inhibitor. However, pharmacological antagonism of alpha7- or beta2-containing receptors depressed glutamatergic currents arising either spontaneously or by electrical stimulation of the reticular formation. Hypoglossal motoneurons expressed functional nAChRs with characteristics of alpha4beta2 and alpha7 receptor subunits. Such receptors underwent fast desensitization (time constant of 200 ms) with full recovery within 1 min. Low (0.5 microm) concentration of nicotine first facilitated glutamatergic transmission on motoneurons and later depressed it through receptor desensitization. When 0.1 microm nicotine was used, only depression of synaptic transmission occurred, in keeping with the suggestion that nAChRs can be desensitized without prior activation. These results highlight the role of tonic nAChR activity in shaping excitatory inputs to hypoglossal motoneurons, and suggest that nAChR desensitization by ambient nicotine could contribute to disorders of tongue muscle movements.
Sonoporation is a feasible method to deliver BLM in to several types of human cancer cell lines. Efficiency of cell sonoporation correlated well with MB sonodestruction, providing a possibility to optimize US parameters by measuring MB sonodestruction.
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