Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), undetectable in resting neural tissue, accumulates in brain during seizures. A hetrazepine, BN-50730, is shown here to displace [3H]PAF-specific binding from microsomal, but not from synaptosomal membranes, indicating selectivity for a high affinity intracellular binding site. Rats pretreated with BN-50730 by intraperitoneal or intracerebroventricular injection exhibited an inhibition of the electroconvulsive shock (ECS)-induced expression of c-fos and zif-268 in hippocampus. A much more pronounced, dose-dependent inhibition of ECS-induced zif-268 mRNA in hippocampus by intracerebroventricular injection of BN-50730 was observed. It is concluded that, in the hippocampus, PAF is a mediator of the expression of zif-268 and, to a lesser extent, c-fos through an intracellular specific binding site. Thus, PAF may be a messenger in signal regulated zinc-finger transcription factors, and in other immediate-early genes involved in long-term synaptic plasticity changes.
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PMID:Platelet-activating factor is a messenger in the electroconvulsive shock-induced transcriptional activation of c-fos and zif-268 in hippocampus. 814 3

The administration of reagents selectively responding to zinc to dogs, cats, rabbits, golden hamsters and mice induced epileptoid seizures. The convulsive action of these agents was due to zinc binding in the hippocampus.
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PMID:[Epileptiform seizures induced by reagents selective for zinc]. 818 13

Human epileptics have been reported to have low blood manganese (Mn) concentrations in comparison to nonepileptics, an observation that is important because Mn deficiency can increase seizure susceptibility in experimental animals. Factors that have been suggested to contribute to the low blood Mn levels in epileptics include anticonvulsant use, seizure-induced tissue redistribution of Mn, and genetics; in the present study, the first of these possibilities was tested. Wistar rats were fed semipurified diets containing diphenylhydantoin ([DPH] 3 g/kg diet), phenobarbital ([PB] 2 g/kg diet), or primidone ([PRIM] 3 g/kg diet) for 7 weeks, at which time they were killed and tissues collected and analyzed for Mn, zinc (Zn), copper (Cu), and iron (Fe) concentrations. In comparison to pair-fed rats, DPH- and PRIM-fed rats had significantly elevated liver Mn concentrations, while Mn concentrations in blood, brain, heart, and kidney were unaffected by anticonvulsant exposure. Changes in the concentrations of Zn, Cu, and Fe in specific tissues were also found. Overall, these findings suggest that the anticonvulsants tested do not lead to significant derangements in the metabolism of Mn.
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PMID:Anticonvulsant-induced changes in tissue manganese, zinc, copper, and iron concentrations in Wistar rats. 834 1

The ability of diethyldithiocarbamate (DEDTC) to prolong electrical afterdischarge (AD) and lower the threshold for behavioral seizures elicited by stimulation of the perforant path (PPS) was examined. DEDTC was given in doses of 25, 50, and 100 mg/kg, IP. The effects of DEDTC on the threshold for wet dog shakes (WDS) and the number of WDS elicited by PPS were inconsistent. It had no effect on the duration of AD accompanied with WDS. However, DEDTC, at both 50 and 100 mg/kg, significantly lowered the threshold for rearing accompanied with forelimb clonus. At 100 mg/kg, it also prolonged the duration of AD occurring with these seizures. The effects of DEDTC were transitory and coincided with the time course for its ability to chelate the mossy fiber intravesicular pool of zinc (i.e., that which is released by activation of dentate granule cells). It is suggested that release of zinc from the mossy fibers may serve to protect the hippocampus from paroxysmal seizure activity.
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PMID:Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path. 839 31

Certain features of Wilson's disease (WD) in Asia have been found to be different from those in other continents. The higher prevalence rate in Japan is presumably due to a higher consanguinity rate. In Chinese there is a tight linkage between WD and two gene loci for esterase D and retinoblastoma in the long arm of chromosome 13. The high proportion of patients with hepatic presentation accounts for early onset of WD in the Japanese and Chinese series. Skeletal involvement, leg hyperpigmentation, dark complexion, amenorrhea, epileptic seizures, and cerebral white matter degeneration are relatively more common among WD patients in Asia. Excessive copper in the liver appears to have a protective effect against hepatocellular carcinoma and type B hepatitis. Electrophysiological studies suggest widespread functional disturbances of the CNS in WD. Side-effects from penicillamine are rather frequent and often lead to interruption of the therapy. Trien is found to be effective without adverse reactions. Oral zinc therapy may be a suitable alternative for long-term management of WD patients in developing Asian countries.
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PMID:Geographic variations in Wilson's disease. 841 43

