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)

When glucose utilisation is impaired due to decreased insulin effect, ketones are produced by the liver from free fatty acids to supply an alternate source of energy. This adaptation may be associated with severe metabolic acidosis and tends to occur in patients with type I (insulin-dependent) diabetes mellitus. In addition, hypovolemia is an almost invariable finding with marked hypoglycemia and is primarily induced by the associated glucosuria. Ketoacidosis stimulates both the central and peripheral chemoreceptors controlling respiration, resulting in alveolar hyperventilation (Kussmaul's respiration). With the ensuing fall in pCO2 the patient tries to raise the extracellular pH. A fruity odor of acetone on the patient's breath sometimes suggests that ketoacidosis is present. The classical triad of symptoms associated with hyperglycemia are polyuria, polydipsia, and weight loss. Circulatory insufficiency with hypotension is not uncommon due to the marked fluid loss and acidemia. In more severely affected patients, neurologic abnormalities may be seen, including lethargy, seizures or coma. Some patients also have marked vomiting and abdominal pain. The history and physical examination may provide important clues to the presence of uncontrolled diabetes mellitus. Once suspected, the diagnosis can be easily confirmed by measuring the plasma glucose concentration. Glucosuria and ketonuria can be semiquantitatively detected with reagent sticks. Blood gas analysis and anion gap give objective information as to the severity of the metabolic acidosis. Therapy must be directed toward each of the metabolic disturbances: hyperosmolality, ketoacidosis, hypovolemia and potassium, and phosphate depletion. The mainstays of therapy are the administration of low-dose insulin and volume repletion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Ketoacidotic diabetic metabolic dysregulation: pathophysiology, clinical aspects, diagnosis and therapy]. 817 67

We have previously shown that in the adult rat the inhibition of brain glutamate decarboxylase (GAD) activity by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH) administration does not result in convulsions, whereas in the adult mouse intense convulsions invariably occur. In the present study we report that, surprisingly, immature rats from 2 to 20 days of age treated with PLPGH (80 mg/kg) showed generalized tonic-clonic convulsions, whereas no convulsions at all were present in 30 days-old or older rats. GAD activity, measured by enzymic determination of GABA formed in forebrain homogenates, was inhibited by about 60% at the time of convulsions in 15 days-old and younger rats, whereas the inhibition was between 40 and 50% in older animals. The addition of the coenzyme pyridoxal 5'-phosphate to the incubation medium completely reversed this inhibition. In all treated animals GABA levels were lower compared to controls. The results indicate that the susceptibility of GAD in vivo to a diminished cofactor concentration decreases with age. It seems possible that changes in the expression of enzyme forms are reflected in developmental variations in the susceptibility to seizures induced by vitamin B6 depletion, but alterations of other B6-dependent biochemical pathways cannot be discarded.
 ...
PMID:Convulsions and inhibition of glutamate decarboxylase by pyridoxal phosphate-gamma-glutamyl hydrazone in the developing rat. 818 28

With suicidal intent a 72-year-old man swallowed 5.8 g aminophylline in a non-retard solution. The theophylline plasma level on admission was 120 mg/l. He had to be intubated when respiratory arrest occurred. Within the first hour he developed cerebral seizures, polymorphous ventricular premature systoles, atrial fibrillation with an irregular ventricular rate and, finally, recurrent episodes of ventricular fibrillation with prolonged circulatory shock (heart rate 120-140/min with a systolic blood pressure of 60 mm Hg for 3 hours) and severe metabolic acidosis (potassium 2.28 mmol/l, phosphate 0.21 mmol/l, pH 7.03, base excess -20.8 mmol/l). He was treated with massive fluid replacement (6.2 l in the first 12 hours), electrolyte substitution to counteract the marked hypokalaemia and hypophosphataemia, repeated defibrillation and antiarrhythmic drugs (lidocaine 240 mg/h and metoprolol twice 5 mg), as well as anticonvulsive treatment (diazepam, 10 mg twice, followed by midazolam 5 mg/h). Detoxication measures consisted initially of gastric lavage followed by high-dosage enteric administration of charcoal (210 g over 36 h), as well as haemoperfusion for 4 h. Full recovery was achieved and the patient was discharged in good health after 3 weeks.
 ...
PMID:[The clinical course and therapy of massive theophylline poisoning]. 822 24

