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)

A longitudinal study to estimate the serum calcium, phosphate and alkaline phosphatase levels of 89 ambulatory epileptic children, aged between 3 years and 12 years, and having generalised tonic-clonic seizures, was carried out. None was on any form of medication for the treatment of seizures prior to presentation. Each patient received only phenobarbitone during the period of study. Serum levels of the biochemical parameters were determined at presentation, 6 months and 12 months, while serum phenobarbitone levels were estimated at 6 months and 12 months. Mean serum calcium, phosphate and alkaline phosphatase of the patients remained within the normal range. Using the paired 't' test, the differences in the levels of the parameters at the three measurements were not statistically significant (P > 0.05). Serum phenobarbitone levels remained within the therapeutic range during the period of study. Our results show that over a 12-month period, serum levels of calcium, phosphate, and alkaline phosphatase, remain normal in ambulant epileptic children treated with phenobarbitone.
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PMID:Serum calcium, phosphate and alkaline phosphate levels in epileptic children treated with phenobarbitone. 955 46

The GABAergic system has long been implicated in epilepsy with defects in GABA neurotransmission being linked to epilepsy in both experimental animal models and human syndromes (Olsen and Avoli, 1997). However, to date no human epileptic syndrome has been directly attributed to an altered GABAergic system. The observed defects in GABA neurotransmission in human epileptic syndromes may be the indirect result of a brain besieged by seizures. The use of animal models of epilepsy has sought to address these matters. The advent of gene targeting methodologies in mice now allows for a more direct assessment of GABA's involvement in epileptogenesis. To date several genes associated with the GABAergic system have been disrupted. These include the genes for glutamic acid decarboxylase, both the 65- and 67-kDa isoforms (GAD65 and GAD67), the tissue non-specific alkaline phosphatase gene (TNAP) and genes for the GABA(A) receptor subunits alpha6, beta3, gamma2, and delta (gabra6, gabrb3, gabrg2, and gabrd respectively). Gene disruptions of either GAD67 or gabrg2 result in neonatal lethality, while others, GAD65, TNAP, and gabrb3 exhibit increased mortality and spontaneous seizures. GABA receptor expression has been found to be both regionally and developmentally regulated. Thus in addition to their obvious role in controlling excitability in adult brain, a deficit in GABAergic function during development could be expected to elicit pleiotropic neurodevelopmental abnormalities perhaps including epilepsy. The GABA(A) receptor beta3 subunit gene, gabrb3/GABRB3 (mouse/human), is of particular interest because of its expression early in development and its possible role in the neurodevelopmental disorder Angelman syndrome. Individuals with this syndrome exhibit severe mental retardation and epilepsy. Mice with the gabrb3 gene disrupted likewise exhibit electroencephalograph (EEG) abnormalities, seizures, and behavioral characteristics typically associated with Angelman syndrome. These gabrb3 gene knockout mice provide direct evidence that a reduction of a specific subunit of the GABA(A) receptor system can result in epilepsy and support a GABAergic role in the pathophysiology of Angelman syndrome.
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PMID:GABA and epileptogenesis: comparing gabrb3 gene-deficient mice with Angelman syndrome in man. 1051 60

We describe efficient methods for using functional proteomics analysis to study signal transduction pathways in murine fibroblast L929 cells following stimulation with tumor necrosis factor (TNF)-alpha. After stimulation with TNF-alpha, cellular proteins of L929 cells were extracted with a lysis buffer containing 0.3% sodium dodecyl sulfate (SDS) for 10-30 min time intervals, and were separated by two-dimensional (2-D) electrophoresis followed by immunoblot analysis with anti-phosphotyrosine antibody and alkaline phosphatase-anti IgG antibody conjugate. To improve detection sensitivity by immunoblot analysis we used a chemifluorescent substrate for alkaline phosphatase. One hundred protein spots were detected in the TNF-alpha stimulated L929 cell extract by immunoblot analysis. The use of chemifluorescence allowed us to quantitate immunoblotted spots with fluoroscanner so that we were able to detect time-dependent changes of a number of immunoblotted spots. Protein spots on a silver-stained 2-D gel corresponding to those detected by immunoblot analysis were subjected to in-gel trypsin digestion- matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)-mass spectrometry analysis, respectively. Twenty-one proteins detected by immunoblot analysis were identified by MS-Fit database search analysis. Among them, the proteins that show time-dependent changes in staining intensity include vimentin, tubulin beta-chain, eukaryotic translation initiation factor 1A, chromatin assembly factor 1 (P48 subunit), probable protein disulfide isomerase P5, and several other proteins. Vimentin and tubulin beta-chain have been reported to be phosphorylated at tyrosine residues and involved in the signal transduction pathway induced by TNF-alpha. However, the other proteins have no previously known function in the signal transduction pathway. Thus, the methods used in this study seem to be suitable for the identification of time-dependent changes in many proteins that are involved in signal transduction. Usefulness of the method for comprehensive analysis of the proteins involved in signal transduction pathway and the limitations of the method are discussed.
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PMID:Matrix assisted laser desorption/ionization-time of flight-mass spectrometry analysis of proteins detected by anti-phosphotyrosine antibody on two-dimensional-gels of fibrolast cell lysates after tumor necrosis factor-alpha stimulation. 1087 Sep 74

