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 activity of the free radical scavenger, superoxide dismutase, was studied in focal cerebral ischemia produced in Mongolian gerbils (Meriones unguiculatus) by occluding the right common and left external carotid arteries under halothane anesthesia. After recovery from anesthesia animals were classified according to their neurologic symptoms. Five animals exhibiting neurologic symptoms such as hemiparesis and rolling seizures were reanesthetized 120 min after vascular occlusion and their brains frozen in situ with liquid nitrogen. A series of 20-micron-thick coronal sections was cut in a cryostat; pictorial representations of tissue pH, ATP, and glucose were obtained using fluorescent and bioluminescent techniques. Using a highly sensitive bioluminescent technique, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Mn-superoxide dismutase (Mn-SOD) activities were then measured in samples from both ischemic and nonischemic regions of the remaining tissue block. Cu,Zn-SOD and Mn-SOD activities were, respectively, 13.9 +/- 0.7 X 10(3) units/g and 5.4 +/- 0.3 X 10(3) units/g in the nonischemic tissue, and 13.2 +/- 0.6 X 10(3) units/g and 5.0 +/- 0.2 X 10(3) units/g within the ischemic tissue. Thus focal cerebral ischemia does not lead to a global decrease in SOD activity, as observed by others after heart and liver ischemia.
 ...
PMID:Superoxide dismutase activity in experimental focal cerebral ischemia. 406 77

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.
 ...
PMID:Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase. 423 89

A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.
 ...
PMID:Reduction in caffeine toxicity by acetaminophen. 630 77

Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular lesions. In the present study, the effects of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-2619) on neurological signs, local cerebral blood flow, and cerebral energy metabolism were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery occlusion (BCAO). Pretreatment with CV-2619 (10-100 mg/kg, p.o.) for three or ten successive days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in the SHRSP. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When CV-2619 (100 mg/kg for 3 days) was given orally, it did not inhibit a decrease in regional cerebral blood flow induced by the carotid artery occlusion. However, the same treatment markedly inhibited increases in lactate content and lactate/pyruvate ratio and a decrease in ATP content in the cerebral cortex. In addition, the compound showed no effect on cerebral blood flow in normal rats. These results suggest that CV-2619 has an ameliorating effect on neurological deficits related with cerebral ischemia, and this effect is mediated by improved cerebral energy metabolism.
 ...
PMID:[Effects of idebenone (CV-2619) on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia]. 650 Apr 4

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.
 ...
PMID:Metabolic changes in the hippocampus after prolonged epileptic discharge. 661 55

Incomplete global cerebral ischemia was induced by clamping the bilateral common carotid arteries of spontaneously hypertensive rats (SHR) and blood reperfusion was allowed by declamping the arteries after indicated times. To investigate the possible role of lipid peroxidation which causes irreversible ischemic cell injury during ischemia and subsequent reperfusion, cerebral energy metabolism, brain edema, neurological signs and cerebral and serum lipid peroxides were examined. The effect of alpha-tocopherol administration on these parameters was also studied from the standpoint of its action as a free radical scavenger. During ischemia up to 5 hours, cerebral ATP decreased and lactate increased rapidly, and concomitantly neurological signs, such as eye closure and jumping seizures, and slowly progressing brain edema were observed. The level of lipid peroxides in the brain and serum remained practically unchanged during ischemia, although an increasing tendency was noted. When blood reperfusion was allowed 3 hours after ischemia, tissue ATP level was restored only partially (67.4% of normal), but lactate returned to the normal level. The reperfusion resulted in a rapid rise in the lipid peroxide level both in cerebral tissue and serum and also caused a more severe expression of neurological signs. Intravenous injection of alpha-tocopherol (20 mg/kg body weight) 30 minutes prior to ligation of the carotid arteries significantly suppressed the rise in lipid peroxides both in the brain and serum, improved the severely expressed neurological signs, and promoted resynthesis of ATP. These improvements in the parameters were observed only after the reperfusion was made following ischemia for 3 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of alpha-tocopherol administration. 665 3

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.
 ...
PMID:Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure. 677 98

Audiogenic seizure-prone mice (DBA/2J) were exposed to a broad band noise source. A reproducible response consisting of wild run, clonus, and tonic stages resulted in all mice. Layers 1 and pyramidal from the parietal cortex and the molecular and Purkinje cell-rich layers from the cerebellar vermis were separately analyzed for glucose, glycogen, ATP, and phosphocreatine. Results showed a biphasic cerebellar response, with decreases in high energy phosphates occurring during the wild run and tonic stage. In the cortex, similar changes occurred in the pyramidal cell layer, but the decreases were not as pronounced as those in the cerebellum. Cells from layer 1 of the parietal cortex were not affected as much as those of the pyramidal layer, suggesting a differential effect between neuronal and nonneuronal cell populations. The greater response of the cerebellum could indicate an attempt to reduce the severity of both the wild run and the tonic extension seizure.
 ...
PMID:Audiogenic seizure-induced changes in energy metabolites in cerebral cortical and cerebellar layers. 681

Isoniazid is a useful chemical convulsant in that metabolic events associated with the preseizure state can be easily examined. In the present study, net levels of glucose, glycogen, ATP, and phosphocreatine were measured using enzymatic techniques in control mice, and in those injected with isoniazid. Results from this study showed a differential effect of isoniazid on cells from the cerebral cortex and the cerebellum. In the preseizure stage, the high energy phosphates ATP and phosphocreatine were decreased in layer 1 and the pyramidal cell layer of the cerebral parietal cortex, but were unchanged in the cerebellum. At the onset of seizures, metabolites were decreased not only in cortical layers, but in the molecular layer and Purkinje cell rich layer of the cerebellum as well. The somewhat delayed response of the cerebellum emphasizes the differential nature of metabolism in various brain regions. Such a delay in cerebellar energy response to perturbation may be conducive to the seizure state. In another series of mice, either sodium valproate or clonazepam was administered prior to isoniazid, and metabolite studies repeated. Results showed that at a time when each anticonvulsant acted to eliminate overt seizure activity, the reduction in ATP and phosphocreatine was not as great as it was in seizing mice treated with isoniazid alone.
 ...
PMID:Isoniazid induced seizures and cerebral cortical and cerebellar energy metabolism. 681 36

2'-Deoxycoformycin (dCF), a tight-binding inhibitor of adenosine deaminase, has recently been entered into clinical trials. Toxicity has included lymphopenia, seizures, coma, conjunctivitis, renal failure, and hemolysis. Mice treated with dCF on a variety of schedules exhibited massive hemolysis. Hemolysis was brief, lasting about 20 hours, and did not recur upon readministration of the drug unless readministration was delayed for at least 6 days after initial exposure, which suggests that a sensitive subpopulation of cells was selectively destroyed. Splenectomy failed to protect the animals from dCF-induced hemolysis. Administration of adenosine or 2'-deoxyadenosine without dCF did not cause hemolysis, and use of these two agents with dCF did not potentiate the observed hemolysis. ATP and dATP levels were measured in erythrocytes, and changes in levels of these nucleotides did not correspond with the development of hemolysis.
 ...
PMID:2'-Deoxycoformycin-induced hemolysis in the mouse. 697 51


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>