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)

Intracerebroventricular administration of 10--20 microgram of steroid-O-sulfates induced hypermotility, agitation, salivation, EEG abnormalities, stereotypies, wet dog shakes and seizures. Equivalent effects resulted from 30--200 microgram morphine sulfate (H2SO4 salt), 50 microgram EGTA or 300--400 microgram of sodium sulfate or phosphate, but not chloride, nitrate or acetate. Non-steroid sulfates, steroid glucuronides and steroid phosphates were inactive. Naloxone, previously found to antagonize the excitatory effects of androsterone sulfate, failed to antagonize those of cortisol sulfate, sodium sulfate or EGTA. These findings suggest a role for extracellular calcium ions and for sulfate derived from circulating steroids in central responses to opiates.
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PMID:Opiate-like excitatory effects of steroid sulfates and calcium-complexing agents given cerebroventricularly. 21 60

The present study was designed to provide information on the effects of lead, mercury, and nickel on lethality, body weight, and brain excitability in the adult rat. Both short- (2 days) and long-term (6 wk) drug administrations were carried out in adult male albino rats (Sprague-Dawley, Zivic-Miller). Based on the mg/kg/day of drug given over a 2-day period, the LD50 values were as follows: Pb(Ac)2, 215; Pb(NO3)2, 65.9; MMC, 11.9; HgCl2, 4.5; Ni(Ac)2, 35-40; NiSO4, 35-40. High doses of each of the metals administered acutely caused a drop in body weight but had an inconsistent effect on flurothyl-induced seizure thresholds. Pb(Ac)2, 200 mg/kg/day for 2 days, produced a statistically significant anticonvulsant effect, while 50 mg/kg Pb(NO3)2 resulted in a fall in threshold. Both NiSO4 and Ni(Ac)2, 30 mg/kg, increased seizure threshold. Neither the organic nor inorganic mercury altered thresholds. Long-term administration of Pb(Ac)2, MMC, or HgCl2 resulted in marked effects on body weight but no significant change in brain excitability.
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PMID:Toxicity to heavy metals and relationship to seizure thresholds. 91 36

Glycerol acute renal failure (ARF) was examined to see if it alters theophylline (Th) neurotoxicity in rats. Concentrations of Th in serum, cerebrospinal fluid and in brain at seizure onset were similar in control and ARF rats infused with Th. Thus, glycerol ARF fails to alter Th neurotoxicity, an effect similar to that noted previously with uranyl nitrate but not with ureter ligation.
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PMID:Theophylline neurotoxicity is unaffected by glycerol-induced renal failure. 208 97

The purpose of this investigation was to determine if the pharmacodynamics of the central nervous system stimulant pentylenetetrazol (PTZ) are altered in renal dysfunction. Female rats subjected to bilateral ureteral ligation (with sham-operated controls) or injected with uranyl nitrate (with saline injected controls) were infused intravenously with PTZ until the onset of either a minimal (myoclonic jerk) or maximal (tonic hindlimb extension) seizure. Neither chemically nor surgically induced renal dysfunction caused a change in the concentrations of PTZ in CSF, serum, or brain at onset of minimal seizures. When PTZ was infused to onset of maximal seizures, the rats with chemically induced renal dysfunction required higher concentrations, whereas the ureter-ligated rats convulsed at lower concentrations of PTZ than did the corresponding control animals. Thus, the effects of experimental renal dysfunction on the convulsant action of PTZ are dependent on both the disease model and the endpoint used for the pharmacodynamic measurement. Apparently, renal dysfunction did not affect the PTZ-induced seizure threshold, but inhibited the spread of seizures. The increased sensitivity of ureter-ligated rats may be due to their pronounced retention of water, since water loading is known to increase seizure susceptibility.
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PMID:Kinetics of drug action in disease states. XXXIII: Disparate effects of pentylenetetrazol in rats as a function of renal disease model and pharmacologic endpoint. 271 36

Agarose isoelectric focusing, followed by protein transfer to cellulose nitrate membrane and double-antibody avidin-biotin peroxidase staining (avidin-biotin agarose isoelectric focusing), was used to demonstrate oligoclonal IgG bands in unconcentrated cerebrospinal fluid (CSF) and serum; 161 consecutive pediatric patients, ages 6 months to 16 years with a variety of mainly neurologic disorders, were studied. The procedure was standardized for agarose isoelectric focusing (AIF) using 5 microliter specimens containing 125 ng of IgG. Oligoclonal bands were found in the CSF of 12% of the patients; bands were found simultaneously in the CSF and serum of 10% of the patients, mostly those with nervous system infections, but also those with central nervous system tumors, seizures, or migraine. In about 50% of positive cases, oligoclonal bands constituted the only CSF abnormality, reflecting an abnormal humoral immune response within the CSF-central nervous system compartment. Avidin-biotin AIF can be recommended as an integrated part of routine CSF examinations in children.
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PMID:Demonstration in children of oligoclonal IgG bands in unconcentrated CSF using agarose isoelectric focusing and immunolabeling. 333 4