A Bull Terrier that was continuously chasing its tail was examined clinically, electroencephalographically, and by computed tomography of the head. The dog was also given test treatments with an anticonvulsant (diazepam) and a pure opioid antagonist (naloxone). The dog appeared to be hysterical and dissociated from its surroundings. Electroencephalography revealed a seizure pattern that was most marked over the temporal lobe, and computed tomography revealed mild hydrocephalus. Diazepam effectively controlled tail chasing, whereas naloxone did not. The dog was discharged on anticonvulsant therapy but subsequently had to be euthanatized when aggression developed. Results of examination and treatment have led the investigators to propose a hereditary mechanism for tail chasing, perhaps related to zinc malabsorption.
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PMID:Tail chasing in a bull terrier. 845 9

In the kindling model of temporal lobe epilepsy, several physiological indicators of inhibition by gamma-aminobutyric acid (GABA) in the hippocampal dentate gyrus are consistent with an augmented, rather than a diminished, inhibition. In brain slices obtained from epileptic (kindled) rats, the excitatory drive onto inhibitory interneurons was increased and was paralleled by a reduction in the presynaptic autoinhibition of GABA release. This augmented inhibition was sensitive to zinc most likely after a molecular reorganization of GABAA receptor subunits. Consequently, during seizures, inhibition by GABA may be diminished by the zinc released from aberrantly sprouted mossy fiber terminals of granule cells, which are found in many experimental models of epilepsy and in human temporal lobe epilepsy.
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PMID:Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model. 855 76

Early diagnosis and appropriate treatment of biochemical abnormalities accompanying neonatal seizures is important for effective seizure control and to avoid further brain damage. The present study was carried out on 35 neonates to determine the frequency of various biochemical abnormalities in neonatal seizures. Diagnostic evaluation included estimation of levels of serum calcium, phosphorus, magnesium, sodium, potassium, zinc, and blood glucose. Two-thirds of the neonates with seizures had biochemical disturbances in their sera. A variety of abnormalities occurred in asphyxiated infants, including hyponatremia, hypoglycemia, hypocalcemia, and hypomagnesemia. Primary metabolic disorders accounted for one-forth of the cases of neonatal seizures, the most common being hypoglycemia, hypoglycemia/hypocalcemia, and hypocalcemia/hyperphosphatemia. Inappropriate intrauterine growth, inadequate feeding, and feeding with cow's milk were the main risk factors for primary metabolic seizures. Hyponatremia was a frequent finding in seizures resulting from brain damage like birth asphyxia, meningitis, and intracranial hemorrhage. No infant had hypernatremia, hyperkalemia, hypokalemia, or low serum zinc.
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PMID:Biochemical abnormalities in neonatal seizures. 863 5