MIL-L-23699 lubricants that are composed principally of trimethylolpropane triheptanoate (TMP) and tricresyl phosphate (TCP) have been shown to form a neurotoxicant, trimethylolpropane phosphate (TMPP), during pyrolysis and/or combustion. Mechanistically, TMPP is thought to irreversibly inhibit the GABA-mediated inhibitory response and thereby produce epileptiform clonic/tonic seizures with convulsions followed by death. Thermal decomposition of MIL-L-23699 lubricant produces TMPP under laboratory conditions, but this product has not been detected in the workplace following actual fires. This study has examined whether TMPP is produced during an actual shipboard fire by placing the synthetic lubricant in a fire environment aboard the ex-U.S.S. Shadwell, Mobile, Alabama. Both biological and chemical analyses were performed on the thermally decomposed lubricant to ensure detection of the neurotoxic material. Under the conditions of this study, the formation of TMPP during a shipboard fire was confirmed. The implications of this finding for safe management of post-fire cleanup are discussed.
 ...
PMID:Evaluation of shipboard formation of a neurotoxicant (trimethylolpropane phosphate) from thermal decomposition of synthetic aircraft engine lubricant. 823 91

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEG recording and in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of > 30-Hz and of 4-5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electrographic spikes appeared at increasing frequency, progressing to high-amplitude (0.1-0.8 mV) continuous seizure activity (status epilepticus). In ventilated mice, the [31P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was followed by a marked decrease in EEG amplitude that progressed rapidly to isoelectric silence. [31P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was accompanied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 +/- 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.
 ...
PMID:Phosphate energy metabolism during domoic acid-induced seizures. 824 72

Both clinical and laboratory studies are being undertaken to investigate the deleterious neurologic and developmental effects associated with cardiopulmonary bypass, hypothermia, and circulatory arrest in the neonate and infant. A prospective, randomized clinical study of 171 neonates and young infants compared circulatory arrest with low-flow bypass (50 mL.kg-1.min-1). Circulatory arrest was associated with a higher incidence of early postoperative seizures as well as greater release of creatine kinase-BB. There was a strong correlation between duration of circulatory arrest and seizures (p = 0.004). The late consequences of these findings will be known at the completion of developmental assessment of all patients at 1 and 4 years of age. Laboratory studies have used a miniature piglet model that closely replicates clinical circulatory arrest. High-energy phosphate stores determined by magnetic resonance spectroscopy were maintained in animals undergoing 1 hour of low-flow bypass but became undetectable after 32 minutes of a 1-hour period of circulatory arrest. However, they returned to baseline within 3 hours of reperfusion as did cerebral blood flow and metabolism determined by microsphere studies. Piglets undergoing 1 hour of circulatory arrest showed more rapid recovery of cerebral adenosine triphosphate content and intracellular pH when managed with the pH-stat strategy during hypothermic bypass than with the more alkaline alpha-stat strategy. Other laboratory studies have examined pharmacologic methods of reducing cerebral injury associated with circulatory arrest including aprotinin, anti-CD18, neuronal receptor antagonists (MK801, NBQX), and blockade of glutamate release with adenosine in a cerebroplegia solution. These studies have suggested a number of promising approaches to improving the technique of circulatory arrest.
 ...
PMID:Review of current research at Boston Children's Hospital. 826 70

Three cases with distinct clinical manifestations associated with rhabdomyolysis syndrome were encountered in this hospital's pediatric intensive care unit. Elevation of serum creatine phosphokinase, uric acid, potassium, inorganic phosphate and hypocalcemia with seizure were noted. The three patients all had signs of acute renal failure. One died of respiratory failure, and autopsy revealed multiple intrathoracic anomalies. The remaining two recovered completely from rhabdomyolysis. It is of importance to early recognize any acutely ill patient as having rhabdomyolysis syndrome when there is elevation of muscle enzymes, hypocalcemic seizure, positive orthotolidine reaction of urine strip while negative finding of red blood cell. The syndrome may damage the kidneys. Appropriate management to induce diuresis usually can salvage this potentially life-threatening condition.
 ...
PMID:Rhabdomyolysis syndrome in children: report of three cases. 836 67

