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

The high seizure susceptibility in epileptic fowl is due to an autosomal recessive mutation. Cyclic AMP and cyclic GMP concentrations were determined in brains from two day old epileptic chicks (homozygotes) during an inter-ictal period as well as during and following a seizure evoked by stroboscopic stimulation. The data were compared to values obtained from non-epileptic carrier chicks (heterozygotes) sacrificed in an unstimulated state or subjected to the seizure evoking stimulus. During the inter-ictal state in epileptics no abnormalities were found in cyclic nucleotide concentrations indicating that the high seizure susceptibility is not related to abnormalities of these nucleotides. Although seizure activity in epileptics was associated with reduced cyclic AMP in the optic lobes this also occurred in carrier chicks subjected to the seizure evoking stimulus. The only significant changes in cyclic GMP levels, occurring as a result of seizures in epileptics, were an increase in cyclic GMP in the cerebral hemispheres during the seizure and a decrease in the optic lobes during the postictal period.
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PMID:Cyclic nucleotides and seizures in a hereditary model of epilepsy. 632 61

Although fatigue is a well-known phenomenon and the phrase "exercised until exhaustion" is commonly understood, there is no unequivocal agreement on the fundamental nature of the fatigue process. Ammonia was linked to the development of fatigue as early as 1922, when ammonia production was observed from stimulated nerve and the question whether there could be a relationship between ammonia production and the muscle activity was raised. The immediate source of ammonia from muscle appears to be a result of the deamination of AMP and is more apparent in fast-twitch than in slow-twitch fibers. More recently, increases in blood ammonia levels have been reported in rats after swimming and in humans after arm work, maximal cycle ergometry, and treadmill exercise. Elevated blood ammonia has also been linked to a surprising variety of functional and metabolic neurological disturbances other than exercise and fatigue, including the development of hepatic coma, convulsions from ammonia toxicity precipitated by high-pressure oxygen breathing, epileptic seizures, and decreased neuronal excitability. In addition, a number of genetic disorders (inborn errors in metabolism, or IEMs) are characterized by elevated blood ammonia concentrations. Symptoms of neural disability in all of the above conditions have been related to the concentration of ammonia in blood. Although these studies do not relate to exercise or fatigue directly, it is conceivable that our understanding of the effect of high concentrations of blood ammonia in these clinical conditions may provide valuable insight into the effect of ammonia during exercise. This paper reviews the effect of ammonia production during exercise and other conditions upon purposeful activity and the development of fatigued states.
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PMID:Ammonia metabolism in exercise and fatigue: a review. 634 52

Sustained epileptic seizures were induced in cats by means of penicillin (PCN). After a three hour period tissue from the archicortex was removed, frozen, and extracted for metabolic studies. The concentration of ATP, ADP, AMP, phosphocreatine, glucose, glucose-6-phosphate, pyruvate, lactate, glutamate and aspartate were determined. There was a 50% decrease in phosphocreatine concentration, a slight decrease in the level of ATP and a slight increase in the levels of ADP and AMP. There was a decrease in the total adenine nucleotide and the ATP/ADP and ATP/AMP ratios. The absence of a significant change in adenylate energy charge potential reflects the remarkable ability of the brain to stabilize its energy state even after intense seizure activity. A reflection of increased glycolysis is the presence of decreased glucose (nearly 50%), and increased lactate, concentrations. The metabolic changes observed in the archicortex are comparable to those observed by others in the neocortex, indicating perhaps the relative metabolic uniformity of these two types of cortex.
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PMID:Metabolic changes in the hippocampus after prolonged epileptic discharge. 661 55

Rats were kindled during exposure to caffeine (50 mg/kg) or saline given IP twenty minutes before daily electrical stimulation of the amygdala until 3 kindled amygdaloid seizures (KAS) occurred. They were then stimulated for 3 days without drug pretreatment followed by 5 additional days with drug pretreatment. There were no significant differences between the two groups in the number of daily stimulations or in the total seconds of cumulative afterdischarge (AD) needed to reach the first KAS. During kindling, the daily average AD tended to be longer in the caffeine treated group. This difference became significant (greater than 200% saline) when the KAS was reached. When KAS animals were stimulated without caffeine pretreatment, the average AD returned to control lengths. When put back on caffeine pretreatment, the average AD was again increased. Caffeine (6-50 mg/kg, IP) was also evaluated in previously kindled rats using suprathreshold (400 mu AMP) and threshold (20 microA increments) seizures. Caffeine had no consistent effect on threshold values. However, 12-50 mg/kg of caffeine increased seizure severity and AD durations after threshold stimulation. With suprathreshold stimulation, the length of the AD was significantly increased only after the highest dose of caffeine. It would appear that caffeine lengthens induced afterdischarges both during the acquisition phase of kindling and in the fully kindled subject. Caffeine does not appear to lower seizure thresholds or increase the rate of acquisition of the KAS in the doses tested in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Caffeine modification of kindled amygdaloid seizures. 663 84

