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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review examines the interaction of pyridoxal phosphate with select neuroendocrine and neuropharmacological systems and their health related therapeutic implications. Vitamin B6 and its vitamers can be involved in many interactions with a number of drugs as well as the actions of various endocrines and neurotransmitters. Nutritional deficiencies, particularly of vitamins and proteins, can affect the manner in which drugs undergo biotransformation and thus may modify the therapeutic efficacy of certain drugs. In addition to pyridoxine deficiency adversely affecting drug actions, improper supplementation with viatmin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridocxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions amony pyridoxine vitamers, both phosphorylated and nonphosphorylated, are briefly discussed, particularly concerning their pharmacokinetic properties. The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pryidoxine hydrochloride prevents or stops these seizures. The acute ingestion of excessive monosodium glutamate will, in some persons, cause a group of symptoms, including headache, weakness, stiffness, and heartburn, collectively known as the "Chinese Restaurant Syndrome." These symptoms can be prevented by prior supplementation with vitamin B6. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate. Therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phospate appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase. Treatment with daily pyridoxine can reverse a state of depression induced in women who take oral contraceptives (OCs). 1 hypothesis to explain this effect is that the OC is somehow causing a deficiency of seroton serotonin in the brain and that the vitamin B6 helps to overcome this deficiency through the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, pyridoxal phosphate in physiological concentrations seems to function as an endogenous "down regulator" of several receptor sites, including estrogen, progesterone, and androgen.
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PMID:Drug-pyridoxal phosphate interactions. 608 25

The cerebral concentrations of pyridoxal-5'-phosphate and divalent transition metal ions (Cu2+ and Zn2+) are appreciably higher in the seizure-susceptible strain of mouse (DBA/2J) than those in normal strains (CBA/Ca and Parkes ). By injecting metal ions intracranially and pyridoxal-5'-phosphate intraperitoneally, we could render the normal mouse prone to sound-induced epilepsy. The behaviour of the treated seizure-susceptible strain of mouse. The levels of glutamate and aspartate in its inferior colliculus were elevated and the concentration of gamma-aminobutyrate was lowered. Glutaminase inhibitors, 6-diazo-5-oxo-L-norleucine (DON) and 0-diazo-acetyl-L-serine (azaserine), and a transaminase inhibitor, 4-amino-3- isoxazolidone (L-cycloserine), when injected intraperitoneally, protected the seizure-susceptible mouse from undergoing convulsions, whereas pyridoxal-5'-phosphate and methionine sulphoximine, a glutamine synthetase inhibitor, exacerbated its epileptic condition. We propose a possible sequence of biochemical events associated with susceptibility to audiogenic seizures.
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PMID:Studies on sound-induced epilepsy in mice. 614 59

The effects of seizures on the cerebral and peripheral metabolism of essential metals were studied in mice. Acute and chronic seizures were produced either by electroshock (ES) or by a systemic convulsant. Organ and subcellular distribution of 54Mn and 65Zn were determined prior to and at different intervals after seizure cessation. In mice shocked for 21 days, the concentrations of manganese, zinc, magnesium, and copper were determined in selected tissues. Sham-seizured mice served as controls. When 54Mn was injected after a single ES, the isotope's retention increased in the liver by 67% (P less than 0.01) and decreased in the brain and carcass by 53 and 42%, respectively (P less than 0.01). Repeated ES further augmented these effects (P less than 0.01). These changes diminished as a function of time to the animal's recovery from ES. Liver and regional brain fractionations revealed significant perturbation in the intercellular partition of 54Mn, suggesting increased metal utilization. Brain and liver 65Zn were not affected by ES. Manganese content increased in the liver by 67% (P less than 0.01) and decreased in whole brain by 16.5% (P less than 0.01), after chronic ES. Cortical manganese and hypothalamic magnesium were the principal sites of loss. Small (12 to 13%), but significant elevations of magnesium were found in liver and skeletal muscle (P less than 0.05). Copper increased in muscle by 26% (P less than 0.02). Seizures selectively altered the normal brain and extracerebral distribution of essential metals which may lead to regional metal deficiency or excess. These changes were linked to the metabolic consequences of convulsive activity and may be relevant to seizure control and electroshock therapy in man.
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PMID:Generalized seizures alter the cerebral and peripheral metabolism of essential metals in mice. 662 11

Brain copper and zinc levels were determined in 21-day-old and "adult" C3HeB/FeJ quaking mice and in normal littermate controls. Expressed per gram dry weight of brain, copper was increased 84% over normal mice at 21 days after birth, but was not significantly different from normal in the adults. Zinc was increased 23 to 24% at both ages. At both ages, brains from quaking mice had a significantly reduced content of solids, indicating increased water content in the mutant brain. Our study is the first to report copper and zinc content as a measure of both wet and dry brain weights. Our results indicate abnormal copper content in the quaking mutant. The relationship between copper content and other aspects of the quaking phenotype, including its seizure behavior and myelin deficit, remain to be established.
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PMID:Altered brain copper and zinc content in quaking mice. 662 15

The role of divalent transition metal ions in neural function is poorly understood. In excess, these ions are associated with neurological disorders such as Wilson's disease, Pick's disease and epileptic seizures. We suggest that zinc ions, which are contained in nerve terminals, are extruded into the extracellular space during neuronal activity. Excessive levels of zinc may be released during intense neuronal activation, and contribute to the paroxysm and toxic damage observed. Zinc ions are contained in high concentrations in mossy fibres of the hippocampal formation, and it is the postsynaptic neurones of these fibres which are most susceptible to the toxic effects of kainic acid, a potent convulsant, or to chronic exposure to organometallic compounds. Here we demonstrate for the first time that Zn2+ is released into the extracellular space during excitation of hippocampal slices.
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PMID:Release of endogenous Zn2+ from brain tissue during activity. 671 66

