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)

In 14 patients operated upon for focal cerebral seizures under local anesthesia, cortical electrical activity was compared with the levels of nicotinamide adenine dinucleotide (NADH) observed fluorometrically. NADH levels fell 3 to 15% in response to 5-second intervals of cortical stimulation in 42 of 70 observations. Although a rough correlation was seen between the quantity of current delivered (milliamperes X seconds) and the NADH decrease, this varied from case to case. The presence of cortical afterdischarge often, but not invariably, corresponded to a greater percentage of change in the NADH levels. Averaging the NADH response to sporadic interictal epileptiform discharges failed to demonstrate concomitant NADH reductions. A similar lack of change was seen in four patients in whom low frequency spike foci were induced by topically applied penicillin in cortex destined for excision. Preliminary studies of the topography of spread of NADH change after cortical stimulation indicate that this is usually asymmetrical in human epileptogenic cortex. Under experimental conditions in cats, it seemed possible to differentiate primary from projected epileptiform activity, in that the projected activity had little or no concomitant fall in the NADH level after the electrographic spike. Pathological examination of the excised sites of NADH recording showed, with one exception, fibrous astrocytic transformation of the central cortex layers.
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PMID:Fluorometric monitoring of NADH levels in cerebral cortex: preliminary observations in human epilepsy. 21 33

We report the clinical, electroencephalographic, neurophysiologic, and neuroimaging findings in eight children with infant-onset progressive myoclonus epilepsy, all of whom had muscle biopsies performed as as part of the diagnostic evaluation. Each child had myoclonic seizures, generalized tonic-clonic seizures, and neurologic regression or marked developmental delay. Four children died before 3 years of age. Electroencephalograms in seven children showed an abnormally slow background with bilateral multifocal paroxysmal discharges but no burst suppression pattern or photoparoxysmal response. Muscle biopsy specimens were submitted for histopathology and respiratory-chain enzyme studies. Nonspecific abnormalities on light microscopy or electron microscopy were found in seven samples, including increased subsarcolemmal deposits of mitochondria or morphologic mitochondrial changes, but no ragged-red fibers were seen. Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway. This study has shown that infant-onset progressive myoclonus epilepsy can be distinguished from other myoclonic epilepsy syndromes of infancy by clinical and electrographic features. Furthermore, respiratory-chain enzyme defects are a relatively common cause of infant-onset progressive myoclonus epilepsy. The absence of ragged-red fibers on muscle histopathology does not preclude a mitochondrial enzyme abnormality.
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PMID:Infant-onset progressive myoclonus epilepsy. 2198 53

The influence of delta-sleep inducing peptide (DSIP) upon seizures induced by corazol, bicuculline, picrotoxin, strychnine, thiosemicarbazide were investigated in experiments on F1(CBA X C57 BL/6) mice. It was shown that DSIP increased the latency of first seizure manifestation which were induced by corazol, bicuculline and picrotoxin and also resulted in a suppression of seizure severity of corazol and bicuculline induced seizures. Anticonvulsant action of DSIP was evident under the condition of the mild severity seizures development. The effect of DSIP was mostly pronounced in range of its doses from 10 to 100 mcg/kg. DSIP when combined with phenobarbital, carbamazepine, diphenylhydantoin or nicotinamide enhanced the antiepileptic effects of these anticonvulsant drugs.
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PMID:[Effect of delta sleep-inducing peptide, anticonvulsant preparations and nicotinamide on generalized seizure activity]. 252 23

gamma-Aminobutyric acid (GABA) modulation of triazolam and nicotinamide binding to benzodiazepine (BDZ) receptors in vitro was compared with the neurotoxicity and anticonvulsant activity of these two drugs in vivo. GABA had no significant effect on the inhibitory potency of triazolam in [3H]flunitrazepam receptor binding, whereas GABA decreased the inhibitory potency of nicotinamide. When administered to mice, both triazolam and nicotinamide exhibited neurotoxicity by the rotorod test and anticonvulsant activity by the pentylenetetrazol seizure threshold test. This suggests that GABA modulation of the receptor binding of a BDZ ligand in vitro is not a reliable predictor of the pharmacologic activity of the ligand.
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PMID:gamma-Aminobutyric acid modulation of benzodiazepine receptor binding in vitro does not predict the pharmacologic activity of all benzodiazepine receptor ligands. 285 62

Acute experiments on mice were made to investigate the anticonvulsant activity of diazepam and its combination with nicotinamide in experimental seizures induced by corazol, picrotoxin, bicucullin and thiosemicarbazide. It was shown that diazepam (0.2-1.6 mg/kg) produced a dose-dependent anticonvulsant effect in all models under study. Nicotinamide (250 mg/kg) substantially reduced the animals' lethality and seizure manifestations induced by picrotoxin and completely protected some of the animals from the bicucullin-induced seizures. Nicotinamide (250 mg/kg) potentiated the anticonvulsant effect of diazepam in all the experimental seizures under study. Micotinamide had a more pronounced effect in respect of the protection of the animals from tonic seizures as compared with clonic ones. The data suggest that the mechanisms of the anticonvulsant action of nicotinamide are mediated via the GABA-benzodiazepine receptor complex.
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PMID:[Effect of diazepam and nicotinamide on convulsive activity of various types]. 293 4

