Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Domoic acid (DA), the cause of Amnesic Shellfish Poisoning, is a naturally occurring marine biotoxin that is usually produced by the microscopic algae Pseudo-nitzschia. As is the case for other types of toxic algae, Pseudo-nitzschia outbreaks are becoming more frequent. Acute high-dose symptomology in humans includes vomiting, cramping, coma and death as well as neurological effects such as hallucinations, confusion and memory loss. Experimental studies and medical reports have collectively shown that DA exposure primarily affects the hippocampal regions of the brain and is associated with seizures and the disruption of cognitive processes. The neurobehavioral signature of DA is unique in that it includes transient and permanent changes in memory function that resemble human antegrade amnesia. Experimental studies with adult nonhuman primates have established that DA is a dose-dependent emetic that produces clinical and neuropathological changes consistent with excitotoxicity. Behavioral evaluations of treated rodents have shown that hyperactivity and stereotypical scratching are the first functional markers of toxicity. Mid-dose treatment is associated with memory impairment and behavioral hyperreactivity, suggesting changes in arousal and/or emotionality. At higher doses, DA treatment results in frank neurotoxicity that is characterized by seizures, status epilepticus and death in treated animals. The route of DA exposure is important and influences the severity of effects; intraperitoneal and intravenous treatments produce classic signs of poisoning at significantly lower doses than oral exposure. While developmental studies are few, DA readily crosses the placenta and enters the fetal brain. Domoic acid is not associated with congenital dysmorphia but is linked to persistent changes in motor behavior and cognition in exposed offspring. Comparative research suggests that functional losses associated with DA can be persistent and injuries to the CNS can be progressive. Long-term studies will be necessary to accurately track the expression of DA-related injury, in health and behavior, over the lifespan.
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PMID:Domoic acid: neurobehavioral consequences of exposure to a prevalent marine biotoxin. 1979 96

Domoic acid (DA), a naturally occurring environmental toxin, has been observed to induce status epilepticus in humans, sea lions and pelicans. In a recent Sprague Dawley rat model, domoic acid dosing induced a state of status epilepticus which, after a symptom-free latent period without further dosing, progressed to recurrent spontaneous seizures, a hallmark of epilepsy. Certain individuals in this study also developed unusual behavioral changes, in particular an atypical aggression towards conspecifics. In this report we characterized the progression of aggressive behaviors after DA-induced status epilepticus and explored the relationship between aggressive behavior and recurrent spontaneous seizures. Experimental studies in this laboratory rat model are particularly relevant to California sea lions (Zapholus californianus), which show a spectrum of both epileptic and unusual behaviors, including aggression towards conspecifics in rehabilitation facilities, weeks to months after suspected exposure to domoic acid in the wild.
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PMID:Domoic acid induced status epilepticus promotes aggressive behavior in rats. 2187 11

Domoic acid (DA) causes neurological effects in multiple species upon exposure, including status epilepticus in pregnant sea lions and an epileptic disease state that commonly develops in juveniles. This study aims to define brain toxicokinetic parameters in the pregnant rat in the larger context of maternal-fetal toxin transfer. Specifically, Sprague-Dawley rats were exposed to a low observable effect level of 1.0 mg DA/kg intravenously at gestational day 20, and plasma, brain, and cerebrospinal fluid (CSF) samples were taken at discrete time points over 24 h. Domoic acid concentrations were determined by a tandem LC/MS method recently optimized for brain tissue and CSF. Data showed that 6.6% of plasma DA reached the brain, 5.3% reached the CSF, and DA levels were nearly identical in both brain and CSF for 12 h, remaining above the threshold to activate isolated hippocampal neurons for 2 h. The calculated terminal half-life of CSF was 4 h, consistent with the time for complete CSF regeneration, suggesting that CSF acts as a mechanism to clear DA from the brain.
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PMID:Elimination kinetics of domoic acid from the brain and cerebrospinal fluid of the pregnant rat. 2313 53

Domoic acid toxicosis (DAT) in California sea lions (Zalophus californianus) is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05). Interestingly, 11 apolipoprotein E (ApoE) charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value) and high specificity (92.3% with 85.7% positive predictive value). These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers.
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PMID:Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus) Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis. 2591 66