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)

Cerebrospinal fluid lipoperoxides, measured as the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct, were quantified by adapting the plasma liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to cerebrospinal fluid. Reference values for spinal fluid specimens from 91 adults, ages 17 to 95 y, and 37 children, ages 8 d to 8 y, were determined. Their concentrations were not significantly different (P = 0.222), adults having a mean (and SD) of 0.11 (0.06) mumol and children 0.10 (0.04) mumol of MDA per liter. Their ranges were 0.02-0.26 and 0.04-0.21 mumol of MDA per liter, respectively. We found concentrations in cerebrospinal fluid to be increased in several central nervous system disorders, including seizures, cerebral infarction, alcoholic encephalopathy, and, perhaps, prematurity. The presence of other thiobarbituric acid-reactive substances in cerebrospinal fluid stresses the importance of using highly specific techniques when lipoperoxides are measured in body fluids.
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PMID:Cerebrospinal fluid lipoperoxides quantified by liquid chromatography, and determination of reference values. 229 6

Oxidative stress in brain tissue was measured experimentally in situ using microdialysis to sample the extracellular environment for a lipid peroxidation breakdown product and antioxidants. The extracellular concentrations of the lipid peroxidation product malonaldehyde (MDA) and the antioxidants ascorbic acid (AA) and uric acid (UA) were measured in rat cortex and striatum in vivo using microdialysis coupled to HPLC with UV detection. Tissue acidosis following ischaemia and epileptic seizures may contribute to neuronal damage, which may be mediated by reactive oxygen species. Perfusion of microdialysis probes with acidic artificial cerebrospinal fluid (pH 6) led to a significant increase in the sampled concentration of MDA and the antioxidant ascorbic acid. Simultaneous perfusion of ascorbate (5 mM) with acidic ACSF (pH 6) completely attenuated the rise in lipid peroxidation. This study provides in vivo evidence for acidosis induced oxidative stress in brain tissue and an antioxidant action of ascorbate. The methodology described here can provide direct in vivo information in respect of oxidative stress in experimental situations. The method could equally be applied to the assessment of oxidative stress in a number of pathological models not necessarily confined to the CNS.
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PMID:Acute acidosis elevates malonaldehyde in rat brain in vivo. 870 90

The effects of selective dopaminergic agonists and antagonists on epileptic activity were tested in rats using the lithium/pilocarpine seizure model. Systemic administration of the D1 agonist SKF-38,393 reduced the latency of onset of forelimb clonus with rearing, whereas the D1 antagonist SCH-23,390 and the D2 agonist B-HT 920 prevented the convulsive activity in a dose-dependent manner. Mixed agonists like apomorphine offered partial protection. Haloperidol (D1, D2 blocker, with antimuscarinic property) reduced the threshold for convulsions. The effects of SKF-38,393 and B-HT 920 could be partially blocked by pretreating the rats with SCH-23,390 and sulpiride, respectively. Neither D1 nor D2 antagonists could alter the limbic stereotypies induced by lithium/pilocarpine. These results indicate that dopamine receptor subtypes exert opposite effects on the regulation of convulsive activity. Lipid peroxidation levels (MDA formed) in rat brain homogenates were found to be concomitant with the development of epileptiform activity.
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PMID:Dopaminergic modulation of lithium/pilocarpine-induced status epilepticus in rats. 941 31

Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (Gp) might promote angiogenic response by examining the migration and tube formation in human umbilical cord vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this increase was blocked by antibody to Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting that the angiogenic effects of glycodelin might be mediated by VEGF. The results also showed that Gp significantly increased the release of VEGF protein and mRNA expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin might play an important role in neovascularization during embryogenesis and tumor development.
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PMID:Angiogenic role for glycodelin in tumorigenesis. 1145 32

