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 52-year-old previously healthy woman was admitted to our hospital for status epilepticus in November 1999. She had not taken oral contraceptives. After treatment with intravenous diazepam and phenytoin, she did not develop seizures anymore. When she became alert, there was a mild left hemiparesis. Lumbar puncture showed an opening pressure of 145 mm H2O, and the cerebrospinal fluid was acellular. Cranial MR imaging demonstrated thrombosis of the superior sagittal sinus and fresh infarction in the right frontal lobe. Plasma fibrinogen, fibrin degradation product, and prothrombin fragment 1 + 2 levels were elevated. Proteins S and C activities and anti-thrombin III levels were within the normal range. Lupus anticoagulant and anti-cardiolipin antibody were negative. She was treated with continuous heparin infusion for ten days and with oral warfarin thereafter. Six months after the first admission, platelet count became more than 400 x 10(3)/microliter. In July 2002, she developed slowly progressive monoplegia of the left arm. Cranial MR imaging demonstrated patent superior sagittal sinus, fresh infarction in the right parietal lobe, and old small infarction in the right corona radiata. The patient was maintained on warfarin and 100 mg of aspirin thereafter. In September 2002, platelet count was 737 x 10(3)/microliter. Bone marrow examination showed increased megakaryopoiesis with normal erythroid and myeloid series and no chromosomal aberrations. Serum C-reactive protein and iron levels were in the normal range. An abdominal ultrasound demonstrated mild splenomegaly. Thus, we made a diagnosis of essential thrombocythemia (ET). ET causes thrombotic events in the course of the disease at a rate of 7% per year. Cerebral infarction is not uncommon, but occurrence of cerebral sinus thrombosis has been rarely reported. Recently, several cases have been reported in which cerebral infarction was the first manifestation of ET even with platelet counts lower than 600 x 10(3)/microliter. To our knowledge, there have been no reported cases of ET presenting with cerebral venous sinus thrombosis. Platelet count should be monitored in the patients with venous sinus thrombosis of undetermined etiology.
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PMID:[Superior sagittal sinus thrombosis as first manifestation of essential thrombocythemia]. 1519 36

Traumatic brain injury (TBI) is often complicated by the occurrence of seizures, which adversely affect clinical outcome. The risk of seizures increases to the extent that the injury is associated with sub-arachnoid hemorrhage and hematoma. A likely mechanism of seizure development post-TBI is decompartmentalization of iron from extravasated hemoglobin (Hb). It is well known that iron can catalyze formation of reactive oxygen species (ROS). Based on this proposed mechanism, a descriptive model of TBI-induced seizures, using intracortical injection of iron salts, was developed by Willmore. We have added modifications to enhance the quantifiability of seizure activity and have used the model to examine the therapeutic efficacy of lipoic acids (ROS-scavenging antioxidants). Male SD rats were pretreated with alpha-lipoic acid (ALA) and dihydrolipoic acid (DHLA) or appropriate vehicles. Under anesthesia, unilateral intracortical infusions of ferric chloride were performed stereotaxically. EEG was recorded via extradural electrodes. EEG was sampled for 10 s of every 60-s interval over a 24-h period following injection of ferric chloride. We measured the number of seconds of epileptiform discharges or seizure activity in every 10-s EEG sample during the 24 h. The EEGs of rats pretreated with ALA and DHLA exhibited 55% less seizure activity than vehicle-treated ferric chloride-injected animals, suggesting that lipoic acids may be of use in preventing or attenuating TBI-induced seizures.
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PMID:Lipoic acid pretreatment attenuates ferric chloride-induced seizures in the rat. 1524 49

Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin, and hemoglobin itself, are associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been demonstrated to be involved in the mechanism of seizures induced by iron ions in the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS are responsible for the induction for peroxidation of neural lipids, i.e., an injury of neuronal membranes, and also could induce disorders in the excitatory and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent the epileptogenic focus formation, or to attenuate seizure activities in the iron-injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate, adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic discharge in the iron-injected rat brain.
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PMID:Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies. 1547 32

Mitochondrial dysfunction has been implicated as a contributing factor in diverse acute and chronic neurological disorders. However, its role in the epilepsies has only recently emerged. Animal studies show that epileptic seizures result in free radical production and oxidative damage to cellular proteins, lipids, and DNA. Mitochondria contribute to the majority of seizure-induced free radical production. Seizure-induced mitochondrial superoxide production, consequent inactivation of susceptible iron-sulfur enzymes, e.g., aconitase, and resultant iron-mediated toxicity may mediate seizure-induced neuronal death. Epileptic seizures are a common feature of mitochondrial dysfunction associated with mitochondrial encephalopathies. Recent work suggests that chronic mitochondrial oxidative stress and resultant dysfunction can render the brain more susceptible to epileptic seizures. This review focuses on the emerging role of oxidative stress and mitochondrial dysfunction both as a consequence and as a cause of epileptic seizures.
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PMID:Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. 1554 15