The L-isomer of 4-amino-3- isoxazolidinone (L-cycloserine), a potent transaminase inhibitor, was tested for its anticonvulsant action. Intraperitoneal injection of 25 mg kg-1 protects the inbred epileptic mouse (DBA/2J) from convulsions. The drug exerts its protective influence 3 h after administration, and its effect subsides gradually thereafter. A normal mouse (CBA/Ca) can be made prone to sound-induced epilepsy by enhancing its cerebral concentrations of Zn2+ and pyridoxal-5'-phosphate (PLP). Prior administration of 25-50 mg kg-1 L-cycloserine counteracts the convulsive effects of these substances. The pretreated animal is resistant to seizures. The concentrations of glutamate and aspartate in the inferior colliculus of the treated animal are diminished, whereas the concentration of gamma-aminobutyrate is enhanced. The time course of the changes in the amino acid concentrations broadly mirrors the changes in seizure susceptibility following the treatment. Proton nuclear magnetic resonance spectra of a mixture containing equimolar concentrations of L-cycloserine, PLP, and ZnSO4 were obtained. From the resonance peaks of such an adduct, we have ascertained that a molecule of L-cycloserine forms an irreversible Schiff base with the 4-aldehyde group of PLP, and this adduct is stabilized by a zinc ion. The significance of this finding for the anticonvulsant action of the drug is discussed.
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PMID:L-cycloserine: a potent anticonvulsant. 672 95

Seizures produced by intracerebral injection of zinc sulfate in rabbits are a new chronic model of experimental epilepsy. The main features of this model are: the animals are easily controlled, the electrocorticogram is conveniently recorded, the endpoints are definite, and the rate of seizure is higher than with other methods. The commonly used antiepileptic drugs, such as phenobarbital (30 mg/kg), diphenylhydantoin (30 mg/kg), nitrazepam (3 mg/kg), and sodium valproate (300 mg/kg), have therapeutic effects in treating this experimental epilepsy, when they are given intravenously. But they can not protect the rabbits from death, except phenobarbital.
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PMID:Zinc-induced seizures: a new experimental model of epilepsy. 683 78

The effects of hypoglycemia on cerebrovascular permeability to a protein, horseradish peroxidase (HRP), were studied in mice given 3 or 8 units of crytalline zinc insulin intraperitoneally. HRP (10 mg in 0.1 ml saline) was injected intravenously 15 to 20 minutes prior to sacrifice. Both mildly and severely hypoglycemic groups of mice showed a drastic reduction in the normal transit of HRP across cerebral arterioles. The number of normally-stained vessel segments and of HRP-filled endothelial vesicles decreased in insulin-treated mice. In the brains of severely hypoglycemic mice, however, increased parenchymal HRP accumulation occurred. A ruptured blood vessel was found in the center of one-fourth of the focal exudates examined. Electron microscopic examination revealed thrombin, sometimes extending through the vessel wall, and hemorrhage, yet inter-endothelial tight junctions remained intact. Seizures were associated with severe hypoglycemia in 6 out of 10 mice with serum glucose levels below 40 mg/100 ml following 8 units of insulin, but the number of focal exudates per brain was similar in all 10 mice. We conclude that insulin-induced hypoglycemia is associated with decreased HRP transit across cerebral arterioles, and that severe insulin shock is also accompanied by actual rupture of vessel walls and extravasation of blood and HRP into the parenchyma of the brain.
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PMID:Effects of insulin-induced hypoglycemia on cerebrovascular permeability to horseradish peroxidase. 698 50

The effect of phenytoin (PHT) on the metabolism of zinc (Zn) and copper (Cu) has been studied during treatment for epilepsy. Eleven previously untreated epileptics were followed from the start of therapy together with 20 patients on long-term therapy. In eight untreated epileptic males low serum concentrations of Zn (S-Zn) were found. At the start of therapy increased S-Zn and S-Cu concentrations were noted. After 1 month of therapy S-Zn was at pretherapy levels but S-Cu was still increased. No changes in the urinary excretion of the metals or in the CSF-Zn concentrations were registered. In the patients on long-term therapy S-Zn was unchanged while S-Cu and S-ceruloplasmin were increased significantly compared with age- and sex-matched controls. It is postulated that the drug may cause a relative zinc deficiency through a chelate binding between Zn and PHT and/or an increased absorption and accumulation of Cu. These effects may be of importance in the development of intoxication symptoms and may also influence the effectiveness of seizure control.
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PMID:Zinc and copper metabolism in phenytoin therapy. 714 Jun 61

The intracerebroventricular administration of Zn2+ (0.3 mumol/10 microliters) causes epileptic seizures characterized by running fits, jumping, vocalization, fasiculation of facial muscles, myoclonic movements of the limbs and tonic-clonic convulsions. These episodes are blocked or reversed by gamma-aminobutyric acid (0.4 mumol/10 microliters). When assayed under conditions where pyridoxal phosphate was not added, the activity of glutamic acid decarboxylase decreased significantly in hippocampus from 18.9 to 15.3 and 9.7 mumols 14CO2 formed/gram proteins/20 min, 15 and 30 min following administration of Zn2+. The inhibition of glutamic acid decarboxylase by Zn2+ was selective occurring only in hippocampus and not in the hypothalamus, amygdala, caudate or thalamus. The inhibition of glutamic acid decarboxylase was not due to a reduction in the concentration of endogenous pyridoxal phosphate which remained unaltered in hippocampus following Zn2+ administration.
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PMID:The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures. 715 79


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