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)

The neurotransmitter norepinephrine (NE) has been implicated in both the normal expression of long-term neuronal plasticity and in development of epileptiform bursting. Our studies have focused on the modulatory role of NE in a number of epilepsy models, both acute and chronic. Acutely, reduction of extracellular Mg2+ concentration in in vitro brain slices induced spontaneous and evoked epileptiform activity in both the entorhinal cortex (EC) and dentate gyrus (DG), due largely to removal of the voltage-dependent Mg2+ blockade of N-methyl-D-aspartate receptors. Spontaneous ictal events are most prominent in the EC, suggesting an importance of this area in seizure generation. NE was found to exhibit differential modulation of epileptiform activity in the EC and DG. In the EC, NE, acting via alpha 1-receptors, completely blocked low Mg(2+)-induced epileptiform activity. In contrast, in the DG, NE exhibited a beta-receptor mediated prolongation of the low Mg(2+)-induced ictal events, and enhanced the stimulus-induced ionic and field potential changes. These complementary modulatory actions in the EC and DG, may serve to enhance signal transmission through the DG, while simultaneously reducing EC input noise and exerting a potent antiepileptic action in the EC. Chronically, actions of NE in the DG were examined before and after kindling-induced epilepsy, neuronal plasticity produced by daily high-frequency stimulation. NE, acting on beta 1-receptors, depolarized granule cells, increased input resistance, firing and influx of Ca2+ in response to repetitive stimulation, and elicited long-lasting potentiation of synaptic potentials. In addition, NE acting via alpha 1-receptors, attenuated Ca(2+)-dependent regenerative potentials. After kindling-induced plasticity, there were marked reductions in all these effects of NE on granule cells, changes likely to influence kindling-induced seizures, protecting against further enhancement of excitability once plasticity is in place.
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PMID:Noradrenergic modulation of epileptiform bursting and synaptic plasticity in the dentate gyrus. 133 59

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.
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PMID:Combination treatment of high-dose pyridoxal phosphate and low-dose ACTH in children with West syndrome and related disorders. 170 36

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.
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PMID:Computerized analysis of EEG background activity in epileptic patients. 174 59

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting beta 1-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized study, involving four match-pair trials (placebo versus esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures, 160). We administered a 4-min infusion of either placebo or esmolol at the rate of 500 micrograms.kg-1.min-1. We then induced anesthesia with methohexital and succinylcholine. After administration of electrical stimulation for ECT, the rate of infusion decreased to 300 micrograms.kg-1.min-1 for three additional minutes and was then discontinued. Statistically significant reductions in mean heart rate from minute 2 until minute 15 and in maximum heart rate (the mean of each patient's maximum heart rate after seizure changed from 152 +/- 23 to 115 +/- 24 beats/min) occurred in patients given esmolol. During and immediately after infusion, arterial blood pressure also decreased. Finally, the length of seizures decreased, as manifested clinically from 48 +/- 18 to 39 +/- 14 s and on electroencephalogram from 86 +/- 41 to 67 +/- 28 s. We conclude that esmolol effectively controls the hyperdynamic response to ECT and reduces the length of seizures. The significance of the latter to the overall effectiveness of ECT is not known.
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PMID:Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy. 197 95

EEG background activity influenced by antiepileptic drugs (AED) was studied in 109 monotherapy and drug-free epileptic patients using t-Statistical Significance Probability Mappings (t-SPMs). Patients taking phenobarbital (PB) had an increase in alpha 1 and a decrease in alpha 2 activity in comparison with drug-free epileptics. Patients taking PB for generalized seizures with tonic-clonic convulsion only (GTC) also had a significant increase in alpha 1 and a decrease in alpha 2, whereas those with partial seizures (PS) had an increase in theta and beta 1 and a decrease in alpha 2 activity. Patients taking valproic acid (VPA) had a decrease in only beta 1 activity. Patients taking VPA for GTC showed an increase in delta activity, but those with PS did not show any changes. Patients taking carbamazepine (CBZ) for PS exhibited marked slowing with an increase in theta and alpha 1 and a decrease in alpha 2 activity. These results mean that changes in EEG due to AEDs differ depending on the type of seizures. More interestingly, discrepancy between EEG background activity and effects of AEDs was found: In PS type of seizures, the most effective CBZ exhibited striking slowing, PB was next, and VPA was last. In GTC, VPA resulted in greater slowing than PB.
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PMID:[Computerized analysis of EEG background activity in mono-therapeutic patients with epilepsy--relationships between antiepileptic drugs and types of seizures]. 224 78

Actions of norepinephrine (NE) in the dentate gyrus were examined before and after kindling-induced epilepsy, neuronal plasticity produced by daily high-frequency stimulation. NE, acting on beta 1-receptors, depolarized granule cells, increased input resistance, firing and influx of Ca2+ in response to repetitive stimulation, and elicited long-lasting potentiation of synaptic potentials. In addition, NE acting via alpha 1-receptors, attenuated Ca2+-dependent regenerative potentials. After kindling-induced plasticity, there were marked reductions in all these effects of NE on granule cells, changes likely to influence kindling-induced seizures, protecting against further enhancement of excitability once plasticity is in place.
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PMID:Down-regulation of norepinephrine sensitivity after induction of long-term neuronal plasticity (kindling) in the rat dentate gyrus. 270 74