Neutral and alkaline phosphatase activities were studied in small synaptosomes isolated from rat brain and cerebellum after administration of the convulsant 3-mercaptopropionic acid (MP). Cerebral cortex phosphatase activity assayed at pH 7.2 in the presence of K+ increased both during and after seizures; when it was assayed at pH 7.2 in the absence of K+ it decreased at both stages. The enzyme activity determined in cortical fractions at pH 9.0 with or without K+ decreased in seizure and postseizure states. After MP treatment, cerebellum enzyme activity assay at pH 7.2 was higher than in controls throughout; phosphatase activity assayed at pH 9.0 decreased following MP administration except during seizures when the enzyme was assayed in the presence of K+. Such changes following MP treatment may well be related to seizure-induced alteration of phosphate ester levels or protein-kinase activities.
 ...
PMID:Differential changes in CNS phosphatase activities during seizures. 838 17

Alterations in the energy state and glucose metabolism of hippocampal slices exposed to high extracellular K+ ([K+]o) were monitored using 31P and 13C NMR spectroscopy. Slices were perfused (37 degrees C) continuously within the NMR spectrometer and tissue viability and metabolic activity were maintained for at least 18 h. 31P spectra showed that upon exposure to 40 mM [K+]o, there was a rapid compromise in tissue energetics where, by 15 min of exposure, the ratio of phosphocreatine and of nucleoside triphosphates to inorganic phosphate (extra- and intracellular) decreased 30-50% relative to pre-exposure values. This was accompanied by a pH decrease of approximately 0.3 units in both the intra and extracellular environments. A lower but stable energy state was reached at approximately 15 min of exposure and full recovery was observed by 30 min following the removal of high [K+]o. Utilizing 13C NMR in the presence of [1-13C]glucose, an immediate and dramatic acceleration in tissue glycolysis was observed when slices were exposed to 40 mM [K+]o: the rates of both [1-13C]glucose consumption and [3-13C] acetate synthesis increased by approximately 20 fold. By 60 min following the removal of high-[K+]o, pre-exposure rates of tissue glycolysis were restored. The results indicated that the rapid and dramatic induction of energy production via glycolysis probably accounts for the ability of hippocampal slices to maintain viability and recuperate from brief but intense depolarizing conditions which are reminiscent of seizure states in vivo.
 ...
PMID:Energetics and glucose metabolism in hippocampal slices during depolarization: 31P and 13C NMR studies. 851 24

The behavioral consequences of metabotropic glutamate receptor (mGluR) activation were investigated following intracerebral administration of the mGluR selective agonists (RS)3,5-dihydroxyphenyl-glycine (3,5-DHPG), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), (1R,3S)-1-aminocyclopentane-1,3-dicarboxylate (1R,3S-ACPD), L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP) and (2S,3S,4S)alpha-(carboxycyclopropyl)glycine (L-CCGI) into the thalamus in mice. Injections of 3,5-DHPG, 1S,3R-ACPD and L-CCGI produced dose-dependent increases in limbic seizures with a potency order of 3,5-DHPG = 1S,3R-ACPD > L-CCGI. This effect of 1S,3R-ACPD was stereoselective, since the inactive isomer (1R,3S-ACPD) did not elicit seizure activity. Limbic seizures induced by the phosphoinositide-coupled mGluR subtype selective agonist 3,5-DHPG were attenuated by the mGluR antagonist L-2-amino-3-phosphonopropanoic acid (L-AP3) and dantrolene, inhibitors of mGluR-mediated intracellular calcium mobilization. Interestingly, L-AP4, L-SOP and low doses of L-CCGI also protected against 3,5-DHPG seizures. These data indicate that mGluR agonist-induced limbic seizures in mice are mediated by activation of phosphoinositide-coupled mGluRs. Furthermore, these seizures can be protected against by activation of mGluRs that are negatively-linked to cAMP formation.
 ...
PMID:Induction or protection of limbic seizures in mice by mGluR subtype selective agonists. 853 55


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