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)

Congenital duodenal webs are rare lesions, usually detected during early infancy because of signs of high intestinal obstruction. The occasional patient escapes both symptoms and detection until adolescence or adulthood. This report concerns two cases of congenital duodenal web at different ages and with different clinical manifestations. Case 1, a six-month-old male, was admitted because of abdominal distention and vomiting. Case 2, a 13-year-old boy, was referred here for further evaluation of recurring seizure attacks, elevated blood urea nitrogen and creatinine and hyponatremia. Duodenotomy and excision of the web performed for both patients. Complete amelioration of all symptoms was then observed at Outpatient Clinic follow-up for one year.
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PMID:Congenital duodenal web in late infancy and childhood: a report of two cases. 803 46

Pretreatment of mice with 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase, diminishes the accumulation of ammonia in the brain after administration of ammonium acetate, and antagonizes ammonia-induced fatal tonic extensor convulsions. In about 50% of the treated animals the loss of the righting reflex and coma is prevented. Presumably these effects are based on the enhancement of urea formation by the increased liver ornithine concentrations. However, since brain ornithine concentrations are greatly enhanced by 5FMOrn, it is not excluded that ornithine has direct effects on cellular events involved in ammonia-induced seizure generation, even though 5FMOrn had no anticonvulsant properties in a series of established animal seizure models, including N-methyl-D,L-aspartate-induced convulsions. NMDA receptor antagonists are capable of preventing death, but do not protect against the generation of coma and tonic extensor convulsions in ammonium acetate intoxicated mice. Since no evidence was found for ammonia-induced glutamate release from rat hippocampus, there is no convincing evidence for the idea that the tonic convulsions are mediated by NMDA receptors. L-Methionine-D, L-sulfoximine (MSO)-induced seizures can be partially antagonized by pretreatment with 5FMOrn. However, the effect is considerably smaller than against ammonia-induced convulsions, although at the time of seizure onset brain ammonia levels of MSO-intoxicated mice were lower than in the animals receiving ammonium acetate. This suggests that MSO-convulsions are not entirely due to the elevation of brain ammonia concentrations, even though MSO administration mimics effects of ammonia on cortical inhibitory neuronal interactions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced endogenous ornithine concentrations protect against tonic seizures and coma in acute ammonia intoxication. 809 10

In an effort to detect active renal tubular dysfunction in 74 epileptic patients being treated with antiepileptic drugs (AEDs), we measured the urinary activity of two lysosomal enzymes, N-acetyl-beta-glucosaminidase (NAG) and beta-galactosidase (beta-gal). The heterogeneity of the types of seizures and therapeutic regimens permitted us to examine the potential differences in AED effects. We also examined the chronological changes in the urinary excretion rates of NAG and beta-gal in 132 healthy controls, aged 3 months to 37 years. Increased NAG excretion rates (defined as > or = 2 S.D. compared with age-matched controls) were found in 36.5% of the patients. Valproic acid was highly associated with this increase, and in combination with potassium bromide caused the highest levels of NAG excretion. Among the patients taking carbamazepine, only 11.1% exhibited high levels of NAG in urine. Children under 1 year of age showed higher levels of NAG excretion than older patients. In spite of the abnormally high urinary excretion of NAG, we could not detect any signs of renal dysfunction by urinalysis and measurement of blood urea nitrogen and serum electrolytes. We cannot exclude the possibility that the increased levels of urinary NAG in epileptic patients might be due to renal tubular enzyme induction by AEDs.
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PMID:Urinary excretion of N-acetyl-beta-glucosaminidase and beta-galactosidase by patients with epilepsy. 821 37

Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D-carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia.
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PMID:Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. 834 26

