Certain antiepileptic drugs (AEDs) that are commonly used to treat seizures in children also affect cognition, and these effects can persist into adulthood, long after drug withdrawal. Widespread enhancement of apoptosis may be one mechanism underlying these lasting cognitive changes. Whether AEDs affect other processes in brain development during early postnatal life has not, however, been systematically analyzed. Here we determined whether chronic administration of common AEDs during early life alters cell proliferation and neurogenesis in the hippocampus. Postnatal day 7 (P7) rats received phenobarbital, clonazepam, carbamazepine, valproate, topiramate, or vehicle for 28 days. Bromodeoxyuridine was administered on P34 to label dividing cells. Cell proliferation was assessed 24 hr later, and cell survival and differentiation were assessed 28 days later. Phenobarbital and clonazepam significantly inhibited cell proliferation by 63% and 59%, respectively, and doublecortin immunoreactivity (indicator of neurogenesis) in the dorsal hippocampus was also significantly decreased by 26% and 24%, respectively. Survival of new cells steadily decreased in phenobarbital and clonazepam groups over 28 days. Reduced cell proliferation and survival resulted in fewer new neurons in the dentate gyrus, as confirmed by neuronal counting on P62. There were, however, no differences in cell distribution pattern or differentiation toward neuron and glial cells when phenobarbital and clonazepam groups were compared with controls. There were no changes in rats exposed to carbamazepine, valproate, or topiramate. Thus, inhibiting cell proliferation, survival, and neurogenesis in the developing hippocampus may be another potential mechanism underlying brain impairment associated with certain AED therapies in early life.

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The cyclic Arg-Gly-Asp (cRGD) peptides are widely used as tumor-targeting ligands due to their specific binding ability to integrin αvβ3, which is overexpressed on the surface of various cancer cells and the endothelial cells of new blood vessels within tumor tissues. In this paper, the postinsertion strategy of DSPE-PEG2000-cRGD has been applied to the nanoparticles of 3′,3″-bis-peptide-siRNA (pp-siRNA) encapsulated by gemini-like cationic lipid (CLD) and neutral cytosin-1-yl lipid (DNCA) from our lab. It was confirmed that the nanoparticles of pp-siRNA/CLD/DNCA/DSPE-PEG2000-cRGD (PCNR) were able to specifically target tumor cells with highly expressed integrin αvβ3; moreover, it efficiently downregulated the levels of BRAF mRNA and the BRAF protein and inhibited cell proliferation in A375 cells, in comparison with the nontargeted nanocomplex of pp-siRNA/CLD/DNCA/cRAD (PCNA). The uptake pathways of PCNR are mostly dependent on CvME-mediated endocytosis and macropinocytosis in A375 cells, which could bypass lysosome or quickly lead to the lysosomal escape to reduce siRNA degradation. Finally, the biodistribution study showed that PCNR exhibited a high ability to accumulate in tumor tissues. These results suggest that the nanocomplex of PCNR is promising to be highly effective in the treatment of melanomas including their mutation.

In the past decade, most studies on levetiracetam were conducted on patients aged > or = 4 years of age. The authors sought to assess the efficacy and safety of levetiracetam as an adjunctive treatment of children <4 years of age with refractory epilepsy. The mean levetiracetam dosage used on the 24 patients in this study was 38.85 mg/kg per day, and the mean duration of treatment was 40 weeks. During the study, levetiracetam was tapered off in 2 patients due to seizure worsening and was discontinued in other 2 patients due to unacceptable adverse effects. Levetiracetam therapy was effective in 58.3% of patients, with 20.8% achieving seizure freedom. Eight patients showed no obvious response and the remaining 2 patients showed divergent responses. Although adverse effects were seen in 37.5% of patients, all adverse effects were tolerable or resolved with time or discontinuation. Therefore, the authors conclude that levetiracetam treatment is effective and safe in young children with refractory epilepsy.