Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat.
ABSTRACT This study was conducted to characterize the post-pubertal developmental aspects on seizure susceptibility and severity as well as calcium/calmodulin protein kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to ninety-day-old rats, in 10-day increments, were studied. This corresponds to a developmental age group that has not received thorough attention. The pilocarpine model of SE was characterized both behaviorally and electrographically. Seven criteria were analyzed for electrographical characterization: seizure severity, SE susceptibility, the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death. After 1 h of SE, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. There was no developmental effect on the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death; however, there was a significant effect on SE probability and seizure severity. Once SE was expressed, all animals showed a decrease in both cortical and hippocampal CaM kinase II activities. Conversely, seizure activity in the absence of SE did not result in a decrease in CaM kinase II activity. The data suggest that there is a gradual age-dependent modulation of SE susceptibility and seizure severity within the developmental stages studied. Additionally, once status epilepticus is observed at any age, there is a corresponding SE-induced inhibition of CaM kinase II.
SourceAvailable from: Alessandro Ceschi[Show abstract] [Hide abstract]
ABSTRACT: Context. Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. Methods. A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. Results. We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4–50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8–29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3–19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5–17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4–14.0%). In adolescents (15–19y/o) 23.9% (95% CI: 17.6–31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3–9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8–35.2%) and 10.9% (95% CI: 7.1–16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. Conclusions. Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults.Clinical Toxicology 05/2014; DOI:10.3109/15563650.2014.918627 · 3.12 Impact Factor
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ABSTRACT: Within 5years, the United States will join the rest of the world’s industrialized countries and many emerging economies in adopting International Financial Reporting Standards (IFRS). However, many educational programs have not yet developed full curricula or integrated case studies in existing programs to compare and contrast how US GAAP and IFRS would record and present major accounting transactions.Based on events that reflect real world scenarios, this study presents a series of three Raleigh Building Products cases as an instrument to fill the current IFRS education void. The first case in the series discusses US GAAP acquisition and consolidation activities, the second case examines asset and intangible impairment under US GAAP and IFRS, and the last case adds components that differ significantly between US GAAP and IFRS. The series of cases can be used stand alone or build upon each other throughout the semester. The combined cases focus on the following key concepts: (1) calculating acquisition price; (2) preparing combination financial statements including deleting LIFO reserves; (3) measuring goodwill and other intangibles; (4) determining the impairment of goodwill due to economic declines; and (5) comparing fundamental differences between US GAAP to IFRS. The attached teaching notes detail these matters and discuss the statements of cash flows under US GAAP and IFRS.Results from classroom use indicate that this case will benefit accounting students and practitioners as IFRSs become effective in the US.Journal of Accounting Education 06/2010; 28(2):128-137. DOI:10.1016/j.jaccedu.2011.03.003