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)

In humans, deficiency of the tissue non-specific alkaline phosphatase (TNAP) gene is associated with defective skeletal mineralization. In contrast, mice lacking TNAP generated by homologous recombination using embryonic stem (ES) cells have normal skeletal development. However, at approximately two weeks after birth, homozygous mutant mice develop seizures which are subsequently fatal. Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mutant seizure phenotype can be rescued by the administration of pyridoxal and a semi-solid diet. Rescued animals subsequently develop defective dentition. This study reveals essential physiological functions of TNAP in the mouse.
 ...
PMID:Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. 755 Mar 13

Previous investigations have indicated that soman-induced convulsions involve the inositol lipid signalling system. We previously reported that 10 min after the onset of seizures, inositol 1,4,5-triphosphate (IP3) build-up was coupled to activation of non-muscarinic receptor subtypes. In the present study, we demonstrate that (1) in addition to muscarinic receptors, histamine H1 subtypes and glutamate metabotropic receptors contribute to the first IP3 increase (first 10 min of seizures) and (2) the histamine H1 subtype and glutamate metabotropic receptors are also involved in the second step of inositol phosphate response (after 10 min of seizures). alpha 1-adrenoceptor and 5-HT2 receptors, known to be coupled to phosphoinositide turnover, did not participate in soman-induced IP3 response. Neurochemical interactions between cholinergic, histamine H1 and glutamate metabotropic systems, responsible of the phosphoinositide hydrolysis under soman are envisaged.
 ...
PMID:Involvement of non-muscarinic receptors in phosphoinositide signalling during soman-induced seizures. 762 3

We report three neonates with transient hypoparathyroidism with elevated parathyroid hormone (PTH) levels to clarify further the pathogenesis of late neonatal hypocalcemia and calcium homeostasis. Clinical signs were seizures starting at age of 10 and 11 days. The biochemical features were characterized by transient hypocalcemia and hyperphosphatemia due to a high transport maximum of the phosphate/glomerular filtration rate, despite high PTH levels. All had normal magnesium and calcidiol levels (at least 5 micrograms/l) for their age, and this precludes hypoparathyroidism due to low magnesium levels and hyperparathyroidism due to overt vitamin D deficiency. To diagnose pseudohypoparathyroidism type I, intravenous human PTH (1-34) infusions were performed; however, they showed brisk responses of plasma and/or urine cyclic AMP in response to the PTH infusion, but the phosphaturic response to the PTH was sluggish compared to the controls. All three showed an increase in serum alkaline phosphatase activity, suggesting PTH stimulation of osteoblasts. They were treated initially with calcium lactate or (1 alpha)-hydroxycalciol/calcitriol. Their hypoparathyroid condition, however, was transient; they maintained normal serum calcium and PTH levels without medication before the age of 6 months. The etiology, possibly intracellular signal transduction distal to cyclic AMP and/or distinct from adenylate cyclase in the kidney, is developmental and the condition was resolved completely within 6 months of age. We have termed this condition "transient pseudohypoparathyroidism of the neonate".
 ...
PMID:Transient pseudohypoparathyroidism of the neonate. 765 38