To investigate the molecular changes underlying kindling epileptogenesis in the rat hippocampus, the expression levels of the genes encoding for 13 different gamma-aminobutyric acid type-A receptor (GABAAR) subunits were measured in hippocampal principal neurons using in situ hybridization techniques and semi-quantitative analysis of the autoradiograms. Schaffer collateral-commissural pathway kindled rats were investigated at three different stages of kindling acquisition, at 24 h after the last seizure and at long-term (28 days) after termination of kindling stimulations. Changes were distinct for the different subunits in the three analyzed regions (CA1, CA3, fascia dentata) and also different for the various kindling stages. In all hippocampal areas at the early phases of kindling epileptogenesis, before the appearance of generalized seizures, an increase was found of those transcripts that constituted the majority of the expressed variants in control animals (alpha 1, alpha 2, alpha 4, beta 1, beta 2, beta 3, gamma 2/gamma 2L mRNA). In these stages, the increased levels of different variants in the granular neurons of the fascia dentata were more pronounced when compared to the pattern of changes in pyramidal cells of CA1 and CA3. In fully kindled animals, the expression levels of several subunits returned to control levels, whereas beta 3 and gamma 2/gamma 2L mRNA expression was still significantly enhanced in all areas. At long-term, few changes were encountered. The long-splice variant of gamma 2 was decreased within pyramidal and granular neurons while the total level of gamma 2 mRNA was not different from controls. The increased GABAAR subunit expression in the fascia dentata may underly the reported increased GABAAR ligand binding and the increased GABA mediated inhibition. However, the decreased GABAAR binding and the attenuation of GABAergic inhibition in CA1, could not be explained by a decrement of receptor subunit expression.
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PMID:Expression of GABAA receptor subunit mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study. 747 32

Cocaine is an extremely addictive local anesthetic which can produce stimulation of the sympathetic nervous system due to the inhibition of catecholamine reuptake at the synaptic junction. Because of the rapid metabolism of cocaine, the probability of a patient presenting to the operating room with acute intoxication is unlikely. However, the physiological effects of chronic cocaine abuse on various organ systems have an impact on anesthesia management. A preoperative review of major organ systems is essential. Selective beta 1 antagonists (i.e., esmolol) may need to be titrated with a direct vasodilator (i.e., nitroprusside) to manage hypertension and tachycardia. The nonselective beta antagonist effects of labetalol are much more potent than its alpha antagonist effects, which could result in unopposed alpha vasoconstriction. In addition, the equal affinity of the alpha adrenergic antagonist, phentolamine, for both alpha 1 and alpha 2 receptors may result in significant tachycardia. Nitroglycerin has also been used in management of hypertension associated with coronary vasoconstriction. There is controversy regarding management of ventricular dysrhythmias and asystole. Lidocaine is an amide local anesthetic that may have addictive effects, in the presence of cocaine, which may lower the seizure threshold. In addition, the use of epinephrine to treat asystole is controversial in the presence of a state of excess catecholamines induced by cocaine. General anesthesia may include barbiturates, nitrous oxide, and opioids. Inhalational agents may be used with caution due to their myocardial depressant effects. Regional anesthesia may be a good choice if coagulopathies and hypovolemia are corrected before the procedure.
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PMID:Anesthetic management of the cocaine abuse patient. 750 43

Changes in gene expression after kindled seizures were examined using microdissection of discrete brain areas and Northern and slot blot analyses. Experimental animals were kindled with either of two protocols: (1) a paradigm in which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal electrodes (12 stimulations every other day for 4 days) and (2) a traditional approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last kindled seizure. We first examined the possibility that kindling may affect transcription of mRNA for neurotransmitter receptors. We found significant decreases (22-58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2, -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex 24 h but not 30 days after rapidly kindled seizures. However, changes in GABA receptor alpha 1, alpha 2, alpha 4 or beta 1 mRNAs were not observed in any brain region 30 days after traditional kindling or 24 h after rapidly kindled seizures. In addition, we tested whether changes in the expression of proenkephalin could be detected after kindling. We found significant increases (1.7-10 fold) in proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures. Our findings suggest that changes in glutamate receptor and proenkephalin gene expression are robust, acute sequelae to kindled seizures and may be involved in kindling.
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PMID:Changes in glutamate receptor and proenkephalin gene expression after kindled seizures. 752 14

Through a study of cloned nicotinic receptors expressed in Xenopus oocytes, we provide evidence that alpha-conotoxin ImI, a peptide marine snail toxin that induces seizures in rodents, selectively blocks subtypes of nicotinic acetylcholine receptors. alpha-Conotoxin ImI blocks homomeric alpha 7 nicotinic receptors with the highest apparent affinity and homomeric alpha 9 receptors with 8-fold lower affinity. This toxin has no effect on receptors composed of alpha 2 beta 2, alpha 3 beta 2, alpha 4 beta 2, alpha 2 beta 4, alpha 3 beta 4, or alpha 4 beta 4 subunit combinations. In contrast to alpha-bungarotoxin, which has high affinity for alpha 7, alpha 9, and alpha 1 beta 1 gamma delta receptors, alpha-conotoxin ImI has low affinity for the muscle nAChR. Related Conus peptides, alpha-conotoxins MI and GI, exhibit a distinct specificity, strictly targeting the muscle subtype receptor but not alpha 7 or alpha 9 receptors. alpha-Conotoxins thus represent selective tools for the study of neuronal nicotinic acetylcholine receptors.
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PMID:alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors. 765 51


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