A rapid, accurate, precise, reproducible, economical, and environmentally gentle method using capillary electrophoresis (CE) is presented for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine in seized drugs. The methodology uses a 32 cm by 50 microm capillary (length to detector 23.5 cm) with a commercially available buffer kit and diode array UV detection. Dynamic coating of the capillary surface is accomplished by flushing with base for 1 min, a proprietary polycation for 1 min, and then a proprietary polyanion for 2 min. This approach provides a relatively high and stable electroosmotic flow (EOF), even at low pHs. The background electrolyte (BGE) contains 75 mM phosphate buffer (pH 2.5) with the same polyanion as above. Using this methodology, amphetamine, methamphetamine, MDA, MDMA, MDEA, and an internal standard (n-butylamphetamine) are baseline resolved in less than 5 min. The run-to-run migration time %RSDs and peak area %RSDs are typically <0.3% and <2.1%, respectively. The day-to-day and capillary-to-capillary migration time %RSDs are <1.5% and <2.1%, respectively. The %RSDs of the relative migration times compared with the internal standard on a day-to-day and capillary-to-capillary basis are <0.2% and <0.06%, respectively. The linear dynamic range using peak areas range from 0.003 to 0.10 mg/mL. The correlation coefficients are >0.9998, with all calibration curves passing at or near the origin. Similar data are obtained for cocaine and its internal standard henyltoloxamine. None of the compounds usually encountered in illicit samples interfere with the target compound (e.g., methamphetamine and cocaine) or the internal standard. Quantitative results for synthetic mixtures and seized exhibits are in good agreement with actual values, and also with results obtained from other techniques. The relatively high EOF for the dynamically coated capillary system allows for the screening of basic, acidic, and neutral adulterants in drug seizures; identification is facilitated by the use of automated UV library searches.
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PMID:Use of dynamically coated capillaries for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary electrophoresis. 1156 40

Cognitive impairment in epileptics may be a consequence of the epileptogenic process as well as antiepileptic medication. Thus, there is a need for drugs, which can suppress epileptogenesis as well as prevent cognitive impairment. In the present study, the effect of aqueous extract of Centella asiatica (CA) (100 and 300 mg/kg), an Indian medicinal plant known to possess antiepileptic, cognitive-enhancing and antioxidant property, was evaluated on the course of kindling development, kindling-induced learning deficit and oxidative stress markers in pentylenetetrazole (PTZ) kindled rats. Male Wistar rats were injected PTZ (30 mg/kg ip) once every alternate day (48+/-2 h) until the development of the kindling. Passive avoidance test and spontaneous locomotor activity were carried out 24 and 48 h after the last administration of PTZ, while the oxidative stress parameters (malondialdehyde [MDA] and glutathione) were carried out in the whole brain upon completion of the behavioral assessment. The administration of CA (300 mg/kg orally) decreased the PTZ-kindled seizures and showed improvement in the learning deficit induced by PTZ kindling as evidenced by decreased seizure score and increased latencies in passive avoidance behavior. However, low dose of the CA (100 mg/kg) showed improvement only in the learning deficit due to the kindling and failed to improve the seizure score. The findings suggest the potential of aqueous extract of CA as adjuvant to antiepileptic drugs with an added advantage of preventing cognitive impairment.
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PMID:Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. 1254 22

In the last decade, a global trend of escalating ecstasy (MDMA, MDA, MDEA, MBDB) use was observed. Mentions on medical death certificates, last year's ecstasy use, number of drug offenders, seizures, prices and dosage levels figures were used for this descriptive and correlational study. Figures (1994-2003) were taken from the UK General Mortality Registers, from the Home Office Statistical Bulletins, from the British Crime Survey and from those reported to both the National Crime Intelligence and Forensic Science Services. A total of 394 ecstasy deaths mentions were here identified from the UK; in 42% of cases ecstasy was the sole drug mentioned. Overall, number of fatalities showed a year-per-year increase and positively correlated with: prevalence of last year's use (p < 0.01); number of offenders (p < 0.01) and number of seizures (p < 0.01) but negatively correlated with ecstasy price (p < 0.05). Price negatively correlated with: prevalence of last year's use (p < 0.001) and number of seizures (p < 0.01); but positively correlated with average MDMA dosage per tablet (p < 0.01). MDA, MDEA and MBDB accounted for a significant proportion of tablets only up to 1997, but not afterwards. Increasing production with a concomitant decrease in ecstasy price may have facilitated an increase in consumption levels and this, in turn, may have determined an increase in number of ecstasy deaths mentions. Only medical death certificates and not coroners' reports at the end of their inquests were here analysed; no data were available in respect of other drugs use and toxicology results.
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PMID:Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices, dosage levels and deaths in the UK (1994-2003). 1657 20