This paper describes the signs of toxicity when seed-bearing flatpea (Lathyrus sylvestris L) hay is fed to sheep. Signs of intoxication (including seizure, muscular trembling and spasmotic torticollis) are similar to those observed for ammonia toxicity in ruminants. Accumulation of ammonia may be a direct consequence of flatpea ingestion, given that 2,4-diaminobutyric acid (DABA, a toxic constituent of flatpea) is known to inhibit hepatic urea synthesis. However, other modes of toxicity for DABA as well as other flatpea toxins may also contribute to this process of intoxication. Our evidence suggests that ruminal microbes are responsible for flatpea detoxification and host animal protection. The adaptation of sheep to flatpea may be a consequence of enhanced ruminal detoxification activity. Ruminal protective functions can be disrupted, however, through abrupt monensin feeding or the replacement of nonadapted for adapted rumen contents. This disruption temporarily suppresses mechanisms of ruminal detoxification. As a consequence sheep can again be made vulnerable to flatpea intoxication.
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PMID:Flatpea intoxication in sheep and indications of ruminal adaptation. 847 Mar 53

By the end of a dialysis session the patient had a generalized convulsive seizure. Then meningeal syndrome, right-sided hemiparesis with central lesion of right facial nerve and bilaterally positive extensor plantar response were found. Because of the increase of blood pressure and then increased body temperature the diagnosis of acute hyponatraemic encephalopathy was not made only on the basis of the plasma ionogram (Na+ 110mEq/1) but also after excluding possible subarachnoid haemorrhage and acute cerebrospinal meningitis and encephalitis by cerebrospinal fluid examination. Hyponatraemia found in some patients suffering from chronic renal insufficiency is increased by haemodialysis session. Cerebral oedema which is proportional to natraemia is caused by urea disolation from intracellular to extracellular fluid. This process increases concentration gradient between intracellular and extracellular fluids. The perceptible neurological signs occur as natraemia declines below 120 mEq/l.
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PMID:[Acute hyponatraemic encephalopathy in a patient on chronic hemodialysis program -- a case report]. 850 50

A series of imidazo[1,5-a]quinoxaline amides, carbamates, and ureas which have high affinity for the gamma-aminobutyric acid A/benzodiazepine receptor complex was developed. Compounds within this class have varying efficacies ranging from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [35S]TBPS and Cl- current ratios. Many of these compounds were also effective in antagonizing metrazole-induced seizures in accordance with anticonvulsant and possible anxiolytic activity. Selected quinoxalines displayed limited benzodiazepine-type side effects such as ethanol potentiation and physical dependence in animal models. Dimethylamino urea 41 emerged as the most interesting analog, having a partial agonist profile in vitro while possessing useful activity in animal models of anxiety such as the Vogel and Geller assays. In accordance with its partial agonist profile, 41 was devoid of typical benzodiazepine side effects.
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PMID:High-affinity partial agonist imidazo[1,5-a]quinoxaline amides, carbamates, and ureas at the gamma-aminobutyric acid A/benzodiazepine receptor complex. 856 3

Mitochondria of fibroblasts cultured from the skin obtained at biopsy from three patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome, one of the autosomal recessive, heritable urea cycle disorders, were studied with appropriate controls ultrastructurally. The patients were two severely retarded 10- and 12-year-old boys, and a 22-year-old sister of the former whose mental status was at the low normal range; she never had motor impairments or seizures. The mitochondria, similar in all three patients, were increased in number, very long, branching and/or "looping," and tortuous. "Spurs" or "buddings" extended from their lateral surfaces and the terminal segments were often bulbous. Other unusual configurations were also present. In addition, giant forms with large diameter contained innumerable closely-packed and parallel cristae which traversed the entire width of these mitochondria; at times they assumed a "whirled" pattern. The mitochondrial matrix was usually of high electron density. These changes were not a feature of fibroblastic mitochondria of controls. Several changes resembled those of hepatic mitochondria in this disorder. All features are interpreted as an attempt at expanding the mitochondrial volume (via structural substratum) to compensate for the metabolic incompetence of these organelles (a block in transmembranous transfer of ornithine from hyaloplasm into mitochondria for conversion to citrulline).
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PMID:Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome. Ultrastructural changes of mitochondria in cultured dermal fibroblasts of three patients. 873 74