Posttraumatic epileptic seizures have an incidence of about 10% in series of severe head injuries. Control of "early seizures", i.e. those occurring in the first week after injury, is mandatory. Attacks, especially if recurrent, may add secondary damage to the injured brain: intravenous phenythoin with therapeutic plasma level allows control of the attacks. Seizures occurring months or years after injury are called "late seizures": recurring "late seizures" make up the clinical syndrome of "posttraumatic epilepsy". "Prophylaxis" should mean that drug treatment, given for a more or less prolonged period of time, blocks permanently the ripening of the epileptogenic foci avoiding the occurrence of seizures. In animal "prophylaxis" by antiepileptic drugs seems efficacious in many experimental models including iron induced epilepsy which is considered a model of posttraumatic epilepsy and vice versa. In the human being "prophylaxis" has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but without success. During treatment period the occurrence of seizures is prevented but, after discontinuation of the drug, seizures occur just as in non treated patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in iron induced epilepsy, seems to be due to a cascade of events beginning with haemorrhage, haemolysis, iron or heme compound liberation, free radical formation, peroxidation and cell death. Experimentally free radical scavengers and antiperoxidants have marked prophylactic effect. Some of them (phosphate diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in clinical practice, but up to date there is no controlled study in human beings.
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PMID:Posttraumatic epilepsy with special emphasis on prophylaxis and prevention. 1598 23

The lack of evidence-based information in toxicology results in debate and differing recommendations on management issues. Gastric lavage is often utilized to remove toxins from the stomach but a clinical benefit of the procedure has not been definitively demonstrated. A selective approach is warranted in each patient, and gastric lavage can be considered in patients with life-threatening ingestions if it can be performed within 60 minutes of ingestion. Whole bowel irrigation is a method of GI decontamination utilizing isotonic electrolyte solution. Although safe, there is currently insufficient data to establish definite indications for use. This technique can be considered for potentially toxic ingestions of lithium, iron, and sustained-release or enteric-coated drugs. Multiple-dose activated charcoal has been used to enhance elimination of drugs already absorbed into the body but the optimum dose and frequency of administration is not established. Based on volunteer studies and limited clinical reports, multiple-dose activated charcoal may be considered in patients with life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. A variety of interventions in addition to hemodialysis have been proposed to enhance lithium elimination. Forced saline diuresis and diuretics are not indicated. Although studies suggest that sodium polystyrene sulfonate may enhance elimination of lithium, no beneficial effects on clinical outcomes have been demonstrated and potential complications include hypokalemia and hypernatremia. Blood alkalinization for cyclic antidepressant toxicity has become standard therapy. Alkalinization is most effective in treating significant cardiac toxicity. Sodium bicarbonate, rather than hyperventilation, should be used initially to alkalinize blood. The benefit of blood alkalinization in the treatment of hypotension and seizures is not established.
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PMID:Management issues in toxicology. 1608 58

The genetically programmed form of neuronal death known as apoptosis plays a role in many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease. Apoptosis is also responsible for neuronal death after traumatic brain and spinal cord injury, stroke, and seizures. The cognitive and behavioral consequences of all of these disorders can be devastating. Unfortunately the mechanisms that regulate neuronal apoptosis are complex. However, it is this very complexity that provides us with a wide array of potential targets for the development of anti-apoptotic strategies. Thus, our lab is currently exploring the molecular and cellular mechanisms responsible for neuronal apoptosis, with a particular focus on the role of the metals copper, zinc, and iron. Each of these metals is essential for normal central nervous system (CNS) development and function. However, imbalances, either excess or deficiency, can result in neuronal apoptosis. In this review, we show the relationship between these metals in neurodegenerative disorders and CNS injury, and the mechanisms that govern neuronal survival and apoptosis.
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PMID:Trace metal regulation of neuronal apoptosis: from genes to behavior. 1612 8

7beta-Hydroxycholesterol has been previously demonstrated to inhibit astrocytosis in injured cortex or spinal cord of rats. In this study, we explored the inhibitory effects of the liposome containing 7beta-hydroxycholesterol on the reactive astrocytosis caused by the injection of iron into the hippocampus of rats and furthermore evaluated the involvement of reactive astrocytosis in iron-induced epilepsy. Injection of ferric chloride solution unilaterally into the hippocampus of rats induced spontaneous spiking activity ipsilaterally then developed into bilateral hippocampi and generalized convulsive seizures within the first week post-operation, and spontaneous epileptiform activity and generalized seizures lasted as long as 2 weeks post-operation, whereas none of the rats injected with sodium chloride solution unilaterally into the hippocampus developed generalized seizures. With immunohistochemistry and Western blot analyses, apparent reactive astrocytosis in bilateral hippocampi was detected using antibody against glial fibrillary acidic protein 14 days after the injection of ferric chloride solution, but no significant differences were found in the amount of synaptophysin protein, a presynaptic vesicle protein, as compared with the rats injected with sodium chloride solution. Infusion of liposome suspension containing 7beta-hydroxycholesterol into the same site immediately after the injection of ferric chloride solution reduced the extent of the reactive astrocytosis by 50%-55% of the amount of glial fibrillary acidic protein in the hippocampi of both hemispheres, and non-significantly elevated the amount of synaptophysin protein in both sides of hippocampus. However, these effects did not significantly modify the seizure latency and the incidence of generalized seizures in the rats. These findings demonstrate the effects of 7beta-hydroxycholesterol on the inhibition of reactive astrocytosis caused by iron deposition in the hippocampus of rats, and suggest that the reactive astrocytosis may not play a causal role in the development of iron-induced seizures.
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PMID:7beta-hydroxycholesterol reduces the extent of reactive gliosis caused by iron deposition in the hippocampus but does not attenuate the iron-induced seizures in rats. 1644 40

