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)

Seizure disorders frequently occur early in life. Seizures are classified as reactive, symptomatic, or idiopathic depending on whether their cause can be identified. Reactive seizures are the result of acute environmental perturbations. Early in life, many stressors can produce seizures and the ultimate outcome may depend on the particular precipitating factor and its intensity. Febrile convulsions are the most common reactive seizures, although they must be differentiated from symptomatic seizures precipitated by fever. Symptomatic seizures are often associated with varying degrees of central nervous system (CNS) insults, including congenital malformations and metabolic storage diseases of the gray matter. These seizures may have age-specific characteristics and may at times be difficult to treat with conventional antiepileptic treatments. To develop a better understanding of the pathophysiology of seizures early in life, we have extensively used animal models of epilepsy. In this chapter, we report our findings with a rat model of developmental cortical dysplasias produced by intrauterine injections of methylazoxymethanol acetate. These rats are more susceptible to kainic acid, flurothyl, and hyperthermic seizures than normal rats. Rats with severe cortical dysplasia are most susceptible to seizures. We have also studied the mechanisms involved in the control of seizures during development because status epilepticus is more prevalent in infants than in adults. Our data suggest that the substantia nigra may play a crucial role in status epilepticus as a function of age. In the adult substantia nigra two regions mediate opposing effects on seizures following infusions of gamma-aminobutyric acid type A (GABAA) agents. One region is located in the anterior substantia nigra, and muscimol infusions in this region mediate anticonvulsant effects. The second region is in the posterior substantia nigra, and here muscimol infusions produce proconvulsant effects. In situ hybridization data demonstrate that, at the cellular level, neurons in the two substantia nigra regions differ in the amount of hybridization grains for GABAA receptor alpha 1 and gamma 2L subunit mRNAs. In developing male rats, only the "proconvulsant" region is present up to the age of 21 days. The transition from the immature to mature substantia nigra mediated seizure control occurs between age 25 and 30 days. The identification of age-dependent functional networks involved in the containment of seizures may lead to possible new pharmacologic strategies to control seizures, thus aiding the development of age-appropriate treatments of seizure disorders.
 ...
PMID:Age-dependent vulnerability to seizures. 1051 12

Limbic seizure was induced in rats by intraperitoneal injection of the glutamate receptor agonist kainic acid. After 14 days [1-13C]glucose and [1,2-13C]acetate were injected subcutaneously and the rats killed 15 min later. Analysis of brain extracts was performed using 13C-magnetic resonance spectroscopy and high performance liquid chromatography. No significant differences between the two groups of rats were found for label concentration in blood or total metabolite tissue levels. Only astrocytes are able to utilize acetate as a substrate, whereas glucose is thought to be metabolized predominantly in the neuronal tricarboxylic acid cycle. Thus information about neuronal and astrocytic metabolism could be obtained in the same animal. A significant increase in label derived from [1-13C]glucose was observed in metabolites such as glutamate, gamma-aminobutyric acid, aspartate, and succinate (all of which are mainly labelled in neurones). The increased labelling of glutamine in epileptic rats might be due to transfer of labelled glutamate from neurones to astrocytes. Astrocytic metabolism of acetate and transfer of glutamine to neurones were not affected. The results suggest that increased neuronal activity 2 weeks following epileptic seizures produces increased amino acid turnover in neurones. Changes in astrocytic metabolism were not detected.
 ...
PMID:Amino acid neurotransmitter metabolism in neurones and glia following kainate injection in rats. 1068 56

Cortical disorganization represents one of the major clinical findings in many children with medically intractable epilepsy. To study the relationship between seizure propensity and abnormal cortical structure, we have begun to characterize an animal model exhibiting aberrant neuronal clusters (heterotopia) and disruption of cortical lamination. In this model, exposing rats in utero to the DNA methylating agent methylazoxymethanol acetate (MAM; embryonic day 15) disrupts the sequence of normal brain development. In MAM-exposed rats, cells in hippocampal heterotopia exhibit neuronal morphology and do not stain with immunohistochemical markers for glia. In hippocampal slices from MAM-exposed animals, extracellular field recordings within heterotopia suggest that these dysplastic cell clusters make synaptic connections locally (i.e. within the CA1 hippocampal subregion) and also make aberrant synaptic contact with neocortical cells. Slice perfusion with bicuculline or 4-aminopyridine leads to epileptiform activity in dysplastic cell clusters that can occur independent of input from CA3. Taken together, our findings suggest that neurons within regions of abnormal hippocampal organization are capable of independent epileptiform activity generation, and can project abnormal discharge to a broad area of neocortex, as well as hippocampus.
 ...
PMID:Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero. 1075 97

