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)

Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate peroxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving gamma-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment.
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PMID:Post-traumatic epilepsy: cellular mechanisms and implications for treatment. 222 73

The behavioral changes and histological damage to the brain of rats were examined following lesions of the midlateral posterior hypothalamic area (MLPHA) made by passing electrical current through a metal electrode or through a glass pipette containing hydrogen ion (HCl) or kainic acid. Control experiments included placement of pipettes containing saline and imposing the same current as used in kainic-acid-containing electrodes (sham). Subcutaneous injections of kainic acid assessed damage that may be attributed to general neuronal cytotoxicity or limbic seizures. The effect of diazepam on alleviating behavioral changes and structural damage in kainic-acid-injected rats was examined. The current used to inject kainic acid produced significant damage to both neurons and axons of passage at the injection site. Degeneration of nerve terminals following kainic acid injections in the MLPHA was widespread, not predictably reduced by diazepam premedication and differed in only minor details from degeneration induced by subcutaneous injections.
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PMID:An appraisal of some lesioning methods applied to the posterior hypothalamus in rats. 259 Aug 31

Fatal or near-fatal hydrogen peroxide ingestions are rarely encountered. We report the case of a 33-year-old woman who experienced seizure activity, respiratory arrest, and residual neurologic deficits after accidentally ingesting industrial-strength 35% hydrogen peroxide.
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PMID:Near-fatal hydrogen peroxide ingestion. 273 99

An experimental limbic seizure was induced in cats by microinjection of kainic acid into the left amygdala. Measurement of regional cerebral blood flow (rCBF) in the limbic structure and cerebral cortex was performed by means of the hydrogen clearance method. Immediately after the development of continuous multiple spikes, rCBF increased about 2-fold in the left amygdala (LA) and remained so during the seizure. When continuous multiple spikes were transmitted to the left hippocampus (LH), rCBF in the LH increased to 140% of the baseline value, but in the right amygdala (RA) and left sensorimotor cortex (LCx) it remained unchanged. During limbic seizure in which spike discharges propagated to the LCx, rCBF in the LA, RA, LCx and LH increased to 220%, 130%, 120% and 190%, respectively. In the interictal stage in which interictal spike discharges intermittently appeared in the LA, rCBF returned to baseline values in the primary and secondary foci. The results show that rCBF increased almost simultaneously with the development of the seizure in the primary focus and the areas where seizure propagation were observed, and returned to baseline value once the seizure had disappeared. During the interictal stage, rCBF in the primary focus was only slightly increased in spite of persistence of interictal spike discharges.
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PMID:Regional cerebral blood flow and kainic acid-induced focal limbic seizures in cats. 319 95

Regional cerebral blood flow (rCBF) was studied by means of electrolytic hydrogen clearance method in chronically prepared adult cats during development of limbic seizures induced by KA microinjection into the unilateral amygdala. Stereotaxic operation was carried out on 7 adult cats. Bipolar electrodes were placed in the lateral nuclei of bilateral amygdala (LA: left amygdala, RA: right amygdala), and in the ipsilateral dorsal hippocampus (LH). Teflon needles with inner stainless steel needle guides were placed in LA, RA, LH and left anterior sigmoid gyrus (LCx) so as to introduce platinum electrodes for rCBF measurements. The teflon needle placed in LA was also utilized for KA microinjection (1 microgram). Measurements of rCBF were done before (control) and after KA microinjection. Control rCBF were as follows; LA: 41.6 15.9, RA: 40.7 12.2, LH: 39.1 10.9, LCx: 55.4 20.7 (ml/100 g/min). After KA microinjection, measurements of rCBF were made during limbic seizure stage (LSS) and transfer stage (TS). TS was divided into two stages; early TS and late TS. In LSS, 50 to 92% increase of rCBF were noted as follows; LA: 79.7 23.7, RA: 66.1 18.1, RH: 58.6 17.6, LCx: 91.4 17.8 (ml/100 g/min). In early TS, rCBF in all recorded sites returned to the same level as control rCBF. In late TS, rCBF in LA and LH were slightly lower than the level of control rCBF. Pathological examination of LA and LH in early and late TS showed different features. In late TS, astrocytic proliferation was remarkable while it was mild in early TS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regional cerebral blood flow during development of limbic seizures induced by kainic acid (KA) microinjection into unilateral amygdala in chronic cats]. 324 90