Cellular volume and potassium contents were determined in rat astrocytes from primary culture following suspension in isoosmotic (269 mOsm) and hypoosmotic (136 mOsm) phosphate-buffered saline (PBS) containing various potassium concentrations. Within 1 min of suspension in hypoosmotic PBS, cells swelled to 135% of their volume in isoosmotic PBS. This initial swelling was not altered by varying the potassium concentration of the hypoosmotic PBS. After suspension in hypoosmotic PBS containing 3.2 mM potassium, a regulatory volume decrease (RVD) was observed. Higher concentrations of potassium in hypoosmotic PBS inhibited RVD following osmotic swelling. Cells swollen in hypoosmotic PBS containing 50 mM potassium continued to swell for 7 min, reaching a volume of 141% of their initial isoosmotic volume. After 7 min, these cells demonstrated a subsequent decrease in volume. The swelling observed between 1-7 min after suspension in hypoosmotic PBS containing 50 mM potassium was not affected by 10 microM gadolinium, 1 mM quinine, 1 mM DIDS (4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM SITS (4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid), 1 mM furosemide, or 100 microM bumetanide. Normal RVD was obtained in hypoosmotic PBS containing 50 mM potassium, if chloride was replaced with gluconate (but not nitrate) to reduce the extracellular K.Cl product to that of hypoosmotic PBS containing 3.2 mM potassium. The volume decrease seen between 7-30 min after exposure to hypoosmotic PBS containing 50 mM potassium was blocked by 1 mM DIDS, 1 mM SITS, or 1 mM furosemide. Cellular potassium content was elevated by approximately 60% after 7 min exposure to isoosmotic or hypoosmotic PBS containing 50 mM potassium. In hypoosmotic PBS, this increase in cellular potassium was reduced with replacement of chloride by gluconate, but not by nitrate. The results indicate that astrocytes swollen in PBS containing elevated potassium concentrations continue to swell, in part, by accumulation of potassium plus chloride mediated by an approach to Donnan equilibrium. Cotransport carriers or stretch-activated channels do not play a role in the enhanced swelling observed in hypoosmotic PBS containing 50 mM potassium. We suggest that a voltage-sensitive chloride channel mediates this continuation of cell swelling. This mechanism may be important in the persistent swelling of astrocytes observed in pathologic conditions such as trauma and seizures where extracellular potassium is elevated, or when other factors are present which may cause astroglial depolarization.
 ...
PMID:Hypoosmotic volume regulation of astrocytes in elevated extracellular potassium. 774 27

Glutamate decarboxylase (EC 4.1.1.15, GAD) activity was studied in the brain of 12-day-old and adult rats treated with 3-mercaptopropionic acid (3-MPA), an inhibitor of GAD competitive with glutamate. Control GAD activity in the brains of immature animals (91.8 +/- 18.2 nmol/h/mg of protein) was lower than that of the adult rats (228 +/- 37.5 nmol/h/mg of protein). Brain GAD inhibition in adult rats was 58% at the onset of seizures (9 min on the average after administration of 70 mg 3-MPA/kg). At the same time, 3-MPA-treated young rats exhibited 76% inhibition of GAD despite the fact that at 9 min these animals were not yet having seizures. At the onset of seizures (19 min after 3-MPA on the average) their GAD activity remained at the same level. The difference between the groups was not related to the presence of the coenzyme pyridoxal-5'-phosphate in the enzyme assay. The inhibition of GAD by 3-MPA in vitro in the immature and adult brains was similar (Ki at 5.1 microM and 4.8 microM concentrations of 3-MPA, respectively). Identical values were found for Km of GAD (at 4.5 mM concentration of L-glutamate). Calculations based on the results suggest that 3-MPA enters the immature brain more easily than the brain of the adult animals. While GAD inhibition by 3-MPA is the primary cause of seizures, their onset is influenced by other factors, in which the immature brain differs from the adult one and which may include less sensitivity to GABA decrease due to relative overactivity of the GABA system.
 ...
PMID:Differences between immature and adult rats in brain glutamate decarboxylase inhibition by 3-mercaptopropionic acid. 779 89

An abnormality in the pyridoxal-5'-phosphate (PLP) dependent enzyme, glutamic acid decarboxylase (GAD), which synthesizes gamma-aminobutyric acid (GABA), may underlie the epileptic syndrome of pyridoxine-dependent seizures. GABA synthesis by skin fibroblasts from an infant with pyridoxine-dependent seizures, and from five controls, was measured. PLP independent GAD activity was similar in control and patient fibroblasts, whereas the patient's PLP dependent GAD activity was reduced compared with controls. These findings support the hypothesis for the expression of this familial disease.
 ...
PMID:Reduced GABA synthesis in pyridoxine-dependent seizures. 791 Feb 33

Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high intensity sound stimulation (110.3 dB). R rats usually do not respond with any convulsive behavior to sound stimulation, whereas S animals develop a complex wild running sequence plus tonic-clonic seizure patterns after sound stimulation. Thus, R rats were injected with phosphate buffer (PB; 0.2 microliter) or N-methyl-D-aspartate (NMDA) in three different doses (2.0 micrograms, 2.5 micrograms and 3.0 micrograms/0.2 microliter) into central ventral or cortical dorsal inferior colliculus (IC) nuclei. Dose-response curves were evaluated by means of an ethological method in which behavioral sequences typical of S and R animals were quantitated. Animals displayed more severe spontaneous audiogenic-like seizures with the dose of 2.5 micrograms/0.2 microliter NMDA, which were potentiated by the acoustic stimulus. Significant differences were apparent between central and cortical nuclei and more severe seizures were observed in IC cortical microinjected animals. These audiogenic seizures were blocked with microinjections of 2-amino-7-phosphono-heptanoate (AP7) applied just before 2.5 micrograms NMDA microinjections into central or cortical nuclei. In S rats, AP7 totally blocked AS when microinjected into the central IC and partially, but significantly, blocked AS when applied into the cortical IC nucleus. In the last case, wild running was still present in 100% of the animals after AP7 treatment. These data may suggest an NMDA-dependent differential participation of IC subnuclei in the development of AS.
 ...
PMID:NMDA-dependent audiogenic seizures are differentially regulated by inferior colliculus subnuclei. 791 31

Although deficient inhibitory action of GABAergic neurons is frequently implicated in the pathogenesis of epileptic seizures, their exact contribution to the epileptogenicity is still controversial. In the present study, we investigated the effects of GABAergic action on kainic acid (KA)-induced hippocampal seizure in rats with or without hippocampal sclerosis (HS). HS was produced by pretreatment of KA (12 mg/kg i.p.) 3 weeks prior to induction of acute KA seizure (8 mg/kg i.p.). After development of epileptiform activity in the hippocampus, either muscimol (50 ng/microliters, 1.0 microliter) or vehicle (phosphate buffer solution, 1.0 microliter) was applied locally in the left dorsal hippocampus through a cannula and electrobehavioral observation was performed continuously for 6 h. The seizures were divided into four stages according to their severity. 7 days after the induction of acute seizure, the rats were sacrificed and subjected to histological examinations. In the rats without HS, muscimol reduced the seizure severity as well as neuronal damage, whereas muscimol facilitated the severity of both indicators in the presence of HS. Muscimol accelerated the propagation of epileptiform activity and the onset of more advanced seizure stages regardless of presence or absence of HS. Our study suggest that the GABAa function has dual effects on the final severity of KA-induced seizure depending on the presence or absence of HS and that it accelerates the rate of seizure development in either condition. The altered GABAa function in the presence of HS would probably modify seizure activity.
 ...
PMID:Altered GABAergic effects on kainic acid-induced seizures in the presence of hippocampal sclerosis in rats. 798 57

The dynamic effects of the non-competitive NMDA receptor antagonist, MK-801 on brain metabolism were investigated over 105 minutes in unanesthetized rats by proton and phosphorus NMR spectroscopy. MK-801 (0.5 and 5 mg/kg, i.p) induced no changes in intracellular pH, and in phosphocreatine, ATP, and inorganic phosphate levels, indicating that the drug preserved energy and intracellular pH homeostasis. There were transient increases in lactate after both doses of MK-801, suggesting early activation of glycolysis, which was not immediately matched by enhanced oxidative metabolism or by enhanced blood flow. Thereafter, lactate control level was not restored after 0.5 mg/kg whereas it was restored after 5 mg/kg in spite of a sustained metabolic activation. The low dose of MK-801 also caused a continuous decrease in cerebral aspartate level (-38%) which is thought to match the enhanced energy demand, whereas the high dose caused shorter and smaller changes. The intracerebral glucose level rose after MK-801 injection, indicating that brain tissue had an adequate or even excessive supply of glucose. Glucose time course seemed to closely match the changes in blood flow elicited by MK-801. This is the first study giving the metabolic pattern of a pharmacological activation. We demonstrate an excess of glycolysis over oxidative metabolism in the early time similar to that following physiological and pathophysiological states such as photic stimulation and seizures. The difference between the effects of the two doses of MK-801 suggests that the adjustment of cerebral metabolism to MK-801 activation is faster and greater with the high dose than with the low dose.
 ...
PMID:Cerebral metabolic changes induced by MK-801: a 1D (phosphorus and proton) and 2D (proton) in vivo NMR spectroscopy study. 803 9

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 +/- 0.05 vs 7.00 +/- 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 +/- 6.0 vs 23.0 +/- 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.
 ...
PMID:Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy. 810 2


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