Attention and executive functions in a rat model of chronic epilepsy.

OBJECTIVE: Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium-pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored. METHODS: Thirty-five Sprague-Dawley rats were subjected to lithium-pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five-choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus). RESULTS: Lithium-pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage. SIGNIFICANCE: This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium-pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats.

Regulation of medical diagnostics and medical devices in the East African community partner states.

BACKGROUND: Medical devices and in vitro diagnostic tests (IVD) are vital components of health delivery systems but access to these important tools is often limited in Africa. The regulation of health commodities by National Regulatory Authorities is intended to ensure their safety and quality whilst ensuring timely access to beneficial new products. Streamlining and harmonizing regulatory processes may reduce delays and unnecessary expense and improve access to new products. Whereas pharmaceutical products are widely regulated less attention has been placed on the regulation of other health products. A study was undertaken to assess regulation of medical diagnostics and medical devices across Partner States of the East African Community (EAC). METHODS: Data was collected during October 2012 through desk based review of documents and field research, including face to face interviews with the assistance of a structured questionnaire with closed and open ended questions. Key areas addressed were (i) existence and role of National Regulatory Authorities; (ii) policy and legal framework for regulation; (iii) premarket control; (iv) marketing controls; (v) post-marketing control and vigilance; (vi) country capacity for regulation; (vii) country capacity for evaluation studies for IVD and (viii) priorities and capacity building for harmonization in EAC Partner States. RESULTS: Control of medical devices and IVDs in EAC Partner States is largely confined to national disease programmes such as tuberculosis, HIV and malaria. National Regulatory Authorities for pharmaceutical products do not have the capacity to regulate medical devices and in some countries laboratory based organisations are mandated to ensure quality of products used. Some activities to evaluate IVDs are performed in research laboratories but post market surveillance is rare. Training in key areas is considered essential to strengthening regulatory capacity for IVDs and other medical devices. CONCLUSIONS: Regulation of medical devices and in vitro diagnostics has been neglected in EAC Partner States. Regulation is weak across the region, and although the majority of States have a legal mandate to regulate medical devices there is limited capacity to do so. Streamlining regulation in the EAC is seen as a positive aspiration with diagnostic tests considered a priority area for harmonisation.

A comprehensive behavioral evaluation in the lithium-pilocarpine model in rats: effects of carisbamate administration during status epilepticus.

PURPOSE: Administration of carisbamate during status epilepticus (SE) prevents the occurrence of motor seizures in the lithium-pilocarpine model and leads in a subpopulation of rats to spike-and-wave discharges characteristic of absence epilepsy. Widespread neuroprotection accompanied this change in seizure expression. To assess whether these carisbamate-induced changes affected comorbidity, we used a large battery of behavioral tests in rats that had developed temporal lobe or absence-like seizures. METHODS: Lithium-pilocarpine or saline was administered to 60 adult rats. Carisbamate (90 mg/kg) or diazepam and saline was given 1 h after SE onset, and repeated 8 h later and twice daily over 6 more days. Rats were video-monitored for 2 months. Subsequently, locomotor activity, anxiety, and various types of memory were assessed. KEY FINDINGS: In rats with motor seizures, treated or not with carisbamate, all features of behavior were impaired compared to controls. Rats exhibiting absence-like seizures after carisbamate treatment behaved as controls in all paradigms tested along with widespread neuroprotection. SIGNIFICANCE: Carisbamate treatment leading to absence-like instead of temporal lobe seizures impressively prevented behavioral comorbidities reported by patients with epilepsy as the most disabling.