The relative ability of the enantiomers of the ethyl and m-nitrophenyl esters of nipecotic acid to block convulsions induced by bicuculline and pentylenetetrazol, as well as to block the uptake of GABA into whole brain mini-slices, was studied in mice. Neither (+)ethyl nipecotate hydrogen tartrate [(+)E.Tartrate], which is hydrolyzed to (-)nipecotic acid, nor (-)ethyl nipecotate hydrogen tartrate [(-)E.Tartrate], which is hydrolyzed to (+)nipecotic acid, provided protection against challenge with bicuculline. Both (+)E.Tartrate and (-)ethyl nipecotate hydrochloride [(-)E.HCl], which are hydrolyzed to (-)nipecotic acid, blocked seizures induced by pentylenetetrazol. However, neither (-)E.Tartrate nor (+)ethyl nipecotate hydrochloride [(+)E.HCl], which are hydrolyzed to (+)nipecotic acid, provided significant protection against challenge with pentylenetetrazol. These results agree with the relative ability of these compounds to inhibit the uptake of GABA, where (-)nipecotic acid was more potent than (+)nipecotic acid and (+)E.Tartrate was more potent than (-)E.Tartrate. The enantiomers of m-nitrophenyl-3-piperidinecarboxylate hydrochloride, (+)MNPC.HCl and (-)MNPC.HCl, were almost equi-effective in preventing seizures induced by bicuculline. This lack of significant difference in anticonvulsant activity is in contrast with the ability to inhibit the uptake of GABA, where (-)MNPC.HCl was significantly more potent than (+)MNPC.HCl. Changing the route of administration from subcutaneous to intraperitoneal injection reduced the onset of time of the peak effect and the anticonvulsant potency of (+/-)MNPC.HCl. Cholinergic effects were observed with the administration of (+)E.Tartrate and (-)E.HCl, but not with (-)E.Tartrate, (+)E.HCl, (+)MNPC.HCl or (-)MNPC.HCl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of prodrug esters of nipecotic acid. 339 69

Modeling studies revealed that progesterone, testosterone, and estradiol are stereochemically complementary to the cavity formed between base pairs in the DNA sequence, 5'-dTdG-3' X 5'-dCdA-3'. Each steroid aligned precisely with the topography of the cavity and formed 2 stereospecific hydrogen bonds linking phosphate oxygens on adjacent DNA strands. Hydrogen bonding donor-acceptor relationships were different for each hormone. The remarkable stereochemical specificity of the hormone-DNA complexes was demonstrated by the lack of complementarity of steroid enantiomers and steroid analogs having alternate ring systems and/or changes in the position of functional groups. Fit of molecules into DNA in the manner of the parent hormone correlated with biological activity. Antagonists also fit into the cavity but differed from agonists in their hydrogen bonding linkages to DNA and/or extended out of the cavity beyond the helix. Unlike flat intercalating agents which form stable complexes with DNA, wedge shaped steroids may thus be capable of forming reversible sequence-specific complexes with DNA. We conclude that the stereochemistry of DNA can be used to predict hormonal activity.
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PMID:The stereochemical complementarity of DNA and reproductive steroid hormones correlates with biological activity. 375 4

