Selective hyperactivation of JNK2 in an animal model of temporal lobe epilepsy.

c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are derived from three genes, Jnk1-3. These kinases are involved in cellular responses to homeostatic insults, such as inflammation and apoptosis. Furthermore, increased JNK expression and activation are associated with debilitating neurodegenerative diseases, including Alzheimer's and Parkinson's. We previously reported elevated levels of phosphorylated JNK (pJNK), indicative of JNK hyperactivation, in the CA1 hippocampus of chronically epileptic rats. We also showed that pharmacological inhibition of JNK activity reduced seizure frequency in a dose-dependent fashion (Tai TY et al., Neuroscience, 2017). Building on these observations, the objectives of this current study were to investigate the timeline of JNK activation during epileptogenesis, and to identify the JNK isoform(s) that undergo hyperactivation in the chronic epilepsy stage. Western blotting analysis of CA1 hippocampal homogenates showed JNK hyperactivation only during the chronic phase of epilepsy (6-9 weeks post-status epilepticus), and not in earlier stages of epileptogenesis (1 h, 1 day, and 1 week post-status epilepticus). After enrichment for pJNK by immunoprecipitation, we identified JNK2 as the only significantly hyperactivated JNK isoform, with expression of the 54 kDa pJNK2 variant elevated to a greater extent than the 46 kDa pJNK2 variant. Expression of the total amounts of both JNK2 variants (phosphorylated plus non-phosphorylated) was reduced in epilepsy, however, suggesting that activation of upstream phosphorylation pathways was responsible for JNK2 hyperactivation. Since our prior work demonstrated that pharmacological inhibition of JNK activation had an antiepileptic effect, JNK2 hyperactivation is therefore likely a pathological event that promotes seizure occurrences. This investigation provides evidence that JNK2 is selectively hyperactivated in epilepsy and thus may be a novel and selective antiepileptic target.

Modification of microneedles using inkjet printing.

In this study, biodegradable acid anhydride copolymer microneedles containing quantum dots were fabricated by means of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing. Nanoindentation was performed to obtain the hardness and the Young's modulus of the biodegradable acid anhydride copolymer. Imaging of quantum dots within porcine skin was accomplished by means of multiphoton microscopy. Our results suggest that the combination of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing enables fabrication of solid biodegradable microneedles with a wide range of geometries as well as a wide range of pharmacologic agent compositions.

Adolescent chemical dependency treatment in an HMO.

HMOs are under increasing pressure to expand benefits and services for treatment of adolescents who abuse alcohol and drugs. Little information exists, however, on these programs. This article describes a comprehensive adolescent chemical dependency treatment program within an HMO and presents data on use, costs, and results. Characteristics of clients were similar to adolescents seen in community treatment programs. Less than 1% of the HMO adolescent population sought treatment, and the mean number of outpatient treatment visits was 9.7. The median was between two and three visits, and the mode was one visit. Thirty-four percent of the adolescents required residential treatment, and 65% of the adolescents completed the recommended 28-day stay. The additional premium cost per member per month for adolescent chemical dependency treatment was approximately $0.28. A telephone follow-up survey of a random sample of treated adolescents found that most adolescents had reduced their use of alcohol and drugs and had made improvements in other areas of their lives. Few adolescents, however, met the program's goal of total abstinence.