Antiepileptic effects of inhibitors of nitric oxide synthase examined in pentylenetetrazol-induced seizures in rats

The effects of intraperitoneal and methyl ester, specific inhibitors of nitric oxide (NO) synthase, were examined on the pentylenetetrazol (PTZ)-induced seizures in rats. The incidence and latency for the onset of myoclonic jerks, clonic seizures, and tonic generalized extension were observed as specific parameters among PTZ-induced seizures. Both drugs preferentially suppressed the tonic generalized extension and prolonged the latency for the onset of each parameter, suggesting NO has a significant effect on the PTZ-induced seizure.     

Seizure Disorders: The Changes With Age

Summary: Age has a profound influence on our approach to the convulsive disorders. Age is a variable which is an important determinant for risk factors for epilepsy. Age, as a surrogate of brain maturation, is a determinant of the specific characteristics of the seizure disorder in those with epilepsy, and age-related changes in these manifestations can be identified. Age is a determinant for the occurrence of acute symptomatic seizures in several types of metabolic or central nervous system insults. Age is a determinant for prognosis, whether one considers remission, medication withdrawal in those entering remission, relapse following prolonged remission, or mortality. Last, age per se seems to be a risk factor for epilepsy independent of other factors. This seems particularly true for partial seizures.     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect.
Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals.
Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min.
Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.     

哺乳妇女单次注射迪波盖司通~长效避孕针后血清和乳液中MPA浓度变化

目的:探讨中国妇女哺乳期使用迪波盖司通后血清和乳液醋酸甲羟孕酮(MPA)浓度变化。方法:10名产后哺乳妇女单次注射迪波盖司通(含MPA150mg),在注射后的第1、2、4、6、8、10和12周采集血样和乳液样本,用放射免疫方法测定MPA。结果:血清MPA浓度于注射后第1周最高,到第2、4周时下降明显,第4周后浓度下降趋势逐渐缓慢。乳液MPA浓度在第1周为最高,第2周比第1周降低了约1/2,之后10周平均浓度变化波动在5.09-8.15ng/ml之间。观察期间乳液/血清MPA浓度比值和曲线下浓度面积比值均为0.55。对象之间和同一对象不同时间点乳液/血清MPA浓度存在明显个体差异。结论:哺乳期使用迪波盖司通,将导致血液和乳液中含有一定量的MPA。     

Postictal Language Dysfunction in Patients with Right or Bilateral Hemispheric Language Localization

Summary: Purpose : As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non-left (right hemisphere or mixed) language dominance.
Methods : Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) >90% seizure reduction after anterior temporal lobectomy with 2-year minimum follow- follow- up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex.
Results : Two hundred twenty-four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non-left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%).
Conclusions : Postictal language testing accurately identifies patients with non-left language dominance and may be useful in selecting appropriate patients for IAT.     

Natural killer cell activity and serum immunoglobulins in epileptic patients

Serum immunoglobulins and the activity of natural killer (NK) cells of 50 epileptic patients (eight with idiopathic generalized epilepsy and 42 with cryptogenic partial epilepsy) and 28 controls have been studied. The values of IgA, IgG and IgM were the same-in patients and controls. The NK activity in controls was linearly related to the effector-to-target ratio, but this linear relationship was not observed in epileptic patients. The cytotoxic activity of NK cells at the lowest effector-to-target ratio was significantly greater in patients than in controls. This increase was observed in each therapy group. Our results seem to confirm a disturbance of the immune system in epileptic patients and suggest that this modification of cellular immunity is not a drug effect but is related to the illness itself.     

Temporal Lobe Epileptogenesis and Epilepsy in the Developing Brain: Bridging the Gap Between the Laboratory and the Clinic. Progression, But in What Direction?

Summary:  The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are still not well understood. Hippocampal sclerosis and temporal lobe epileptogenesis involve a series of pathologies including hippocampal neuronal loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis. However, the causality of these events is unclear as well as their relation to the factors that may precipitate epileptogenesis. Significant differences between temporal lobe epileptogenesis in the adult and immature brain may require differential approaches. Hereditary factors also may participate in some cases of hippocampal sclerosis. The key point is to identify the significance of these age-dependent changes and to design preventive treatments. Novel strategies for the prevention and treatment of mesial temporal lobe epilepsy and hippocampal sclerosis may include rational use of neuroprotective agents, hormonotherapy, immunizations, and immunotherapy.     

Neurocysticercosis in Persons with Epilepsy in Medellín,Colombia

Summary: Purpose: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellin, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. Methods: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. Results: Prevalence of neurocys@ercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellin. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. Conclusions: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.     

Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.