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

The aim of this investigation was to determine the incidence of seizure activity in the acute phase following traumatic brain injury. Compression contusion trauma was produced in the right parietal cortex in 19 artificially ventilated rats. Electroencephalographic recordings were carried out in 17 of the animals for 2 h following the impact. The extracellular levels of neuroactive amino acids were simultaneously monitored in 9 of the experiments using microdialysis. In 14 of the 17 animals a generalized seizure activity with an average duration of 59 s (range 30-101 s) was recorded. The mean time lag between trauma and seizure onset was 67 s (range 26-90 s). The seizure activity was consistently followed by post-ictal depression. The trauma was accompanied by a transient increase of aspartate, taurine, glutamate and glycine, in decreasing rank order. The seizure activity occurred when the levels of these neuroactive amino acids were elevated. It is concluded that the high incidence of seizure activity observed may be an important factor contributing to secondary ischemia after traumatic brain injury. Aspartate and glutamate, potentiated by glycine, may play a role in post-traumatic seizure activity.
 ...
PMID:Epileptic seizure activity in the acute phase following cortical impact trauma in rat. 818 Aug

The metabolism of GABA and other amino acids was studied in the substantia nigra, the hippocampus and the parietal cortex of rats following microinjections of GAMMA-vinyl-GABA during status epilepticus induced by lithium and pilocarpine. GABA metabolism showed striking regional variations. In controls, both GABA concentration and rate of GABA synthesis were highest in the substantia nigra and lowest in cortex, as expected. In substantia nigra, status epilepticus resulted in a 2 1/2 fold decline in the rate of GABA synthesis and in a 307% increase in the turnover time of the GABA pool. In hippocampus, the rate of GABA synthesis was not altered significantly, but the turnover time of the GABA pool was 284% of controls, and the size of that pool increased to 208% of controls. By contrast, in cortex, where seizure activity is limited in this model, the rate of GABA synthesis increased to 230% of controls while pool size and turnover time did not change. Aspartate concentration decreased in all three brain regions. These data suggest that the observed reduction of the rate of GABA synthesis in substantia nigra could play a key role in seizure spread in this model of status epilepticus.
 ...
PMID:GABA metabolism in the substantia nigra, cortex, and hippocampus during status epilepticus. 847 71

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.
 ...
PMID:A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis. 893 4

Dichloromethane, methanol and water extracts of Viscum sapense L.f., of the Loranthaceae family, were tested for antimicrobial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Methanol extract was also tested for activity against seizures in albino mice induced by pentylenetetrazole (PTZ), bicuculline and N-methyl-DL-aspartic acid (NMDLA). Methanol extract of V. capense inhibited the growth of S. aureus. Methanol extract also protected the mice against PTZ- and bicuculline-induced tonic seizures but did not significantly alter NMDLA-induced tonic seizures. The data indicate that the extract of V. capense has antibacterial activity against S. aureus and also anticonvulsant activity.
 ...
PMID:Antimicrobial and anticonvulsant activities of Viscum capense. 970 15

A rational, chemical, synthetic effort to identify promising low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists for use as antiepileptic drugs led to the discovery of AR-R 15035AR, or [RS]-alpha-phenyl-2-pyridine-ethanamine.2HCl. Chiral separation followed by intensive in vivo screening resulted in the selection of the [S] enantiomer, AR-R 15896AR, as the best compound for further preclinical development. AR-R 15896AR prevented tonic seizures in rodents for up to 6 to 8 h in response to maximal electroshock (MES), 4-aminopyridine, bicuculline, or strychnine, as well as characteristic seizures following injections of N-methyl-DL-aspartic or kainic acids. AR-R 15896AR was ineffective in two kindling models of epilepsy, did not produce tolerance to MES, and was devoid of proconvulsant and phencyclidine-like properties in mice and rats, respectively. Therapeutic indices for AR-R 15896AR were comparable to or exceeded those for standard anticonvulsants. Orally administered AR-R 15896AR rapidly entered the rat brain and was eliminated in parallel from the plasma and plasma-free compartment. A dose-response relationship between plasma and brain levels after p.o. or i.v. administration of AR-R 15896AR and protection against MES was highly correlative. The time course for loss of protection against MES mirrored the elimination of the compound from brain and plasma. The total brain concentration (25 microM) of drug at the ED50 value (approximately 3 mg/kg) for protection against MES seizures was consistent with the reported affinity of AR-R 15896AR at the N-methyl-D- aspartic acid binding site (IC50 value = 1.3 microM). The present findings demonstrated the attractiveness of AR-R 15896AR as a candidate for further development to treat epilepsy.
 ...
PMID:[S]-AR-R 15896AR-A novel anticonvulsant: acute safety, pharmacokinetic and pharmacodynamic properties. 986 62

