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)

A female child suffering from intrauterine growth retardation was born by caesarean section at 32 weeks. In the immediate newborn period there was a metabolic acidosis but this resolved. Hypotonia, muscular weakness and poor respiratory effort were evident and the child died at 6 days of age. A previous male sibling had died at 3 months of age after similar symptoms with seizures and a dysmyelination disorder. Post-mortem examination of both children showed damage to the basal ganglia. Defects in the activities of the pyruvate dehydrogenase complex, cytochrome oxidase and succinate cytochrome c reductase were found in cultured skin fibroblasts. Similar defects were found in isolated muscle mitochondria but not in isolated liver mitochondria from the patient. Immunoblotting for cytochrome oxidase showed that the multienzyme complex was not assembled in muscle and skin fibroblast mitochondria, but was assembled in liver mitochondria. Similar results were obtained in cultured skin fibroblast mitochondria for complex I of the mitochondrial respiratory chain. This is the first occasion that multiple defects have been demonstrated both in tissue and in culture skin fibroblasts in mitochondrial respiratory chain complexes.
 ...
PMID:Fatal combined defects in mitochondrial multienzyme complexes in two siblings. 132 97

We report the clinical, electroencephalographic, neurophysiologic, and neuroimaging findings in eight children with infant-onset progressive myoclonus epilepsy, all of whom had muscle biopsies performed as as part of the diagnostic evaluation. Each child had myoclonic seizures, generalized tonic-clonic seizures, and neurologic regression or marked developmental delay. Four children died before 3 years of age. Electroencephalograms in seven children showed an abnormally slow background with bilateral multifocal paroxysmal discharges but no burst suppression pattern or photoparoxysmal response. Muscle biopsy specimens were submitted for histopathology and respiratory-chain enzyme studies. Nonspecific abnormalities on light microscopy or electron microscopy were found in seven samples, including increased subsarcolemmal deposits of mitochondria or morphologic mitochondrial changes, but no ragged-red fibers were seen. Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway. This study has shown that infant-onset progressive myoclonus epilepsy can be distinguished from other myoclonic epilepsy syndromes of infancy by clinical and electrographic features. Furthermore, respiratory-chain enzyme defects are a relatively common cause of infant-onset progressive myoclonus epilepsy. The absence of ragged-red fibers on muscle histopathology does not preclude a mitochondrial enzyme abnormality.
 ...
PMID:Infant-onset progressive myoclonus epilepsy. 2198 53

We report two siblings with a mitochondrial encephalomyopathy. The syndrome was characterized by ataxia, intellectual impairment, myoclonic jerks, rare seizures, and small stature. Muscle biopsy specimens showed abnormal accumulations of mitochondria and lipid droplets. Biochemical studies on muscle demonstrated decreased succinate-cytochrome c reductase activity in the mitochondrial respiratory chain.
 ...
PMID:Mitochondrial encephalomyopathy with decreased succinate-cytochrome c reductase activity. 631 58

Purposes of this work were to develop an enzyme system as an in vitro model of the NADPH-dependent component of nitric oxide synthase (NOS) and examine the plausible down-regulation of this system and brain NOS by copper (II)2(3,5-diisopropylsalicylate)4[Cu(II)2(3,5-DIPS)4] as a mechanism accounting for its analgesic, anticonvulsant, and other pharmacological activities. Porcine heart diaphorase (PHD) was found to oxidize 114 microM NADPH with the corresponding reduction of an equivalent amount of 2,6-dichlorophenolindophenol (DCPIP). Addition of Cu(II)2(3,5-DIPS)4 to the reaction mixture decreased the reduction of DCPIP without substantially affecting the oxidation of NADPH. The IC50 for Cu(II)2(3,5-DIPS)4 in inhibiting the reduction of DCPIP was 1.5 microM. Mechanistically, this inhibition of DCPIP reduction was found to be due to the ability of Cu(II)2(3,5-DIPS)4 to serve as a catalytic electron acceptor for reduced PHD, which was enhanced by the presence of a large concentration of DCPIP and inhibited by a large concentration of NADPH. Oxidation of NADPH by PHD in the absence of DCPIP was linearly related to the concentration of Cu(II)2(3,5-DIPS)4 through the concentration range of 5-25 microM Cu(II)2(3,5-DIPS)4 with 50% recovery of NADPH oxidation by PHD at a concentration of 16 microM Cu(II)2(3,5-DIPS)4. Whole rat brain tissue sections incubated in medium containing an NADPH-generating system and nitroblue tetrazolium chloride (NBT) were less intensely stained when Cu(II)2(3,5-DIPS)4 was added to the medium. It is concluded that Cu(II)2(3,5-DIPS)4 serves as an electron acceptor in down-regulating PHD reduction of DCPIP and in down-regulating NOS in brain tissue sections. A decrease in NO synthesis in animal models of seizure, pain, and other disease states with Cu(II)2(3,5-DIPS)4 may account for the anticonvulsant, analgesic, and other pharmacological activities of this complex.
 ...
PMID:Down-regulation of NADPH-diaphorase (nitric oxide synthase) may account for the pharmacological activities of Cu(II)2 (3,5-diisopropylsalicylate)4. 942 75