Intoxication with gamma-hydroxybutyrate (GHB) is associated with coma, seizure, and death; treatment of overdoses is symptomatic. Previous studies in our laboratory have demonstrated that L-lactate and pyruvate treatment can increase the renal clearance of GHB and increase its elimination in rats, suggesting that GHB may undergo renal reabsorption mediated by monocarboxylic acid transporters (MCTs). The goals of this study were to characterize the renal transport of GHB in rats and to determine the role of MCT in its renal transport. Brush-border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from rat kidney cortex, and the uptake of L-lactate and GHB was characterized. L-Lactate and GHB undergo both pH- and sodium-dependent transport in BBM vesicles and pH-dependent transport in BLM vesicles. A simple Michaelis-Menten equation best described the pH-dependent uptake of GHB in BBM (Km, 8.0 +/- 1.8 mM; Vmax, 838 +/- 45 pmol/mg/s) and in BLM vesicles (Km, 10.5 +/- 2.6 mM; Vmax, 806 +/- 253 pmol/mg/s). mRNA of MCT1 and MCT2 was determined in rat kidney cortex using reverse transcriptase-polymerase chain reaction; using Western blot, the protein expression of MCT1 was present mainly in BLM vesicles, with weak expression in BBM vesicles, whereas that of MCT2 was exclusively in BLM vesicles. Studies with rat MCT1 gene-transfected MDA-MB231 cells demonstrated that GHB was a substrate of MCT1. The data suggest that rat MCT1 may represent an important transporter for GHB in renal tubule cells. This investigation provides evidence for the importance of MCTs in the reabsorption of the monocarboxylic acids l-lactate and GHB in the kidney.
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PMID:Transport of gamma-hydroxybutyrate in rat kidney membrane vesicles: Role of monocarboxylate transporters. 1670 23

Free radicals play a crucial role in health and disease and both reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in CNS effects like excitotoxicity. Theophylline, a re-emerging drug for the treatment of obstructive airway disease, has a narrow therapeutic index which precludes its safe use. The present study evaluated the possible involvement of free radicals in theophylline induced seizures in mice. Aminophylline (100-250 mg/kg) consistently induced seizures and post-ictal mortality, and conventional anticonvulsants and adenosine agonists were ineffective in antagonizing them. Further, phosphodiesterase inhibitors, per se, also did not show any significant seizurogenic potential. Pretreatments with antioxidants, ascorbic acid, alpha-tocopherol and melatonin, all dose dependently reduced seizure incidence and mortality after aminophylline, whereas, antioxidant depletion potentiated such excitotoxicity. Pretreatments with the NO synthase inhibitors, L-NAME and 7-NI blocked aminophylline seizures, whereas, the NO mimetics, L-arginine and glyceryl trinitrate, tended to potentiate this phenomenon. Sub-effective doses of aminophylline (100 mg/kg) also induced seizures when combined with subthreshold intensity of electroshock, and such seizures were similarly antagonized by the antioxidants and NO synthase inhibitors. Biochemical assay of brain homogenates showed that aminophylline seizures were associated with enhancements in brain MDA and NOx (NO metabolites) levels, whereas, SOD activity was reduced, and these changes were attenuated after melatonin and L-NAME pretreatments. The pharmacological and biochemical data are strongly suggestive of the involvement of both ROS and RNS during theophylline-induced seizures.
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PMID:Free radicals and theophylline neurotoxicity : an experimental study. 1754 32

The present study was conducted to investigate the possible interaction between low doses of nicotine and pentylenetetrazole (PTZ) in vivo and also to evaluate the influence of nicotine on the antiseizure efficacy of topiramate and sodium valproate in the PTZ-induced seizure model in mice. Graded dose-response study with nicotine showed the CD50 value for nicotine at 6.76 mg/kg. i.p. Subtheshold dose of nicotine (4 mg/kg, i.p.) pretreatment significantly decreased the CD50 value for PTZ from 47.86 mg/kg, i.p. (of PTZ per se) to 31.62 mg/kg, i.p. Sodium valproate but not topiramate, significantly inhibited PTZ-induced seizures in mice with an ED50 value of 177.83 mg/kg, i.p. Nonconvulsive dose of nicotine (1 mg/kg, i.p.) significantly antagonized the protective efficacy of sodium valproate against PTZ-induced seizures and increased the ED50 value to 338.84 mg/kg, i.p. PTZ-induced seizures significantly increased the mouse brain levels of MDA and reduced the level of GSH while sodium valproate reversed such changes. Nicotine pretreatment reversed the anti-lipid peroxidative action of sodium valproate in the PTZ-induced seizure model in mice. The study highlighted the convulsant as well as proconvulsant role of nicotine and established dose discrimination for nicotine as a proconvulsant agent and an anti-antiseizure agent. The study bears significant clinical relevance particularly amongst epileptic smokers who may show failure of efficacy of antiepileptic agents and present with breakthrough seizure attacks on exposure to nicotine.
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PMID:Dose-finding study with nicotine as a proconvulsant agent in PTZ-induced seizure model in mice. 1866 46


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