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)

An acute toxic interaction has been described, in which sublethal doses of pyridostigmine bromide (PB) and the insect repellent N,N-diethyl-m-toluamide (DEET), when administered concomitantly, resulted in seizures and lethality. To investigate the possible relationships between seizures and lethality and the role of the cholinergic system in this interaction, PB (5 mg/kg), DEET (200 mg/kg) or PB (3 mg/kg) + DEET (200 mg/kg) were administered i.p. to male ICR mice, alone or following i.p. pretreatment, with one of several anticonvulsant agents: diazepam, 10 mg/kg; fosphenytoin, 40 mg/kg; phenobarbital, 45 mg/kg; or dextrophan, 25 mg/kg), or the anticholinergic agents, atropine (5 mg/kg), atropine methyl nitrate (2.7 mg/kg), or mecamylamine (2.5 mg/kg). The anticonvulsants selected for this study act through different mechanisms to reduce seizures. None of the anticonvulsants was able to reduce the incidence of seizures following treatment with PB, DEET or PB + DEET. Only diazepam delayed the onset of seizures. Fosphenytoin or diazepam significantly prolonged the time to lethality following PB, but only fosphenytoin reduced the incidence of PB-induced lethality. Diazepam or phenobarbital significantly prolonged the time to lethality following PB + DEET. Both atropine and atropine methyl nitrate protected against PB and PB + DEET-induced lethality and PB-induced seizures. Neither agent blocked seizures resulting from DEET or PB + DEET. Mecamylamine reduced seizures and lethality in PB-treated mice, but not in mice treated with DEET or PB + DEET. The results indicate that seizure activity is not a causative factor in the toxic interaction between PB and DEET. Furthermore, PB, DEET and PB + DEET induce seizures that are resistant to standard anticonvulsants, and each appears to operate through different mechanisms to produce seizures. Peripheral muscarinic receptors may play a specific role in lethality caused by PB + DEET.
 ...
PMID:Anticonvulsant-resistant seizures following pyridostigmine bromide (PB) and N,N-diethyl-m-toluamide (DEET). 1041 76

To investigate nitric oxide production in the brain of the EL mouse, an inbred mutant strain of the ddY mouse that is susceptible to convulsive seizures, we measured whole brain nitric oxide metabolites, and counted the number of nitric oxide-producing cells in the parietal cortex and striatum. Nitric oxide metabolites in the brain and serum were determined by measuring levels of nitrite plus nitrate. Nitric oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. Levels of nitrite plus nitrate in the whole brain were significantly lower than those of the control mice, although levels of nitrite plus nitrate in the serum did not differ between groups. There were significantly fewer NADPH-diaphorase-positive cells in the parietal cortex and striatum of the EL mouse compared to the ddY controls. These results suggest that lower nitric oxide production in the brain may be related to the susceptibility of the EL mouse to convulsive seizures.
 ...
PMID:Nitric oxide production is decreased in the brain of the seizure susceptible EL mouse. 1058 20

This study was undertaken to elucidate the anticonvulsive effects of zonisamide (ZNS: 25, 50, and 75 mg/kg, intraperitoneal [i.p.]), which was coadministered with valproic acid (VPA: 25, 50, and 100 mg/kg, i.p.), or phenytoin (PHT: 10, 25, and 50 mg/kg, i.p.) to ZNS concentration, nitric oxide metabolites (NOx levels), and monoamines in the brain of the EL mouse, a strain highly susceptible to seizures. NOx levels were obtained from measuring of combined level of nitrite plus nitrate. Coadministration of ZNS with VPA or PHT suppressed convulsive seizures more effectively than with treatment of ZNS alone. Both serum and brain concentrations of ZNS tended to increase as the dose of VPA or PHT was increased. While coadministrations of ZNS (75 mg/kg) and VPA or PHT at any dose did not change brain and serum NOx levels, those altered brain monoamine contents. These results suggested that anticonvulsive effect of coadministrations of ZNS and VPA or PHT were caused by changes of monoamines rather than changes of NO metabolites.
 ...
PMID:Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice. 1104 98

