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)

From day 1 to day 3, the protein intake of this neonate was restricted to 1 g/kg/d. It included a) essential amino acids (i.e. histidine, lysine, threonine, tryptophan), b) arginine (1,000 mg/d), c) alphaketoisovaleric 500 mg/d, alpha-ketoisocaproic (500 mg/d), alphaketobetamethylvaleric (500 mg/d), alphaketogammamethylthiobutyric (200 mg/d), betaphenylpyruvic (400 mg/d) acids. 250 mg/kg/d of sodium benzoate were given. Caloric and water intakes were 120 cal/kg/d and 120 ml/kg/d respectively. Afterwards, this procedure was modified according to clinical and biological data including serum ammonia and amino acid levels. Alpha-ketonic acid absorption and metabolism were studied on day 29. Both were fast. The detection of alloisoleucine, which is not metabolized was the consequence of the use of alphaketobetamethylvaleric acid. Until the age of 21 months, clinical and metabolic status was satisfactory. At this time, repeated seizures without metabolic failure were accompanied by psychomotor damages.
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PMID:[Treatment of citrullinemia. Apropos of a case followed from birth. Importance of alpha-ketonic acids]. 344 58

Extracellular levels of amino acids were estimated in dialysates of the rat striatum that were collected 1, 2, and/or more than 5 days after surgery, before (resting release) and during exposure to high K concentrations (50 mM) or electroconvulsive shocks. The resting release of several amino acids (Glu, Asn, Thr, Tau, Tyr, Gly, and Ala) was higher 9 days as compared to 1 day after surgery. In the 1-day preparation the resting release correlated highly with that observed with push-pull cannulas. The correlation with the tissue content of the amino acids was high only when they were divided into two groups (putative transmitters and metabolic intermediates). High K exposure produced increased output of Ala, ethanolamine (Eam), Asp, Glu, Tau, and Gly and a decrease in the egress of Gln 1 or 2 days after surgery. The effects on Asp and Glu had disappeared, and that on Gln reversed after 4-9 days. Electrically induced convulsions produced increased output of Ala, Gln, and Eam 1 or 2 days and 2 weeks after implantation of the probe. Changes were seen not only during but also (and some cases even more prominent) after the seizure. This study shows the usefulness of dialysis to monitor extracellular transmitter amino acids in the striatum of conscious rats (also bilateral dialysis was possible) for only a limited time after implantation of the probe. The dialysis method is suitable for longer time, when metabolic changes in amino acids are to be followed. In addition to transmitter release, glycolysis can be monitored by the measurement of Ala in the dialysate.
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PMID:Amino acids in rat striatal dialysates: methodological aspects and changes after electroconvulsive shock. 404 52

In rabbits, generalized seizures were induced by methoxypyridoxine, and changes in amino acid concentrations of 15 brain regions were investigated before seizure onset and during the course of sustained epileptiform activity. As previously reported, gamma-aminobutyric acid (GABA) concentration decreased preictally in most regions. At the same time, taurine level was elevated in the hypothalamus, thalamus, hippocampus, caudatum, and frontal cortex. After 90 min of seizures, it was significantly decreased in the hypothalamus, periaqueductal grey, substantia nigra, frontal cortex, and cerebellum. Glycine content was reduced preictally only in the substantia nigra; after seizure onset its concentration rose in all brain areas. Glutamate content in the frontal cortex decreased before seizure onset; after 1.5 h of seizures, its concentration in cerebellum, caudatum, and hippocampus was reduced. Aspartate level was decreased in most areas after sustained seizures; in putamen, however, it was elevated. In contrast, glutamine content increased preictally in the superior colliculus and in all brain areas by approximately 200% after 90 min of seizures. Alanine and valine content also rose markedly in most brain areas after prolonged seizures, and threonine showed the same tendency. The single brain regions were observed to respond to methoxypyridoxine in highly individualistic ways. For example, the glycine content of the substantia nigra, which is believed to utilize this amino acid as a neurotransmitter, decreased preictally. The potential importance of the superior colliculus in seizure induction is considered in view of the early rise in glutamine level. The antagonistic preictal behavior of taurine and GABA is discussed with respect to synthesis, uptake from the blood, and antiepileptic properties.
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PMID:Alterations in the content of amino acid neurotransmitters before the onset and during the course of methoxypyridoxine-induced seizures in individual rabbit brain regions. 613 13

The amygdalas of rats were stimulated daily to produce kindled epilepsy. Superfusion of the ipsilateral ventricle allowed collection of amino acids before, during and after stimulation. At the stage where stimulation evoked full seizures there was a correlated increase in the extent of glutamate release. Other amino acids, including aspartate, showed no significant changes at this time. Aspartate, threonine and serine showed smaller responses not significantly different from those seen at the pre-kindled stage. Antagonists of excitatory amino acids (omega-phosphono-alpha-amino dicarboxylic acids) effectively antagonized both the behavioral and electrical components of the kindled seizures.
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PMID:The kindled amygdala model of epilepsy: anticonvulsant action of amino acid antagonists. 613 23

The respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.
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PMID:Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats. 630 57

Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.
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PMID:Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice. 631 93

To clarify the molecular mechanism of neuronal bursting activity of seizures, we have constructed a cDNA library from mouse cerebrum cortex-derived cells treated with pentylentetrazole (PTZ), one of the convulsant drugs. Using a differential screening technique, several cDNA clones whose expressions change with PTZ-treatment were obtained. Among these clones, SEZ-6 was characterized by increased expression with PTZ. Detailed northern analysis showed that expression of SEZ-6 was limited to the brain and increased by the administration of PTZ not only in in vitro cultured cells but also in vivo. Analysis of SEZ-6 cDNA revealed multiple motifs, including typical signal sequence, threonine-rich domain, five copies of short consensus repeats (SCRs) or sushi domain (complement C3b/C4b binding site), two repeated sequences which were partially similar to the CUB domain or complement C1r/s-like repeat, one transmembrane domain and a short cytoplasmic segment in the C-terminal region. Although many proteins with multiple SCRs or CUB domains other than complement-related proteins have been found, this is the first report about a brain-specific cDNA which encodes membrane protein with both SCRs and CUB domain-like segments. Based on these findings, it is evident that SEZ-6 encodes a novel type of protein which may be related to seizure.
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PMID:Cloning and expression of SEZ-6, a brain-specific and seizure-related cDNA. 772 19

Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.
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PMID:Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy. 809 92

MKP-1 (also known as CL100, 3CH134, Erp, and hVH-1) exemplifies a class of dual-specificity phosphatase able to reverse the activation of mitogen-activated protein (MAP) kinase family members by dephosphorylating critical tyrosine and threonine residues. We now report the cloning of MKP-3, a novel protein phosphatase that also suppresses MAP kinase activation state. The deduced amino acid sequence of MKP-3 is 36% identical to MKP-1 and contains the characteristic extended active-site sequence motif VXVHCXXGXSRSXTXXXAYLM (where X is any amino acid) as well as two N-terminal CH2 domains displaying homology to the cell cycle regulator Cdc25 phosphatase. When expressed in COS-7 cells, MKP-3 blocks both the phosphorylation and enzymatic activation of ERK2 by mitogens. Northern analysis reveals a single mRNA species of 2.7 kilobases with an expression pattern distinct from other dual-specificity phosphatases. MKP-3 is expressed in lung, heart, brain, and kidney, but not significantly in skeletal muscle or testis. In situ hybridization studies of MKP-3 in brain reveal enrichment within the CA1, CA3, and CA4 layers of the hippocampus. Metrazole-stimulated seizure activity triggers rapid (<1 h) but transient up-regulation of MKP-3 mRNA in the cortex, piriform cortex, and some amygdala nuclei. Metrazole stimulated similar regional up-regulation of MKP-1, although this was additionally induced within the thalamus. MKP-3 mRNA also undergoes powerful induction in PC12 cells after 3 h of nerve growth factor treatment. This response appears specific insofar as epidermal growth factor and dibutyryl cyclic AMP fail to induce significant MKP-3 expression. Subcellular localization of epitope-tagged MKP-3 in sympathetic neurons reveals expression in the cytosol with exclusion from the nucleus. Together, these observations indicate that MKP-3 is a novel dual-specificity phosphatase that displays a distinct tissue distribution, subcellular localization, and regulated expression, suggesting a unique function in controlling MAP kinase family members. Identification of a second partial cDNA clone (MKP-X) encoding the C-terminal 280 amino acids of an additional phosphatase that is 76% identical to MKP-3 suggests the existence of a distinct structurally homologous subfamily of MAP kinase phosphatases.
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PMID:MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase. 862 80

Repeated subthreshold stimulation of limbic brain areas increases seizure susceptibility in experimental models of epilepsy. In addition, acute dietary indispensable amino acid (IAA) deficiency activates the anterior piriform cortex (APC), a seizure-prone limbic brain area in the rat. Based on these two findings, we hypothesized that activation of the APC by chronic exposure to IAA-deficient diets might increase seizure susceptibility. Several nonessential amino acid neurotransmitters are important in seizures, but deficiencies of nontransmitter IAAs have not been well studied in seizure models. In four trials, we made injections of pentylenetetrazole intraperitoneally or of bicuculline into the APC in histidine-, isoleucine-, or threonine-deficient rats and controls. Increased susceptibility to seizures in the deficient animals was observed as increased severity of the seizures, decreased threshold for the dose of the chemostimulant and time to seizure, or a combination thereof. Pair-fed controls showed that this effect was not due to an energy deficit. This novel but robust finding suggests that IAA deficiency may increase vulnerability to seizures by repeated activation of the APC.
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PMID:Indispensable amino acid deficiency and increased seizure susceptibility in rats. 876 Jan 99


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