Forty five (24 male & 21 female) moderate to severe degree of predialysis CRF patients were prospectively studied over a period of 6 months (July- December, 2004) to see the effect of Recombinant Human Erythropoietin (rHuEpo/EPO) therapy on renal anaemia, progression of renal excretory function & quality of life at 3 and 6 months intervals from the starting of EPO therapy. Mean +/- SD age of the patients was 56 +/- 12 (30-77 yrs) and causes of CRF were Diabetic Nephropathy (DN)=15 (33%), Chronic Glomerulonephritis (CGN) =14(31%), Hypertension (HTN)=11(21%), Chronic Pyelonephritis (CPN)=03 (6.5%) and Obstructive Uropathy (OU)=02 (4.5%). Doses of rHuEpo was 80-100 IU/k week subcutaneously (SC) until the target Hb 11gm% & Hct 30% were achieved; there after the dose was titrated as appropriate. Serum Iron & Ferritin levels were also kept within normal reference level by iron therapy during the study period. Mean +/- SD base line (before starting EPO therapy) level of haemoblobin were 8.4 +/- 0.81(gm%), Hct 27.86 +/- 1.6 (%), blood urea 21.72 +/- 10.5 (mmol/L), S. creatinine 431.93 +/- 228.79 (mmol/L) & Ccr. 21.25 +/- 10 mum respectively. The results showed that significant improvement of haemoglobin level occurred (gm%) from 8.4 +/- 0.81 (gm%) to 9.51 +/- 1.02 (p<0.001) at 3 months and 8.4 +/- 0.81 to 11.10 +/- 1.4, (p<0.001) at 6 months interval. Haematocrit (Hct%) value also significantly increased from 27.86 +/- 1.5 to 30.57 +/- 3.62, (p<0.001) at 3 months and 27.86 +/- 1.5 to 32.81 +/- 3.92 (p<0.001) at 6 months of EPO therapy. Mean blood urea and S. creatinine levels decreased from base line level during the study period but did not show any statistical significance. There was no significant side-effects like uncontrolled hypertension, seizure or hyperviscosity syndrome in any of the study population. The quality of life in terms of improvement of physical ability and sense of well being were also improved in all the study patients. In conclusion, this study showed that the effect of rHuEpo therapy is beneficial for the correction of renal anaemia, can delay the progression of renal failure and improvement of overall quality of life in predialysis CRF patients.
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PMID:Effect rHuEpo on predialysis CRF patients: study of 45 cases. 1696 14

Mutations in the gene for the astrocyte specific intermediate filament, glial fibrillary acidic protein (GFAP), cause the rare leukodystrophy Alexander disease (AxD). To study the pathology of this primary astrocyte defect, we have generated knock-in mice with missense mutations homologous to those found in humans. In this report, we show that mice with GFAP-R76H and -R236H mutations develop Rosenthal fibers, the hallmark protein aggregates observed in astrocytes in AxD, in the hippocampus, corpus callosum, olfactory bulbs, subpial, and periventricular regions. Astrocytes in these areas appear reactive and total GFAP expression is elevated. Although general white matter architecture and myelination appear normal, when crossed with an antioxidant response element reporter line, the mutant mice show a distinct pattern of reporter-gene induction that is especially prominent in the corpus callosum, and histochemical staining reveals accumulation of iron in the same region. The mutant mice have a normal lifespan and show no overt behavioral defects, but are more susceptible to kainate-induced seizures. Although these mice demonstrate increased GFAP expression by themselves, further elevation of GFAP via crosses to GFAP transgenic animals leads to a shift in GFAP solubility, an increased stress response, and ultimately death. The mice do not display the full spectrum of pathology observed in human infantile AxD, but may more closely resemble the adult form of the disease. These studies provide formal proof linking GFAP mutations with Rosenthal fibers and oxidative stress, and correlate gliosis and GFAP protein levels to the severity of the disease.
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PMID:Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. 1706 56


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