Normal fetal and neonatal calcium homeostasis is dependent upon an adequate supply of calcium from maternal sources. Both maternal hypercalcemia and hypocalcemia can cause metabolic bone disease or disorders of calcium homeostasis in neonates. Maternal hypercalcemia can suppress fetal parathyroid function and cause neonatal hypocalcemia. Conversely, maternal hypocalcemia can stimulate fetal parathyroid tissue causing bone demineralization. We report two asymptomatic women, one with previously unrecognized hypoparathyroidism and the other with unrecognized familial benign hypercalcemia, who were diagnosed when their newborn infants presented with abnormalities of calcium metabolism. J.B. was born at 34 weeks' gestation with transient hyperbilirubinemia and thrombocytopenia. At 1 month of age he had severe bone demineralization, cortical irregularities, widening and cupping of the metaphyses, and lucent bands in the scapulae. The total serum calcium and phosphorus were normal with an ionized calcium of 5.4 mg/dL (4.6-5.4). His alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were all increased. P.B., mother of J.B., had no symptoms of hypocalcemia either prior to, or during this pregnancy. She had severe hypocalcemia and hyperphosphatemia, laboratory values typical of hypoparathyroidism. J.N. presented at 6 weeks of age with new onset of seizures and tetany secondary to severe hypocalcemia. The serum phosphorus, creatinine, alkaline phosphatase, and parathyroid hormone levels were normal. At 15 weeks of age his calcium was slightly elevated with a low fractional excretion of calcium. P.N., mother of J.N., had no symptoms of hypercalcemia either prior to, or during this pregnancy. Her serum calcium was 12.7 mg/dL and urine calcium was 66.5 mg/24 hr, with a low fractional excretion of calcium ranging from 0.0064 to 0.0073. P.N. has a brother who previously had parathyroid surgery. Both J.N. and P.N. meet the diagnostic criteria for familial benign hypercalcemia. These cases illustrate the important relationships between maternal serum calcium levels and neonatal calcium homeostasis. They emphasize the need to assess maternal calcium levels when infants are born with abnormal serum calcium levels or metabolic bone disease.
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PMID:Disorders of maternal calcium metabolism implicated by abnormal calcium metabolism in the neonate. 1087 87

The gastrointestinal tract of mammals secretes a phospholipid-rich membrane that is enriched in alkaline phosphatase (AP) and surfactant proteins (surfactant-like particle, SLP). The production of this particle is stimulated in the small intestine by fat feeding and in cultured cells in vitro by transfection with intestinal alkaline phosphatase (IAP). To test whether tissue non-specific alkaline phosphatase (TNAP) was a factor in stimulating surfactant-like particle production in stomach and colon (tissues expressing TNAP), mice lacking this enzyme were studied. Mice were harvested at 8 days of life, when body weight of homozygous animals (TNAP -/-) was about half that of congenic controls (TNAP +/+) or heterozygotes (TNAP +/-), but before seizures had begun. No difference in content of the major SLP protein (65 kDa) by Western blotting or immunocytochemistry was seen in stomach or colon of TNAP -/- vs. TNAP +/+ animals, but the content was only about half in the IAP-expressing small bowel. Transmission electron microscopy of the TNAP -/- small bowel showed large dilated lysosomes and residual bodies. Colonocytes and gastric surface epithelial cells from the same animals showed mitochondria containing homogeneous dense inclusions, consistent with neutral lipid. In the underweight homozygous animals, there was a decrease in the neuronal content of submucosal ganglia in the jejunum and ileum and of myenteric ganglia in the jejunum of TNAP -/- animals. These findings suggest that (1) TNAP is not important in maintaining surfactant-like particle content of tissues that express TNAP, (2) normal fat absorption is important in maintaining SLP content in the small intestine, and (3) TNAP is important in the maintenance of some intestinal structures, and perhaps their function.
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PMID:Effect of tissue non-specific alkaline phosphatase in maintenance of structure of murine colon and stomach. 1105 62