We evaluated age-related changes in nitric oxide (NO) production in the brains of EL mice, a strain highly susceptible to seizures. A group of EL(s) mice were tossed up weekly to induce convulsive seizures, while in a nonstimulated EL(ns) group induction of convulsive seizures was avoided. Brain levels of nitrite plus nitrate (NOx) in EL(ns) mice were significantly higher than in nonstimulated mice at 10 days, and also higher than levels at 15 and 50 weeks in either EL(s) or EL(ns) mice. A significantly higher number of NO-producing cells were demonstrated in the hippocampus and parietal cortex by staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase in EL(s) mice at the ages of 15 and 50 weeks than in EL(ns) mice at the age of 6 weeks. In EL(ns) mice, significantly fewer neurons showed NADPH-diaphorase staining in the hippocampus, striatum and parietal cortex at the age of 50 weeks than at 6 weeks. The present results suggest that whole-brain NOx levels in EL(ns) and EL(s) mice and numbers of NADPH-diaphorase-positive neurons in EL(ns) mice decreased with aging, while increasing of numbers of such neurons in EL(s) mice were assumed to develop in compensation for reduction in whole-brain NOx levels.
 ...
PMID:Age-related alterations of nitric oxide production in the brains of seizure-susceptible EL mice. 1111 84

Epilepsy and catalepsy were not clearly separated in the minds of people in the early 19th century, and catalepsy may have been used as a diagnostic euphemism for epilepsy. Tennyson, in "The Princess" describes, under the diagnosis of catalepsy, probable temporal lobe epileptic dreamy states with derealization which serve as a metaphor of sexual and moral ambivalence, the poem's central theme. It seems that Tennyson knew such seizures from his own father who had been given a diagnosis of catalepsy. Poe gave his Berenice in the novella of the same title a diagnosis of epilepsy as a reason for a premature burial. However, there was a good deal of unlikelyhood in this, and when he came to this theme in "The Fall of the House of Usher" and in "The Premature Burial" he chose instead a diagnosis of catalepsy which fitted better with the plot. The fits of the title character in George Eliot's Silas Marner, diagnosed as catalepsy, would today rather be seen as epileptic twilight states. It would seem that this author drew from contemporary dictionary descriptions which described conditions similar to Marner's fits under the heading of catalepsy. In Eliot's "legend with a realistic treatment", the twilight states are a central factor in the plot and explain Marner's reclusion and passivity. In Poor Miss Finch by English realist Wilkie Collins, the post-traumatic seizures of Oscar, one of the main characters, their cause, their treatment with silver nitrate, and the subsequent discoloration of his skin are central supporting elements of a perfectly constructed plot. Collins gives an exact description of a right versive seizure with secondary generalisation, and how to deal with it. In none of these works seizures are seen in a negative light. They rather evoke reactions of sympathy and support.
 ...
PMID:Epilepsy and catalepsy in Anglo-American literature between romanticism and realism: Tennyson, Poe, Eliot and Collins. 1123 70