Blockade of nitric oxide synthase (NOS) activity in the developing nervous system may protect the brain from hypoxic-ischemic insult. We determined the efficacy in 7 day old rat pups of systemically administered cysteamine in reducing neuronal NOS and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivities and protection of the brain from an hypoxic-ischemic insult. Cysteamine reversibly reduced NOS immunoreactivity at 2 h after an intraperitoneal injection of 200 mg/kg. NADPH-diaphorase histochemical reactivity was reduced after 300 mg/kg but all animals had generalized seizures and succumbed to the hypoxia-ischemia. At lower doses, despite the blockade of NOS immunoreactivity, there was no difference in the number of injured animals compared to controls. These results demonstrate that NOS immunoreactivity does not represent all of NADPH-diaphorase reactivity and that blockade of this activity with cysteamine is not protective.
 ...
PMID:Cysteamine eliminates nitric oxide synthase activity but is not protective to the hypoxic-ischemic neonatal rat brain. 884 8

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation.
 ...
PMID:Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse. 957 68

Generalized tonic-clonic seizures of brain stem origin in rats are associated with acute induction of neuronal Fos in several discrete regions of the brain. One particular site in the dorsal pons shows remarkable Fos induction following generalized tonic seizures induced by maximal electroshock in normal rats or by audiogenic stimulation in genetically epilepsy-prone rats (GEPRs). Although this area shows the most intense Fos induction of any brain area following generalized tonic seizures, its identity has been uncertain. Based on its general location, we hypothesized that this nucleus was either 1) a component of the pedunculopontine tegmentum nucleus-pars compacta (PPTn-pc) or 2) the superior lateral subnucleus of lateral parabrachial area (LPBsl). The present study used Fos-protein immunocytochemistry in combination with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, cholecystokinin (CCK) immunocytochemistry, and neuronal tract-tracing to determine the identity of this cluster of Fos-immunoreactive neurons in the dorsal pons. Following maximal electroshock seizure (MES), Fos labeling was compared to NADPH diaphorase staining (a marker for cholinergic neurons of the PPTn-pc); retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the ventromedial nucleus of the hypothalamus (VMH; to identify the LPBsl) or CCK immunoreactivity (also a marker for LPBsl neurons). Results showed this cluster of Fos immunoreactive (FI) neurons to be closely associated, but not overlapping, with the lateral and most caudal aspect of the PPTn-pc. Alternatively, WGA-HRP retrograde-labeled neurons corresponded precisely with the seizure-induced FI neurons. Additionally, the location of CCK immunoreactive neurons directly overlapped with the FI neurons, although they were not nearly as prevalent. These results demonstrate that the seizure-induced FI neurons in this area are neurons of the LPBsl and not cholinergic neurons of the PPTn-pc. This is the first report of seizure-induced Fos expression specifically localized to the superior lateral subnucleus of the lateral parabrachial area.
 ...
PMID:Expression of Fos in the superior lateral subdivision of the lateral parabrachial (LPBsl) area after generalized tonic seizures in rats. 982 Jul 33

The distribution and time course of changes of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positivity were studied in immature rats (12 and 25 days old) surviving motor status epilepticus (SE) induced by a high dose of pilocarpine. Motor SE characterized by continuous convulsions was interrupted after 2 h by an injection of clonazepam (0.5 mg/kg or 1 mg/kg in 12- and 25-day-old rats, respectively) in order to reduce mortality. Correlation between electroencephalographic and behavioral seizure activity was confirmed using animals with electrodes implanted bilaterally in the hippocampus and sensorimotor cortex. Brains were examined 2, 6, 13, and 21 days after motor SE using NADPH-diaphorase histochemistry. Two types of changes were found in both age groups: (a) decrease of NADPH-d positivity occurred in both neuropil and cell bodies in piriform, periamygdalar, and entorhinal cortices; and (b) NADPH-d positivity was induced in the cell bodies in the hippocampal fields CA1/2, CA3, and dentate gyrus. These changes were more intense in animals surviving SE at postnatal day 25 than in younger age group, and they peaked 2 days after SE. The changes observed after SE disappeared quickly in 12-day-old rat pups, where only moderate changes could be observed in piriform, periamygdalar, and entorhinal cortices 6 days after SE, whereas the changes in the histochemical positivity persisted in older animals even 21 days after SE.
 ...
PMID:Changes in NADPH-diaphorase positivity induced by status epilepticus in allocortical structures of the immature rat brain. 1021 Jan 66

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.
 ...
PMID:Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats. 1040 44

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


1 2 Next >>