sec-Butyl-propylacetamide (SPD) and two of its stereoisomers rapidly terminate paraoxon-induced status epilepticus in rats.

OBJECTIVE: Organophosphates (OPs) are commonly used insecticides for agriculture and domestic purposes, but may also serve as nerve agents. Exposure to OPs result in overstimulation of the cholinergic system and lead to status epilepticus (SE), a life-threatening condition that is often resistant to treatment. SE is associated with significant neuronal damage, neurocognitive dysfunction, and the development of lifelong epilepsy. Therefore, rapid termination of SE and prevention of brain damage is of high interest. Here we tested the efficacy of sec-butyl-propylacetamide (SPD) and two of its individual stereoisomers, (2S,3S)-SPD and (2R,3R)-SPD, in discontinuing OP-induced seizures. SPD is a one carbon homolog of valnoctamide, a central nervous system (CNS)-active constitutional isomer of valproic acid (VPA) corresponding amide valpromide. METHODS: Rats were implanted with epidural telemetric electrodes to allow electrocorticography (ECoG) recording 24 h prior, during and 24 h after poisoning with the OP paraoxon (at a dose equivalent to 1.4 LD50 Median lethal dose). All rats were provided with antidotal treatment of atropine and toxogonin. Epileptic activity was measured using a novel automated system to evaluate the different effects of midazolam, SPD, and its individual stereoisomers in comparison to nontreated controls. RESULTS: Treatment with SPD or its individual stereoisomer (2S,3S)-SPD significantly shorten paraoxon-induced SE and reduced the duration of recorded pathologic activity after SE was terminated. (2S,3S)-SPD was superior to racemic-SPD in diminishing delayed pathologic epileptiform activity within the first 8 h after SE. SIGNIFICANCE: These results suggest SPD as an efficient drug for the rapid termination of SE and pathological epileptiform activity following OP poisoning, a strategy to reduce neuronal dysfunction and the risk for lifelong epilepsy.

[Infant botulism].

Infant botulism is a paralytic syndrome which manifests as a result of ingesting spores of the toxin secreting bacterium Clostridium botulinum by infants. As opposed to botulism in adults, treating infant botulism with horse antiserum was not approved due to several safety issues. This restriction has led to the development of Human Botulism Immune Globulin Intravenous (BIG-IV; sells under BabyBIG). In this article we review infant botulism and the advantages of treating it with BIG-IV.

Using Cell Phone Technology to Investigate a Deliberate Bacillus anthracis Release Scenario.

Unusual biological events and outbreaks require rapid epidemiologic investigation and contact tracing procedures, allowing optimal handling of resources. Currently, these are resource intensive, time consuming, and extremely complex, requiring large teams of trained and prepared personnel. The goal of this study was to determine whether a technological alternative to the classic systems, based on the use of mobile phones and a unique algorithm, could perform a complete epidemiologic investigation in a setting of a bioterrorism scenario. The system was tested with 32 volunteers during a bioterrorism simulation drill, with quantitative assessment of key outcome measures: perform a complete analysis of the scenario, determine the fundamental biological attributes of the scenario, distinguish between related and unrelated cases, and identify possible exposed people among a known group of participants. The system fully achieved the objectives in just under 5 hours from the beginning of the simulation with only 3 false-positive "exposed" participants, while identifying all 11 true-positive "exposed" participants (overall accuracy of 85%). We find the system advantageous over currently used tools in a way that could be integrated in conjunction with current outbreak epidemiologic investigation tools and syndromic surveillance efforts to shorten the response time of national authorities in handling adverse biological events.