Acidophilia is one of the hallmarks of acute neuronal damage and death in brain ischemia, excitotoxic and traumatic lesions and epileptic seizures. We here describe a novel and simple method for visualizing acidophilic neurons on paraffin sections, using vanadium acid fuchsin (VAF) staining and toluidine blue or hematoxylin counterstaining. Paraffin sections of the brain fixed in ethanol-formalin-acetic acid mixture are stained in 0.1% acid fuchsin containing 0.125% of ammonium metavanadate and 1% of glacial acetic acid, differentiated if overstained in 0.01% of borax solution, and counterstained with 0.05-0.025% of toluidine blue in acetate buffer (pH 3.3) or Gill's II hematoxylin. The sections are dehydrated, cleared in xylene and mounted in Canada balsam or any synthetic mounting media for light microscopy. VAF combined with toluidine blue or hematoxylin results in highly selective and reproducible color contrast staining of acidophilic neurons as well as glial nuclei and hyperchromatic neurons. As a progressive method, acid fuchsin staining usually does not require differentiation. The red acidophilic neurons are clearly visible on the background of non-damaged cells, which significantly facilitates the identification, and localization of damaged neurons, even at low magnification under the light microscope.
 ...
PMID:Improved selective, simple, and contrast staining of acidophilic neurons with vanadium acid fuchsin. 1077 32

Status epilepticus causes significant morbidity and mortality. A case of generalized status epilepticus followed by massive pulmonary aspiration, acute respiratory failure and transient central diabetes insipidus is presented. Seizures were promptly controlled, but the patient required mechanical ventilation and correction of polyuria with desmopressin acetate. During hospitalization mental status improved, diabetes insipidus spontaneously remitted and he was discharged without neurologic sequelae. The clinical and pathophysiological features of this case are discussed.
 ...
PMID:Generalized status epilepticus associated with massive pulmonary aspiration and transient central diabetes insipidus: case report. 1101 32

We report a case of a 13-year-old female with atypical absence seizures induced by prolonged administration of long-acting leuprolide acetate (LA). This patient had brain involvement resulting from chemotherapy and radiotherapy for a medulloblastoma. At 13 years of age, administration of long-acting LA was started. After the third dose of long-acting LA, atypical absence seizures appeared. After discontinuing long-acting LA, the seizures stopped without administration of any antiepileptic drugs. However, 2 years, 6 months later, the same seizures again appeared. On the basis of the findings of endocrinologic investigations and the reported data of pharmacokinetics of LA, we speculate that her seizures were induced by LA and that the seizures were associated with the presence of brain damage in the patient. Care should therefore be taken when using long-acting LA or other gonadotropin-releasing hormone analogues for pediatric patients with diffuse brain damage.
 ...
PMID:A case of atypical absence seizures induced by leuprolide acetate. 1103 92

Bone loss leading to osteoporosis is common after the menopause and in the elderly but uncommon in normal young adults without predisposing factors. The risk factors usually associated with osteoporosis include a family history of osteoporosis or fractures, aging, prior diseases, sedentary lifestyle, low calcium intake, hypogonadism, vitamin D deficiency, smoking, and excessive alcohol consumption. However, the issue of drugs has to be considered in 'normal' individuals who present with osteoporosis or bone loss without predisposing genetic or other environmental factors. The list of drugs is extensive and includes, amongst others, glucocorticoids, thyroid hormone (excess), alcohol, medroxyprogesterone acetate, luteinizing hormone-releasing hormone agonists, anti-seizure medications, cyclosporine A, aluminium, lithium, and exchange resins. This paper reviews the pathophysiology and mechanisms of drug-induced bone loss, which includes osteoporosis and osteomalacia, and treatment concepts. Undoubtedly, physician awareness, appropriate investigation, careful prescribing, monitoring, and proper therapy for this eminently preventable side effect can preserve bone in the patients receiving bone-losing drugs.
 ...
PMID:Drug-induced bone loss. 1109 67