Excitatory amino acids (EAA) became known as neurotransmitters of the central nervous system (CNS) in the last decade. The most studied EAA are glutamate and aspartate. Both are synthetized by the same mechanism as gamaaminobutyric acid. (Fig. 1). Glutamate is widely distributed in the CNS and the spinal cord, being the areas of higher concentration the cerebral cortex, the hypocampus and the cerebellum. There have been identified two type of receptors for glutamate: ionotropic and metabotropic. The former includes three different types: NMDA, AMPA and KA. NMDA receptor is coupled to a Na+ and Ca2+ channel being the second ion the most important one. This receptor has several sites of binding for various substances. Along with the site for N-methyl-D-aspartate, which binds glutamate and/or aspartate, there have been identified a site for the binding of glycine (which is different from the strychnine sensitive one), a site for poliamines such as spermine and spermidine, and a site for the binding of Zn2+ (Table 1). AMPA receptor is associated to a Ca(2+)-Na+ channel, being in this case the Na+ the most important ion. There are two metabotropic type receptors: L-AP4 and trans-ACPD. Both are coupled to a G protein and agonists exert their action increasing phospholipase C activity which in turn induces an increment of IP3 and diacyl-glicerol, and a consecutive releasing of Ca2+ from intracellular stores. EAA play a role in some physiological processes. One of them is long-term potentiation (LTP), an electrochemical phenomenon involved in memory consolidation. Antagonists of NMDA and AMPA receptor prevent the development of LTP, and conversely, the agonist of glycine site of NMDA receptor--D-cycloserine--facilitates memory consolidation. Since 1957, EAA are considered neurotoxic substances and there are many indirect evidences to support this statement. Pathogenesis of neuronal damage elicited by EAA involves the events shown in Fig. 3. Prevention of the cascade of events that provokes neurotoxicity may be achieved by NMDA antagonists, but once it has begun it may be only aborted subtracting the Ca2+ from the medium, using nifedipine or blocking AMPA receptor with an antagonist (CNQX). EAA have been shown to play a toxic role in neuronal damage induced by ischemia. Research using various experimental models demonstrated that NMDA receptor antagonists (i.e. MK 801) blocks postischemic damage. Interventions at various levels of the pathogenic cascade shown in Fig. 4 provoke the same results. There is enough evidence to suspect that NMDA and AMPA receptors are altered in epilepsy. NMDA antagonists (i.e. MK801 or AP5) prevent the development of epileptic seizures induced by kindling; CNQX, an AMPA antagonist, blocks the increase in electrical activity induced by K+ in slices of hypocampus; felbamate, an antiepileptic drug, blocks the glycine site (not strychnine sensitive) decreasing NMDA receptor activity. Several neurodegenerative disorders have been associated with exogenous administration or accidental intake of EAA. (i.e. neurolatirism, Guam disease). Similarities between these diseases and lateral aminotrophic sclerosis indicate that in the latter EAA may play a pathogenic role. Finally, the psychotomimetic effect of phencyclidine (an antagonist of NMDA receptor) suggests that in schizophrenia, together with dopaminergic neurotransmission impairment, some dysfunction of glutamate pathways may be present.
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PMID:[Role of excitatory amino acids in neuropathology]. 872 78

The mechanisms underlying febrile convulsions (FC), which have multiple etiological factors, are not yet clear. The aim of the present study was to determine whether there were any changes in serum and cerebrospinal fluid (CSF) zinc (Zn) levels in children with febrile convulsion during seizures. A total of 102 children were included in the study, with four groups formed as follows: group A, 40 children with FC (aged 9 months to 5 years); group B. 20 children having fever without convulsion (aged 6 months to 5 years); group C, 20 children with afebrile convulsion (aged 6 months to 6 years) and group D, 22 healthy children (aged 5 months to 6 years). Serum and CSF zinc levels for groups A, B and C and serum Zn levels only for group D were measured. The serum Zn levels of 17 children in group A were again measured during healthy periods. Serum Zn levels of groups A, B, C and D had a mean of 0.70 +/- 0.10 mg/dL, 1.07 +/- 0.08 mg/dL. 1.26 +/- 0.32 mg/dL and 1.17 +/- 0.21 mg/dL, respectively, and the values of group A were lower than those of the other three groups (P < 0.001). In group B, serum Zn levels were also lower than those of groups C and D (P < 0.05). The CSF Zn levels of groups A, B and C were found to have a mean of 0.07 +/- 0.02 mg/L, 0.12 +/- 0.02 mg/L and 0.14 +/- 0.04 mg/L, respectively. In group A, the CSF Zn levels were lower than those of groups B and C (P < 0.001), and in group B they were lower than those of group C (P < 0.05). For the 17 patients in group A, serum Zn levels during healthy periods (0.87 +/- 0.10 mg/dL) were found to be higher than the values shortly after seizures, but lower than those of groups B, C and D (P < 0.001). We could not observe any relationship between zinc levels of the serum and CSF and the degree and duration of the fever. These findings suggest that serum and CSF Zn levels decreased during infectious diseases, and that this decrease was more significant in patients with FC.
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PMID:Serum and cerebrospinal fluid zinc levels in children with febrile convulsions. 874 13


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