Theophylline, the bronchodilating agent, can cause life-threatening, generalized seizures when plasma concentrations exceed the usual therapeutic concentration range. However, the plasma concentrations of theophylline associated with this neurotoxic effect vary widely between patients. To determine the reasons for the wide variation, and thereby to facilitate prevention or early treatment of theophylline-induced neurotoxicity, an animal model of theophylline-induced seizures was developed and has now been used to determine the effect of experimental renal failure on the concentrations of theophylline that cause convulsions. Adult female rats were subjected to bilateral ureteral ligation or injected with uranyl nitrate to produce renal failure or dysfunction. Sham-operated and saline-injected rats, respectively, served as controls. Theophylline was infused i.v. at either 1.03 or 2.06 mg/min until the onset of maximal seizures. Renal failure due to ureter ligation was associated with a substantial reduction of the dose of drug required to produce seizures, the concentrations of total and free (unbound) theophylline in serum and the concentrations of theophylline in the brain and cerebrospinal fluid at onset of seizures. The concentrations of theophylline metabolites were very low and did not account for the enhanced neurotoxicity. No apparent change in the neurotoxicity of theophylline was observed in rats with uranyl nitrate-induced renal dysfunction. The results of the investigation on ureter-ligated rats are consistent with recent clinical findings of a higher incidence of theophylline-induced neurotoxicity in azotemic patients. The experimental methodology may therefore be suitable for the prospective identification of other potential clinical risk factors for theophylline neurotoxicity.
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PMID:Kinetics of drug action in disease states. XVIII. Effect of experimental renal failure on the pharmacodynamics of theophylline-induced seizures in rats. 380 13

Treatment of ischemic deficits caused by vasospasm relies on enhancing cardiac output, inducing arterial hypertension, and expanding the intravascular volume in an attempt to improve CBF. Different treatment protocols exist from institution to institution to achieve these goals. The role of calcium-channel blockers now is well established. The newest focus on prevention of vasospasm includes tPA and a variety of anti-inflammatory drugs and potential neuroprotective drugs under research. Endovascular therapy for vasospasm has an increasing role in treating patients who are unable to tolerate induced hypertension or aggressive volume augmentation. We will return to our index case of the 63-year-old woman with SAH caused by an ACoA aneurysm to review some major management issues. After placing a ventriculostomy and slowly lowering ICP, the patient became alert and was fully oriented. She had aneurysm surgery on hospital day 2, with an uncomplicated immediate postoperative course. A Swan-Ganz catheter, placed for intraoperative monitoring, was kept in place and she was hydrated with 125 mL/hour of normal saline, achieving a PAWP of 10 to 16 mm Hg. Her mean arterial blood pressure without pharmacologic intervention was 95 to 110 mm Hg. She had continued clinical improvement with resolution of her left hemiparesis. On hospital day 5, her ventriculostomy was clamped because cerebrospinal fluid drainage was minimal. The following morning, the patient was arousable only to deep pain and her left side was flaccid. An emergent CT scan demonstrated no new hemorrhage, no increase in ventricular size, and no infarct. Vasospasm was considered the most likely cause. Hypertensive therapy was about to be initiated with a phenylephrine drip, but within an hour she was fully alert and moving all extremities equally. A search for other potential causes of neurologic decline was undertaken and revealed a phenytoin level of 5.5. It was thought that the patient most likely had had a seizure and that her clinical deterioration represented a postictal state. She received a bolus infusion of phenytoin. On hospital day 7, the patient became confused, insisting that her nurse was her son and ordering him out of her "apartment." Lower extremity weakness was detected. CT scan was unchanged. Phenylephrine was started but she developed precordial lead ST elevation and elevated cardiac enzymes. Topical nitrate therapy was initiated and phenylephrine was discontinued. The patient underwent emergent cerebral angiography, which demonstrated moderate to severe bilateral ACA spasm and moderate right MCA spasm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of aneurysmal subarachnoid hemorrhage. 747 15