This article reviews normal acid-base regulation, related laboratory tests, and the potential disorders if the body's ability to compensate is disrupted. Acid derived from the oxidation of proteins and through tissue metabolism must be excreted or neutralized daily by the kidneys and lungs to maintain a proper acid-base balance. Acid-base homeostasis is normally maintained by chemical buffering, changes in renal hydrogen-ion excretion, and alterations in the rate and volume of alveolar ventilation. Metabolic disorders are characterized by disturbances in bicarbonate (HCO3-) concentration, and respiratory disorders develop with primary alterations in the partial pressure of carbon dioxide (Pco2). Metabolic acidosis is characterized by low pH, low serum HCO3- concentrations, and a compensatory decrease in Pco2 with hyperventilation. Bicarbonate administration can correct this disorder, and equations for calculating the necessary amount of HCO3- are presented. Metabolic alkalosis is characterized by a primary increase in HCO3-, compensatory hypoventilation, and an increase in Pco2 (hypercapnia). The drug therapy for this disorder is directed at either saline-responsive alkalosis or saline-resistant alkalosis. Formulas for estimating the volume requirements of patients and appropriate doses of acidifying agents are presented. Respiratory acidosis and alkalosis are also discussed. The initial therapy for the hypercapnia associated with respiratory acidosis requires reversing the underlying pulmonary disease with steroids, bronchodilators, or antibiotics. The increased Pco2 in this conditions must be lowered slowly to avoid precipitating cardiac arrhythmias and seizures. The correction of respiratory alkalosis requires elevating the Pco2 and again treating the underlying disease. Pharmacists should be knowledgeable about acid-base regulation and the disorders that frequently occur with disease because drugs are capable of inducing or exacerbating these disorders and are often key elements in therapy.
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PMID:Simple acid-base disorders. 393 55

Patients with arteriovenous malformations of the brain, who are subject to disabling or fatal recurrent hemorrhage, seizures, severe headache, and progressive neurologic deficits, may be considered unsuitable for conventional therapies (craniotomy with excision or embolization), usually because of the location, size, or operative risk of the lesion. We have treated such patients with stereotactic Bragg-peak proton-beam therapy and report the follow-up of 74 of the first 75, 2 to 16 years after treatment. Proton-beam therapy is intended to induce subendothelial deposition of collagen and hyaline substance, which narrows the lumens of small vessels and thickens the walls of the malformation during the first 12 to 24 months after the procedure. Two deaths from hemorrhage occurred in the first 12 months after treatment, but no lethal or disabling hemorrhages occurred after this interval. Seizures, headaches, and progressive neurologic deficits were in most cases arrested or improved. Bragg-peak proton-beam therapy appears to be a useful technique for treatment of intracranial arteriovenous malformations, especially those that are unsuitable for treatment by other methods.
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PMID:Bragg-peak proton-beam therapy for arteriovenous malformations of the brain. 630 63

The relationship between neuronal epileptic activity and regional cerebral blood flow was studied by means of hydrogen clearance method (rCBF). Measurements of rCBF in the limbic structure and cerebral cortex were performed during limbic seizures induced by a microinjection of kainic acid to the left amygdala under concurrent monitoring of polygraph. Pentobarbital (35 mg/kg, i.p.) anesthesia was induced and cats were artificially ventilated. Physiological parameters such as blood pressure, body temperature, PaO2, PaCO2 and HCO3 were kept stable. After fixation of the cat's head in a stereotaxic device, stainless screw electrodes were placed over bilateral anterior sigmoid gyrus so as to touch the dura mater for cortical EEG monitoring. Bipolar needle electrodes were stereotaxically placed to both amygdala and the left dorsal hippocampus. Platinum electrodes were stereotaxically placed to the left amygdala, dorsal hippocampus and sensorimotor cortex. After measurements of control rCBF, a microsyringe was stereotaxically inserted into the left amygdala and kainic acid solution (2 micrograms) was injected. Polygraphic monitoring followed. Five to 30 minuted after kainic acid injection, continuous multiple spikes appeared in the left amygdala. Forty to 120 minutes later, continuous multiple spikes transmitted to the left hippocampus. Two to five hours later, limbic seizure occurred. The limbic seizure lasted five to eight hours and interictal discharges appeared. Repeated measurements of rCBF were done. In the left amygdala, rCBF increased about two-fold of the control immediately after development of continuous multiple spikes and remained increased as long as the seizure persisted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regional cerebral blood flow in limbic seizures induced by microinjection of kainic acid into amygdala in cats]. 648 36


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