A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo[1,5-alpha]quinoxaline urea series had high affinity for the GABAA/benzodiazepine receptor complex with varying in vitro efficacy, although most analogs were partial agonists as indicated by [35S]TBPS and Cl- current ratios. Interestingly, a subseries of piperazine ureas was identified which had biphasic efficacy, becoming more antagonistic with increasing concentration. Analogs within the imidazo[1,5-alpha]quinoxalin-4-one series had substantially decreased binding affinity as compared to the quinoxaline urea series. These compounds ranged from antagonists to full agonists by in vitro analysis, with several derivatives having roughly 4-fold greater intrinsic activity than diazepam as indicated by Cl- current measurement. Numerous compounds from both series were effective in antagonizing metrazole-induced seizures, consistent with anti-convulsant properties and possible anxiolytic activity. Most of the quinoxaline ureas and quinoxalin-4-ones were active in an acute electroshock physical dependence side effect assay in mice precluding further development.
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PMID:3-Phenyl-substituted imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas that have high affinity at the GABAA/benzodiazepine receptor complex. 880 70

Patients with hyponatremia are exposed to major neurological complications. On the one hand hyponatremia itself produces brain edema, increased intracranial pressure which potentially leads to subsequent neuropathological sequelae or death. On the other hand excessive correction could be followed by development of brain demyelinating lesions (central pontine or extrapontine myelinolysis) with major disability or fatal outcome. Understanding of brain adaptative mechanisms to changes in osmolality largely contributes to explain these neurological events. When serum sodium decreases, the brain prevents swelling by extruding electrolytes and organic osmolytes, a process almost fully achieved after 48 h. Conversely, during subsequent increase in serum sodium, reestablishment of intracerebral osmolytes occurs but their reuptake is more delayed (+/- 5 days). In both circumstances, these mechanisms can be overwhelmed, leading to brain damage. Acute hyponatremia (< 48 h) is generally hospital-acquired, mainly in the postoperative state and/or after excessive fluid administration. After abrupt fall in serum sodium, seizure, respiratory arrest and coma may develop and these manifestations are sometimes explosive in nature. Recognition of even minor symptoms is crucial and implies prompt correction. There is generally no risk of brain myelinolysis in acute hyponatremia. Some factors are suspected to aggravate the prognosis of hyponatremic encephalopathy, including female gender (menstruant women), hypoxia and young age. Chronic hyponatremia (> 48 h) usually develops outside the hospital and is generally better tolerated. The risks of brain myelinolysis can be largely reduced by limiting the correction level to < or = 15 mEq/1/24 h. However, if necessary, the initial rate of correction can be rapid provided that the final correction remains < 15 mEq/1/24 h. However, when other recognized risk factors for myelinolysis (hypokalemia, liver disease, poor nutritional state, burns) are present, correction should not exceed 10 mEq/1/24 h. Demyelinization is also observed in hypernatremia but it follows greater (50%) increase in serum sodium than from hyponatremic baseline. For symptomatic hyponatremia, rapid correction is usually obtained by hypertonic saline (3%) infusion. Another option consists in administration of intravenous or oral urea. Urea allows a rapid reduction of brain edema and intracranial pressure which is followed by subsequent correction of hyponatremia. Experimental data also suggest that treatment of hyponatremia with urea is associated with a lower incidence of myelinolysis. In hyponatremic patients without symptoms, there is no need for rapid correction and the treatment should be more conservative. Close monitoring of the serum sodium is indicated initially and if necessary, correction must be stopped and diuresis interrupted with dDAVP. Given recent experimental data, in patients overly corrected (delta SNa > 15 mEq/1/24 h), the risk of myelinolysis could be greatly reduced by rapidly decreasing the serum sodium through hypotonic fluids administration and dDAVP.
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PMID:Therapeutic recommendations for management of severe hyponatremia: current concepts on pathogenesis and prevention of neurologic complications. 887 50


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