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)

Acute hypertension increases the cerebrovascular permeability to protein to a higher extent in anesthetized than in conscious rats. When hypertension is combined with a pronounced cerebral vasodilatation, e.g. in bicuculline-induced seizures, the protein leakage is enhanced. Conscoius, unrestrained 2--3-months-old rats received adrenaline or bicuculline i.v. during continuous recording of the mean arterial pressure and were killed 3 minutes later. Rats, neonatally sympathectomized by 6-hydroxydopamine, had significantly increased extravasation of 125I serum albumin in the brain after adrenaline-induced hypertension than nonsympathectomized rats. Since transection of the cervical sympathettic trunk alone does not have the same effect, a protection of the blood-brain barrier in acute hypertension in conscious rats may, at least in part, be mediated via the central noradrenergic innervation of cerebral vessels. Bicuculline did not increase blood pressure in 6-OHDA treated rats; thus the blood-brain barrier remained intact.
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PMID:Neonatal 6-hydroxydopamine treatment increases the vulnerability of the blood-brain barrier to acute hypertension in conscious rats. 4 65

In the four years between 1972 and 1976 twenty out of 160 maintenance dialysis patients developed dialysis dementia. Their illness was characterized by an insidious onset of mental deterioration, speech disturbance, apraxia, and myoclonus. The disease progressed inexorably to a fatal outcome, the onset of seizures being an ominous sign, and the average duration of the illness being seven months. Routine biochemical studies were unremarkable, and osteodystrophy was not a prominent feature. Serial electroencephalograms (EEG) showed progressive slowing of the rhythm, usually antedating the neurologic symptoms. Brain scan and flow studies were normal. Radio-iodinated serum albumin (RISA) scans in seven patients showed changes suggesting altered cerebrospinal fluid (CSF) dynamics. Treatment was generally ineffective, but ventriculo-peritoneal shunting produced transient neurologic improvement in one patient. Epidemiologic investigations showed high aluminum levels in city water during the period of the outbreak.
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PMID:Dialysis dementia -- the Chicago experience. 75 Jun 11

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.
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PMID:Inhibition of GABA-gated chloride channel function by arachidonic acid. 132 73

Several experiments were designed to evaluate a secondary humoral response following limbic seizures. After baseline antigen binding capacity (ABC) had been determined for the primary response, a second subcutaneous injection of the antigen (human serum albumin) was accompanied by an injection of either lithium (3 mEq/kg)-pilocarpine (30 mg/kg) or one of two comparator treatments: metrazol (30 mg/kg) or cyclophosphamide (50 mg/kg); other rats served as drug controls. Only the groups that received the lithium-pilocarpine (status epilepticus) or cyclophosphamide (no seizure) displayed significant immunosuppression after 5 but not 10 days. The results support the hypothesis that seizure activity within the amygdaloid-hippocampal complex modulates immunocompetence through corticotropin mechanisms.
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PMID:Transient suppression of a secondary humoral response in rats is evoked by lithium-pilocarpine-induced limbic seizures. 132 17

White rats were immunized against fragment of diazepam-binding inhibitor octadecaneuropeptide (ODN) with conjugate ODN bovine serum albumin. This rats have reduced reactions of fear and anxiety in stress model of "open field" and in conflict Vogel test; their pain sensitivity ("tail flick" test) was lowered. The number and intensity of generalized seizure reactions after injection of pentylenetetrazole were decreased. The results show that active immunization to endogenous ODN has stress--protective and anti-seizure effects.
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PMID:[Increase of seizure threshold and resistance to stress in rats after immunization against fragment of diazepam-binding inhibitor]. 142 Dec 24

The influence of white rats immunization by a covalent conjugate of serum albumin with sydnophen on the seizure activity in the single and repeated injections of pentylenetetrazole was investigated. The immunization lowered the seizure activity in single injections of threshold doses, (60 mg/kg) of pentylenetetrazole. The repeated daily injections of the drug in subthreshold doses (30 mg/kg) inhibited the process of "kindling" effects formation.
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PMID:[The convulsive activity of white rats after immunization with a conjugate of sidnofen and serum albumin]. 185 53

We report 12 adults with seizures associated with serum theophylline levels between 14 and 35 mg/l. The seizures were frequently prolonged, and outcome was generally poor with eight deaths. Although we did not identify comparable control groups, possible risk factors for serious outcome in theophylline-associated seizures were age, previous brain injury or disease, severe pulmonary disease, and possibly low serum albumin level. In patients with these risk factors, serum theophylline levels should be maintained below 10 to 15 mg/l.
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PMID:Theophylline-associated seizures with "therapeutic" or low toxic serum concentrations: risk factors for serious outcome in adults. 140 96