Shaking behavior, so-called wet dog shakes (WDS), in rats is characteristic behavior indicating morphine abstinence in morphine-dependence and central excitation in relation to seizures elicited by chemicals or electrical stimulation. We have found that paraquat (PQ), a nonselective herbicide, administered systemically to rats induces WDS in a dose-dependent manner. PQ-induced WDS are suppressed by nitric oxide (NO) synthase (NOS) inhibitors, but this suppression is not reversed by an NO precursor, L-arginine (L-Arg). The present study was performed to determine whether the NO system is associated with PQ-induced WDS in rats. A time-course study on the frequency of WDS for each 30-min period up to 120 min after PQ administration (70 mg/kg, s.c.) revealed that significant induction of WDS occurred during the first and second 30-min periods, that is within 60 min of PQ administration. A nonselective NOS inhibitor, Nomega-nitro-L-arginine (L-NA; 30 mg/kg, i.p.), reduced the frequency of the PQ-induced WDS during both of these periods, but the reduced frequency was not reversed by L-Arg (500 mg/kg, i.p.) in either period. Significant induction of WDS occurred when PQ (50 nmol) was administered directly into the ventral or dorsal hippocampus, but not when administered into the amygdala or the caudate putamen, indicating that the hippocampus plays an important role in PQ-induced WDS. The WDS after the administration of PQ into the dorsal hippocampus was significantly suppressed by pretreatment with L-NA (30 mg/kg, i.p.). The extracellular levels of nitrite (NO2-) and nitrate (NO3-), the oxidative products of NO, in the dorsal hippocampus determined by in vivo microdialysis, were stimulated after systemic PQ administration (70 mg/kg, s.c.) in urethane-anesthetized rats. The increases in extracellular NO2- and NO3- were inhibited by L-NA (30 mg/kg, i.p.), and this inhibition was partly reversed by L-Arg (500 mg/kg, i.p.). The increases in extracellular NO2- and NO3- in the dorsal hippocampus appeared 60 min after PQ administration, when the WDS had occurred and disappeared. These findings suggest that NO production in the hippocampus plays a minor role in PQ-induced WDS in rats and that the suppression of PQ-induced WDS by NOS inhibitors might be mediated though complex mechanisms in the brain.
 ...
PMID:No parallel relationship between nitric oxide production and wet dog shakes susceptible to nitric oxide synthase inhibitors following systemic administration of paraquat in rats. 1130 80

The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.
 ...
PMID:Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide. 1144 80

To investigate changes of nitric oxide (NO) productions and zonisamide (ZNS) concentrations in the brain of seizure-susceptible EL mice given caffeine orally, mice were given caffeine (600 microg/mL) solution ad libitum as a drinking fluid for 1-3 weeks. Nitric oxide production in the brain was determined by measuring levels of nitrite plus nitrate (NOx). The brain NOx levels of mice treated with caffeine for 3 weeks were significantly higher than the control. Seizures in mice treated with caffeine for 2 and 3 weeks were not suppressed by ZNS at a dose of 75 mg/kg. Serum ZNS concentrations of mice with caffeine intake for 1-3 weeks were higher than in untreated mice. Conversely, brain ZNS concentrations of mice with caffeine intake for the same periods were significantly lower than in untreated mice. These results suggested that caffeine influenced brain NO production and ZNS concentrations in the seizure susceptibility of EL mice.
 ...
PMID:Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizure-susceptible EL mice. 1144 81

Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p<0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p<0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD.
 ...
PMID:IFN-gamma is effective in reducing infections in the mouse model of chronic granulomatous disease (CGD). 1155 34

The progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is a pediatric disorder of unknown origin, characterized by a combination of postnatally progressive encephalopathy, hypsarrhythmia, and optic atrophy. The pathological findings are early progressive atrophy of the cerebellum, brainstem, and optic nerves. Nitric acid (NO) has recently been implicated in the mechanisms of seizure activity and neurodegeneration, which are both very active in the PEHO syndrome. However, recent studies have provided evidence that insulin-like growth factor 1 (IGF-1) may prevent the NO-mediated neuronal damage and is essential for the survival of the cerebellar granule cells. These cells will degenerate in the PEHO syndrome. In this study, we set out to test the hypothesis that NO production is activated in the PEHO syndrome and that NO production may be correlated with the reduced production of IGF-1 in the brain. Cerebrospinal fluid IGF-1 was determined with an RIA kit and NO metabolites by the Griess calorimetric method. In patients with the PEHO syndrome, as compared with controls, the levels of IGF-1 were reduced and the levels of nitrite/nitrate were markedly elevated. Defective production of IGF-1 probably reflects the underlying neurodegeneration and the increase in NO production probably reflects the seizure activity and/or neurodegeneration. These are the first biochemical abnormalities found in the PEHO syndrome and their study may lead to a better understanding of this devasting disease.
 ...
PMID:The PEHO syndrome. 1170 Dec 91


<< Previous 1 2 3 4 5 Next >>