The effects of drugs affecting GABA and glutamic acid receptors on theophylline-induced seizures were investigated in mice. Theophylline elicited tonic seizures in mice in a dose dependent manner. Muscimol, DABA and AOAA significantly prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. Baclofen significantly delayed the onset of the tonic seizures induced by theophylline. Bicuculline and picrotoxin significantly shortened the onset and significantly increased the incidence of seizures induced by a low dose of theophylline and also significantly antagonized muscimol-attenuating effect against theophylline seizures. N-methyl-DL-aspartic acid significantly shortened the onset and significantly increased the incidence of seizures elicited by a low dose of theophylline. D-(-)-2-amino-phosphonopentanoic acid effectively delayed the onset and significantly decreased the incidence of seizures elicited by theophylline and also significantly antagonized the potentiating effect of N-methyl-DL-aspartic acid on seizures induced by a low dose of theophylline. Dextromethorphan and ketamine profoundly shortened the onset of theophylline-induced seizures. Clonidine effectively prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. These data indicate that GABA(A) and N-methyl-D-aspartic acid receptors may mediate theophylline-elicited tonic seizures in mice.
 ...
PMID:Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice. 1021 93

Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children with various neurological disorders was performed with high performance liquid chromatography (HPLC). Glutamate increased in patients with bacterial meningitis, aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis and seizure disorders. Glycine increased in both bacterial and aseptic meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory amino acids are richly distributed in brain tissue and are related to neuron activity. Changes in amino acid levels in the CSF may reflect the pathologic state and severity of brain insults, and may be useful in monitoring disease processes. Further study is necessary to determine whether CSF aminos acid levels have a role in practical clinical application.
 ...
PMID:Excitatory and inhibitory amino acid levels in the cerebrospinal fluids of children with neurological disorders. 1091 May 89

Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death, in response to physical activity or emotional stress. Two modes of inheritance have been described: autosomal dominant and autosomal recessive. Mutations in the ryanodine receptor 2 gene (RYR2), which encodes a cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel, were recently shown to cause the autosomal dominant form of the disease. In the present report, we describe a missense mutation in a highly conserved region of the calsequestrin 2 gene (CASQ2) as the potential cause of the autosomal recessive form. The CASQ2 protein serves as the major Ca(2+) reservoir within the SR of cardiac myocytes and is part of a protein complex that contains the ryanodine receptor. The mutation, which is in full segregation in seven Bedouin families affected by the disorder, converts a negatively charged aspartic acid into a positively charged histidine, in a highly negatively charged domain, and is likely to exert its deleterious effect by disrupting Ca(2+) binding.
 ...
PMID:A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. 1170 30

Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90 mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg). However, all the doses of aqueous extract of L leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.
 ...
PMID:Anticonvulsant activity of aqueous extract of Leonotis leonurus. 1204 62

Hughlings Jackson at the turn of the century defined epilepsy as a disorder originating in a "morbid nutrition" of the neuron. With the advances in modern neurochemistry, it is becoming increasingly clear that a chronic seizure predisposition or a lowering of the brain's discharge threshold can be demarcated by a number of biochemical markers. They include a tendency for an increased release of glutamate with or without GABAergic impairment, (intra)neural tissue alterations in water redistribution/osmolarity or other distortions of the cytoarchitecture, and an elevation of ionic calcium inside the cell. These changes are dominantly shared parameters of the seizure prone brain. Magnetic resonance spectroscopy (MRS) shows that cerebral levels of glutamate + glutamine (Glx) are increased interictally in epileptogenic regions in human partial epilepsy; other findings using this technique suggest damage to (cellular/mitochondrial) membranes, denoted by N-acetyl-aspartic acid (NAA) changes and a decreased energy capability. The merging of previous in vitro and ex vivo findings in neurophysiology and neurochemistry with magnetic resonance spectroscopy technology provides a powerful new methodology to interpret and to obtain clinical insight into the metabolic alterations that underlie an epileptogenic process. In this review some of these basic neurochemical and electrophysiological mechanisms are discussed. In addition, certain adjuncts to established antiepileptic drug therapy are suggested in the hope that over the long term they may help in correcting the primary metabolic deficits.
 ...
PMID:Metabolic parameters of epilepsy: adjuncts to established antiepileptic drug therapy. 1260 9


<< Previous 1 2 3 4 5 6 7 8 9 Next >>