Cellular volume and potassium contents were determined in rat astrocytes from primary culture following suspension in isoosmotic (269 mOsm) and hypoosmotic (136 mOsm) phosphate-buffered saline (PBS) containing various potassium concentrations. Within 1 min of suspension in hypoosmotic PBS, cells swelled to 135% of their volume in isoosmotic PBS. This initial swelling was not altered by varying the potassium concentration of the hypoosmotic PBS. After suspension in hypoosmotic PBS containing 3.2 mM potassium, a regulatory volume decrease (RVD) was observed. Higher concentrations of potassium in hypoosmotic PBS inhibited RVD following osmotic swelling. Cells swollen in hypoosmotic PBS containing 50 mM potassium continued to swell for 7 min, reaching a volume of 141% of their initial isoosmotic volume. After 7 min, these cells demonstrated a subsequent decrease in volume. The swelling observed between 1-7 min after suspension in hypoosmotic PBS containing 50 mM potassium was not affected by 10 microM gadolinium, 1 mM quinine, 1 mM DIDS (4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM SITS (4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM furosemide, or 100 microM bumetanide. Normal RVD was obtained in hypoosmotic PBS containing 50 mM potassium, if chloride was replaced with gluconate (but not nitrate) to reduce the extracellular K.Cl product to that of hypoosmotic PBS containing 3.2 mM potassium. The volume decrease seen between 7-30 min after exposure to hypoosmotic PBS containing 50 mM potassium was blocked by 1 mM DIDS, 1 mM SITS, or 1 mM furosemide. Cellular potassium content was elevated by approximately 60% after 7 min exposure to isoosmotic or hypoosmotic PBS containing 50 mM potassium. In hypoosmotic PBS, this increase in cellular potassium was reduced with replacement of chloride by gluconate, but not by nitrate. The results indicate that astrocytes swollen in PBS containing elevated potassium concentrations continue to swell, in part, by accumulation of potassium plus chloride mediated by an approach to Donnan equilibrium. Cotransport carriers or stretch-activated channels do not play a role in the enhanced swelling observed in hypoosmotic PBS containing 50 mM potassium. We suggest that a voltage-sensitive chloride channel mediates this continuation of cell swelling. This mechanism may be important in the persistent swelling of astrocytes observed in pathologic conditions such as trauma and seizures where extracellular potassium is elevated, or when other factors are present which may cause astroglial depolarization.
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PMID:Hypoosmotic volume regulation of astrocytes in elevated extracellular potassium. 774 27

The purpose of this investigation was to compare the efficacy of diazepam and a water soluble pro-diazepam drug, avizafone (lysyl, peptido-aminobenzophenone diazepam pro-drug) in preventing or reducing the severity of soman-induced neuropathology in rats and to determine the temporal relationship between seizure initiation, anticonvulsant administration and the incidence and severity of soman-induced neuropathology. Brains from rats, treated with a convulsant dose of soman (pinacolyl methylphosphonofluoridate) and anticonvulsants such as diazepam and avizafone, were evaluated by light microscopy for evidence of neuropathology. All rats received atropine methyl nitrate (20 mg/kg, ip)+the bispyridinium acetylcholinesterase reactivator HI-6 (125 mg/kg, ip; 1-(((4-(aminocarbonyl)pyridinio) methoxy)methyl)-2-((hydroxyimino)methyl)-pyridinium dichloride) in the same solution 10 min before soman (130 micrograms/kg,sc). Three days later the rats were perfused and the tissue fixed for histological evaluation. Necrosis and/or malacia (degenerative changes) and hemorrhage were observed in some groups. The sites where pathology was most frequently observed and with greater severity were the piriform cortex, amygdala and (dorsal) thalamus. Less severe changes were observed in the cerebral cortex and hippocampus. There were no changes in the hypothalamus. Diazepam given 10 minutes before soman prevented the occurrence of soman-induced convulsions and neuropathology (i.e. degenerative changes were not then seen). Diazepam given at the start of the soman-induced convulsions reduced considerably the convulsions and the degree of neuropathology. Avizafone given 10 minutes before soman reduced slightly the effect of soman. Other treatments (diazepam given 30, 60 and 120 minutes after the start of the convulsions and avizafone given at the start of convulsions) showed little or no effect on the neuropathology associated with soman administration. The results of this study have demonstrated that the use of an anticonvulsant, such as diazepam, must be initiated shortly after soman exposure in order for any therapeutic benefit to be realized.
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PMID:Efficacy of diazepam and avizafone against soman-induced neuropathology in brain of rats. 816 92

Temporal changes in kainate-induced seizure activity and hippocampal NO generation were evaluated simultaneously in conscious rats by using in vivo microdialysis and by determining the concentrations of nitrite and nitrate in perfusates. Intraperitoneal injection of kainic acid produced 'wet dog shake', focal seizure of the limbs and neck, hypersalivation, or generalized convulsion. These behavioral changes peaked at 120 min after the drug challenge and lasted for about 100 min. In contrast, the concentrations of NO metabolites, nitrite and nitrate, in the hippocampal perfusates increased rapidly and reached a plateau level at 40 min after the injection, and the level remained high for over 220 min. The increase was more marked in animals presenting severe seizures than those presenting mild ones. Pre-treatment with 25 mg/kg N(G)-nitro-L-arginine methyl ester promoted the severity of kainate-induced seizures, but it suppressed the increase in NO metabolites. These results suggest that kainic acid enhances hippocampal NO generation in a severity-related manner of the induced seizures. The enhanced NO generation upon kainate challenge appears mainly to be involved in seizure suppression.
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PMID:Kainic acid may enhance hippocampal NO generation of awake rats in a seizure stage-related fashion. 987 60


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