The anticonvulsive action of diazepam, carbamazepine, sodium valproate and their combinations with pyridoxal-5-phosphate, nicotinamide, and alpha-tocopherol were investigated in acute experiments on mice with corazole-induced seizures. Diazepam (0.5 mg/kg), carbamazepine (50 mg/kg) and sodium valproate (200 mg/kg) were shown to reduce convulsive intensity and lethality. Vitamins nicotinamide (250 mg/kg), pyridoxal-5-phosphate (10 mg/kg) and alpha-tocopherol (100 mg/kg) potentiated anticonvulsive action of the above antiepileptic drugs. The results of the investigation suggest the efficacy of pathogenetic therapy and give new evidence of the advisability of using vitamins in combination with synthetic anticonvulsive drugs.
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PMID:[Effect of diazepam, carbamazepine, sodium valproate and their combinations with vitamin preparations on epileptic activity]. 293 95

The effect of pretreatment with drugs on generalized clonic-tonic seizures induced by intracerebroventricular (i.c.v.) administration of the endogenous convulsant quinolinic acid (QUIN, 50 micrograms) was studies in rats. Of the inhibitory amino acids tested, only 1-glycine (50 and 100 micrograms, i.c.v.) diminished the number of animals with seizures while taurine and GABA were ineffective. Of the kynurenine metabolites, only kynurenic acid (50 micrograms, i.c.v.) prevented seizures and lethality. Picolinic acid, nicotinic acid and nicotinamide were ineffective. The standard anticonvulsants phenobarbital, diphenylhydantoin and primidone were effective antagonists of QUIN-induced seizures at doses which did not influence pentylenetetrazol seizures. However, the only drug which completely prevented QUIN-induced seizures was diazepam (10 mg/kg). It also prevented pentylenetetrazol seizures in rats in a four times lower dose. The GABA derivatives sodium hydroxybutyrate and phenibut (beta-phenyl-GABA), which are effective QUIN-antagonists in mice, were found to be ineffective in rats. Species differences between rats and mice in the efficacy of antagonists QUIN are discussed.
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PMID:Antagonism of seizures induced by the administration of the endogenous convulsant quinolinic acid into rat brain ventricles. 294 Mar 35

Vitamin B-6 deficient rats exhibit changes in behavior, sensory function, and other nervous system abnormalities such as convulsive seizures and motor disturbances. Sensorimotor reactivity was evaluated quantitatively by measuring auditory and tactile startle responses in 12 week old female Long-Evans rats fed a diet devoid of added vitamin B-6 (DEF) or a control diet, either ad lib (AL-CON) or pair-fed to deficient rats (PF-CON). Deficiency was confirmed with a tryptophan-load test administered to a separate group of rats fed simultaneously according to the same protocol. At week 18, body weight and feed efficiency were different among groups (p less than 0.001), and were lowest in DEF. Amplitude of response to both acoustic and tactile stimuli was depressed in DEF compared to both control groups, which generally did not differ in response. This effect was seen most dramatically in responses to the acoustic stimulus (p = 0.034), and especially to the first presentation (p = 0.017). Latency to maximum response was not affected by diet. Possible mechanisms for this nervous system abnormality, not previously reported in vitamin B-6 deficiency, are discussed.
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PMID:Attenuation of acoustic and tactile startle responses of vitamin B-6 deficient rats. 362 44

The purpose of the present study was to elucidate the importance of extracellular adenosine (ADO) in the regulation of cerebrocortical microcirculation during rest, hypoxia, and brain activation. Cerebrocortical microcirculation and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were measured by surface fluororeflectometry through a cranial window. Arterial hypoxia and brain activation were produced by respirating the animals with a gas mixture containing 6-7% O2 and by injecting 4-6 mg/kg metrazol into the lingual artery, respectively. These reactions were used as test before and after theophylline (THEO) treatment. In some of the experiments only the cortical area beneath the cranial window was treated with THEO (10(-4) M), in others 2 X 10(-4) mol/kg THEO was injected intraperitoneally. Potency of THEO in antagonizing the cerebral blood flow (CBF) increasing effect of topically applied ADO was also tested. It was found that superfusion of the brain cortex with artificial cerebrospinal fluid (mock CSF) containing 10(-4) M THEO does not alter resting CBF, but inhibits the CBF increasing effect of 10(-6) M and 10(-5) M ADO by approximately 70% and 40%, respectively. Intraperitoneally injected THEO increased CBF by approximately 60%, which has been attributed mostly to its action on the systemic circulation. Under control conditions, arterial hypoxia and epileptic seizures increased CBF by approximately 150% and 300%, respectively. Since neither topical nor systemic THEO treatment altered the vasodilatory and CBF increasing potency of arterial hypoxia and attenuated these effects of epilepsy slightly, it was concluded that extracellular ADO is not a critical factor in the regulation of cerebrocortical microcirculation.
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PMID:Effect of theophylline treatment on the functional hyperaemic and hypoxic responses of cerebrocortical microcirculation. 382 55

Investigation of the actions of the benzodiazepines has provided insights into the neurochemical mechanisms underlying anxiety, seizures, muscle relaxation, and sedation. Behavioral, electrophysical, pharmacological, and biochemical evidence indicates that the benzodiazepines exert their therapeutic effects by interacting with a high-affinity binding site (receptor) in the brain. The benzodiazepine receptor interacts with a receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter, and enhances its inhibitory effects. The benzodiazepine receptor may also interact with endogenous substances and several naturally occurring compounds, including the purines and nicotinamide, are candidates for this role. Both the purines and nicotinamide possess some benzodiazepine-like properties in vivo, although further work will be required to confirm their possible roles as endogenous benzodiazepines.
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PMID:Receptors for the age of anxiety: pharmacology of the benzodiazepines. 610 Dec 94


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