The death of a 36-year-old alcoholic man who died after developing seizure activity while being treated with tramadol, as well as with venlafaxine, trazodone, and quetiapine, all of which interact with the neurotransmitter serotonin, is reported. The decedent, who had a history of chronic back pain, alcoholism, depression, mild hypertensive cardiovascular disease, and gastritis, had just been discharged from the hospital after 4 days of alcohol detoxification treatment. During the admission, no withdrawal seizures were noted. The morning after discharge, a witness observed the decedent exhibiting seizure activity and then collapsing. An autopsy was performed approximately 6 hours after death, and the anatomic findings were consistent with seizure activity and collapse, which included biting injuries of the tongue and soft-tissue injuries of the face. Toxicologic analysis identified tramadol, venlafaxine, promethazine, and acetaminophen in the urine; tramadol (0.70 mg/L) and venlafaxine (0.30 mg/L) in the heart blood, and 0.10 mg of tramadol in 40 ml of submitted stomach contents. No metabolites, such as acetate, acetone, lactate, and pyruvate, were found in the specimens that would be characteristically found in a person with alcohol withdrawal syndrome. The threshold for seizures is lowered by tramadol. In addition, the risk for seizure is enhanced by the concomitant use of tramadol with selective serotonin reuptake inhibitors or neuroleptics, and its use in patients with a recognized risk for seizures, i.e., alcohol withdrawal. The cause of death in this individual was seizure activity complicating therapy for back pain, depression, and alcohol withdrawal syndrome. The data in Adverse Event Reporting System of the Food and Drug Administration from November 1, 1997 to September 8, 1999 was reviewed along with a MEDLINE search from 1966 to the present. This case appears to be the first reported death caused by seizure activity in a patient taking tramadol in combination with drugs that affect serotonin.
 ...
PMID:Lethal combination of tramadol and multiple drugs affecting serotonin. 1111

Glutamatergic neurotransmission, particularly of the NMDA receptor type, has been implicated in the excitotoxic response to several external and internal stimuli. In the present investigation, we report that S-methyl-N,N-diethylthiocarbamate sulfoxide (DETC-MeSO) selectively and specifically blocks the NMDA receptor subtype of the glutamate receptors, and attenuates glutamate-induced neurotoxicity in rat-cultured primary neurons. Other major ionotropic glutamate receptor subtypes, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate, were insensitive to DETC-MeSO both in vitro and in vivo. Disulfiram, the parent compound of DETC-MeSO, also inhibits glutamate receptors partially in vivo; however, it fails to inhibit glutamate receptors in mice pretreated with N-butyl imidazole, a cytochrome P450 enzyme inhibitor, implicating the need for bioactivation of disulfiram to be an effective antagonist. We showed that glutamate-induced increase in (45)Ca2+ was attenuated in rat-cultured primary neurons following pretreatment with DETC-MeSO. The Ca2+ influx into primary neurons, studied by confocal microscopy of the fluorescent Ca2+ dye fura-2, demonstrated a complete attenuation of NMDA-induced Ca2+ influx. Similarly, DETC-MeSO attenuated NMDA-induced (45)Ca2+ uptake. Glutamate-induced (45)Ca2+ uptake and Ca2+ influx, however, were partially blocked by DETC-MeSO, and this is consistent with both in vitro and in vivo studies in which DETC-MeSO partially blocked mouse brain glutamate receptors. In addition, DETC-MeSO pretreatment effectively prevented seizures in mice induced either by NMDA, ammonium acetate, or ethanol-induced kindling seizures, all of which are believed to be mediated by NMDA receptors. These data demonstrate that DETC-MeSO produces the neuroprotective effect through antagonism of NMDA receptors in vivo.
 ...
PMID:S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effect against N-methyl-D-aspartate receptor-mediated neurotoxicity. 1117 83

A Federal appeals court has ruled that a strip-search of ten AIDS activists by U.S. marshals following a demonstration in 1989 was unlawful. In overturning a lower court ruling, the appeals court said the marshals' action violated the demonstrators' Fourth Amendment right to be free from unreasonable searches and seizures. ACT UP's Portland chapter organized picketing and a rally outside the offices of the Food and Drug Administration (FDA) in Portland. The event was nonviolent, and the protesters briefed police and the U.S. Attorney's Office in advance about the nature of the demonstration. Ten activists were taken into custody for creating a noisy disturbance in the hall outside the FDA offices. The marshals decided to strip-search the activists before booking them. The lawsuit charges that the procedures the marshals used were degrading and intrusive and without reasonable basis. The deputy who initiated the searches claimed he did so because he assumed one of the ten activists had slashed the van's tires and might have the knife secured in his or her clothing. The activists are entitled to damages from the U.S. government.
 ...
PMID:U.S. marshals held liable for strip-searching AIDS activists. 1136 1


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