Seizure prophylaxis is standard intrapartum therapy for patients with pregnancy-induced hypertension. Magnesium sulfate is used in the United States in spite of limited literature comparing its efficacy with other anticonvulsants. Fifty patients with pregnancy-induced hypertension were prospectively randomized to receive magnesium sulfate or phenytoin for seizure prophylaxis. Patients were observed for toxicity, side effects, and labor outcomes, and the neonates were evaluated for side effects of the therapy. Three patients were excluded with adverse reactions to medications (one in magnesium sulfate group, two in phenytoin group). No differences were found in patient tolerance, adverse reactions, or neonatal outcomes between groups. Maternal free phenytoin levels were 13.0% +/- 0.4% of total phenytoin (serum albumin, 2.5 to 3.5 gm/dl), significantly higher than in nonpregnant patients. Neither free phenytoin levels nor percentage of total phenytoin that was free correlated significantly with maternal albumin levels. The pharmacokinetics of phenytoin loading in the massively obese pregnant patient may differ and require further evaluation. Phenytoin is a well-tolerated alternative to magnesium sulfate for seizure prophylaxis in the patient with mild pregnancy-induced hypertension.
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PMID:Magnesium sulfate versus phenytoin for seizure prophylaxis in pregnancy-induced hypertension. 195 52

The relationships between total and free serum concentrations of phenytoin and the clinical control of seizures were investigated retrospectively in 114 patients. Total phenytoin levels were measured by enzyme-modified immunoassay (EMIT), and the free fraction by ultrafiltration at 37 degrees C using 14C-labelled phenytoin as a tracer. The median free fraction in 188 serum samples was 13.7% (range 8.9-27.0%). The free fraction was greater than 18% in 34 (18.1%) of the serum samples. In all but 5 samples, a likely reason for the elevated free fraction could be determined. The identifiable reasons were commonly hypoalbuminaemia and the presence of liver or renal disease. There was a significant negative correlation between serum albumin level and free fraction of phenytoin (n = 90, r = -0.68, p less than 0.001). The free phenytoin concentration was strongly correlated with the total phenytoin concentration in serum (n = 188, r = 0.94, p less than 0.001). The total phenytoin concentration provided as good an indication of clinical response as the free concentration in 91 patients (85.8% of the patients for whom response could be reliably determined). In the other 15 (14.2%) patients, free phenytoin concentrations were better related to clinical effect. These patients generally had significant reductions in the serum protein binding of phenytoin. The relationship between phenytoin toxicity and free serum concentrations was particularly strong--in 14 patients with toxicity, the total serum concentration of phenytoin was greater than 80 mumol/L in only 42.9% of cases, while the free phenytoin concentration was greater than 8 mumol/L in 85.7% of the cases (p less than 0.05 by chi-square test).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical response in epilepsy in relation to total and free serum levels of phenytoin. 195 33

Phenytoin (DPH) is commonly used to treat seizures associated with acute head injury. Consequent to decreases in DPH protein binding in such patients, the DPH free fraction (DPHff) may increase and thereby produce symptoms compatible with DPH toxicity despite the presence of total serum concentrations within the usually accepted therapeutic range. We examined the effect of acute traumatic injury on DPH protein binding in 13 hospitalized pediatric patients. In addition to total and free DPH serum concentrations, biochemical variables including blood pH, total and direct bilirubin, serum urea nitrogen, creatinine, albumin, gamma glutamyltransferase (GGT), and free fatty acid concentrations were measured serially over 10 days. The DPHff was compared between selected time intervals in hospitalized patients and data obtained in a control population of 27 epileptic outpatients who were maintained on DPH. Additionally, a multiple regression model was used to examine for covariance between the DPHff and the respective biochemical variables in the hospitalized patients. In the study patients, the DPHff progressively increased, attaining a maximum value (8.5 +/- 0.7%) on the fifth hospital day which was significantly greater (6.4 +/- 0.7%, p less than .05) than that on day 1 and also in the control group (6.1 +/- 0.3%; p less than .01). Blood pH, serum albumin, free fatty acids, creatinine and bilirubin concentrations did not change, but GGT did increase significantly over the 10-day sampling period. A significant (r = .51, p less than .0001) linear relationship was found between the DPHff and the serum albumin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenytoin protein binding in pediatric patients with acute traumatic injury. 196 39


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