We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2 > 200 mm Hg; group II PaO2 = 50 mm Hg; and group III: PaO2 = 100 mm Hg. We treated a fourth group whose PaO2 = 100 mm Hg with phentolamine to block the 44% rise in blood pressure which occurred with the onset of seizures. PaCO2 was maintained between 30 anf 40 mm Hg in all groups. Brain tissue was sampled rapidly after 0, 10, 20, 30, 60, and 120 seconds of seizures by the freeze-blow technique. With normoxia (PaO2 = 100 mm Hg) or hyperoxia (PaO2 > 200 mm Hg), adenosine increased within ten seconds of the onset of seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A reduction in PaO2 (50 mm Hg) or systemic blood pressure during seizures caused a further augmentation in the increase in brain adenosine levels. During the seizure period, transient changes in adenine nucleotides and energy charge were observed, but PCr remained depressed and lactate continued to rise. The rapid and sustained increase in cerebral adenosine levels, temporally paralleling the changes in cerebral blood flow, supports the role for adenosine in the regulation of cerebral blood flow.
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PMID:Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure. 677 98

The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two "vulnerable" structures (cerebral cortex and hippocampus) and the "resistant" one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.
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PMID:Metabolic changes in cerebral cortex, hippocampus, and cerebellum during sustained bicuculline-induced seizures. 729 97

Previously, we have shown a significant increase in number of GABAB receptor binding sites in neocortex and thalamus of lethargic (lh/lh) mice, a mutant strain exhibiting absence seizures. This study was performed to test our hypothesis that presynaptic GABAB receptors would inhibit [3H]GABA release to a greater degree in lh/lh mice compared with their nonepileptic littermates (designated +/+). Synaptosomes isolated from neocortex and thalamus of age-matched male lh/lh and +/+ mice were similar in uptake of [3H]GABA. In the neocortical preparation, baclofen dose-dependently inhibited [3H]GABA release evoked by 12 mM KCl, an effect mediated by GABAB receptors. The maximal inhibition (Imax) value was significantly greater (80%) in lh/lh than +/+ mice, whereas the IC50 (3 microM) was unchanged. In the thalamic preparation, the effect of baclofen (50 microM) was 58% less robust in lh/lh mice. Other effects mediated by GABAB receptors (inhibitions in Ca2+ uptake and cyclic AMP formation) were also significantly reduced in thalamic synaptosomes from lh/lh mice. These data suggest a greater presynaptic GABAB receptor-mediated effect in neocortex and a reduced effect in thalamic nuclei of lh/lh mice. It is possible that selective effects of presynaptic GABAB receptors or GABA release in neocortex and thalamic nuclei of lh/lh mice may contribute to mechanisms underlying absence seizures.
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PMID:GABAB receptor-mediated effects in synaptosomes of lethargic (lh/lh) mice. 759 94

Adenosine monophosphate, inosine monophosphate, inosine, adenosine, guanosine, adenine, guanine, hypoxanthine, xanthine, uric acid, and pyrimidines bases were determined in cerebrospinal fluid (CSF) of 52 children after simple febrile seizures and in a control group of 63 children. There was no statistically significant difference between the two groups for any of these metabolites, suggesting that simple febrile seizures (SFS) neither significantly disturb the metabolism of nucleotides, nucleosides, or bases nor significantly deplete neuron adenosine ATP levels. Therefore, they do not appear to constitute a threat of neuronal damage.
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PMID:Cerebrospinal fluid purine metabolites and pyrimidine bases after brief febrile convulsions. 761 24

We report three neonates with transient hypoparathyroidism with elevated parathyroid hormone (PTH) levels to clarify further the pathogenesis of late neonatal hypocalcemia and calcium homeostasis. Clinical signs were seizures starting at age of 10 and 11 days. The biochemical features were characterized by transient hypocalcemia and hyperphosphatemia due to a high transport maximum of the phosphate/glomerular filtration rate, despite high PTH levels. All had normal magnesium and calcidiol levels (at least 5 micrograms/l) for their age, and this precludes hypoparathyroidism due to low magnesium levels and hyperparathyroidism due to overt vitamin D deficiency. To diagnose pseudohypoparathyroidism type I, intravenous human PTH (1-34) infusions were performed; however, they showed brisk responses of plasma and/or urine cyclic AMP in response to the PTH infusion, but the phosphaturic response to the PTH was sluggish compared to the controls. All three showed an increase in serum alkaline phosphatase activity, suggesting PTH stimulation of osteoblasts. They were treated initially with calcium lactate or (1 alpha)-hydroxycalciol/calcitriol. Their hypoparathyroid condition, however, was transient; they maintained normal serum calcium and PTH levels without medication before the age of 6 months. The etiology, possibly intracellular signal transduction distal to cyclic AMP and/or distinct from adenylate cyclase in the kidney, is developmental and the condition was resolved completely within 6 months of age. We have termed this condition "transient pseudohypoparathyroidism of the neonate".
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PMID:Transient pseudohypoparathyroidism of the neonate. 765 38

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.
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PMID:Protection of the brain by carnitine. 774 96


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