The aim of our study was to investigate amino acid and energy metabolism of pentylenetetrazol (PTZ)-kindled animals. Glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamyltransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined in the frontal cortex, cerebellum, hippocampus and pons-medulla regions of Hannover-Wistar rats. The rats were randomly divided into four experimental groups: (a) control; (b) rats which received a single PTZ injection in a subconvulsive dose of 40 mg/kg i.p.; (c) rats which received a single PTZ injection in a convulsive dose of 50 mg/kg i.p.; and (d) PTZ-kindled rats. Kindling increased ALP activity throughout the brain, elevated AST as well as LDH activity in the frontal cortex and hippocampus and decreased CK activity in the frontal cortex and cerebellum. Acute seizures of the same intensity did not induce these alterations. The observed effects therefore are obviously linked to the kindling phenomenon and not to seizure activity. Changes appeared mainly in the frontal cortex and hippocampus, i.e. brain areas believed to be directly involved in kindling.
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PMID:Altered activities of rat brain metabolic enzymes caused by pentylenetetrazol kindling and pentylenetetrazol--induced seizures. 1116 5

The tissue non-specific alkaline phosphatase (TNAP) knock-out mouse is a model of infantile hypophosphatasia displaying impaired bone mineralization, epileptic seizures, apnoea, abnormal apoptosis in the thymus, abnormal lumbar nerve roots, and postnatal death. Administration of vitamin B6 suppresses the epileptic seizures in TNAP-/- mice. This paper examines to what extent the diverse abnormalities seen in these mice are due to impaired utilization of vitamin B6, using two complementary approaches: administration of vitamin B6 to TNAP null mice and deprivation of vitamin B6 in wild-type and TNAP heterozygous mice. Administration of exogenous pyridoxal HCl delayed the onset of epileptic attacks and increased the life span of TNAP-/- mice. The episodes of apnoea ceased and the appearance of lumbar nerve roots improved, but hypomineralization and accumulation of osteoid continued to worsen with age. Control mice fed a vitamin B6-depleted diet developed epileptic seizures indistinguishable from those observed in TNAP-/- mice, abnormal apoptosis in the thymus, and thinning of the nerve roots, but showed no evidence of bone mineralization abnormalities. Depletion of vitamin B6 did not affect the ability of primary cultures of osteoblasts to deposit bone mineral in vitro. While abnormal metabolism of vitamin B6 explains many of the abnormalities in this mouse model of infantile hypophosphatasia, it is not the basis of the abnormal mineralization that characterizes this disease.
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PMID:Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnormalities, but not the impaired bone mineralization. 1116 25

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.
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PMID:Empirical monotherapy with meropenem in serious bacterial infections in children. 1182 8

The clinical and laboratory findings of 21 children with amitraz poisoning were evaluated retrospectively. Poisoning route, signs and symptoms of poisoning, duration of hospitalization and outcome were recorded. The mean age was 3.5 +/- 1.9 years and the ratio of males to females was 1.63. In all cases poisoning was via the oral route. The time from ingestion to onset of symptoms was 30-180 min. Drowsiness (100%) and loss of consciousness (100%) were the most common clinical findings, followed by vomiting (61.9%). Hypotension was observed in 66.7% of cases, bradycardia in 61.9%, respiratory depression in 42.9%, hypothermia in 9.3%, and 14.3% had generalized seizures responsive to diazepam. Hyperglycaemia and glycosuria were detected in 47.6% and 38.1% of cases, respectively. Minimally elevated transaminases and alkaline phosphatase levels were detected in 23.8% of cases. All patients recovered completely and were discharged within 1.0-5.2 days (mean, 2.1 +/- 1.1).
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PMID:Amitraz poisoning in children: retrospective analysis of 21 cases. 1202 30

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.
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PMID:Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn. 1202 40


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