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)

To evaluate the effects of substrate deficiency on cerebral function, metabolism, and blood flow during seizures, rats were injected intravenously with bicuculline (1.2 mg.kg-1) following a 24-hour period of starvation. During the course of seizures, blood glucose concentrations fell, and when they were reduced to below about 3 mumol.gm-1, cerebral function, metabolism, and blood flow altered. Changes in function involved the transition of an electroencephalographic pattern of bursts and suppression into one of frequent or sparse single spikes. Oxygen consumption, which initially increased at least twofold, fell toward normal or subnormal values in the single-spike period. Cortical blood flow was markedly reduced, and there was an attenuated response to carbon dioxide administration. Simultaneously, a small but clear fall was detected in the cerebral phosphorylation potential, and concentrations of glycolytic metabolites (including lactate) and citric acid cycle intermediates were reduced. Changes in amino acids and ammonia were somewhat similar to those observed in insulin-induced hypoglycemia, but since the amino acid pool did not fall, the experiments failed to give evidence that amino acids serve as oxidative substrates. The perturbation of cerebral energy state (and of levels of carbohydrate substrates and amino acids) was reversed by glucose administration; but since neither this procedure nor additional bicuculline injections could cause resumption of continuous seizure activity, the results suggest that cellular substrate depletion may have given rise to a sustained disturbance of synaptic transmission.
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PMID:Effects of bicuculline-induced seizures on cerebral metabolism and circulation of rats rendered hypoglycemic by starvation. 42 77

Clinical observations suggest that overt rhabdomyolysis may occur if severe hypophosphatemia is superimposed upon a pre-existing subclinical myopathy. To examine this possibility, a subclinical muscle cell injury was induced in 23 dogs by feeding them a phosphorus- and calorie-deficient diet until they lost 30% of their original weight. To induce acute, severe hypophosphatemia in the animals after partial starvation, 17 of the dogs were given large quantities of the same phosphorus-deficient diet in conjunction with an oral carbohydrate supplement, which together provided 140 kcal/kg per day. After phosphorus and caloric deprivation, serum phosphorus and creatine phosphokinase (CPK) activity were normal. Total muscle phosphorus content fell from 28.0+/-1.3 to 26.1+/-2.5 mmol/dg fat-free dry solids. Sodium, chloride, and water contents rose. These changes resembled those observed in patients with subclinical alcoholic myopathy. When studied after 3 days of hyperalimentation, the animals not receiving phosphorus showed weakness, tremulousness, and in some cases, seizures. Serum phosphorus fell, the average lowest value was 0.8 mg/dl (P <0.001). CPK activity rose from 66+/-357 to 695+/-1,288 IU/liter (P <0.001). Muscle phosphorus content fell further to 21.1+/-7.7 mmol/dg fat-free dry solids (P <0.001). Muscle Na and Cl contents became higher (P <0.01). Sections of gracilis muscle showed frank rhabdomyolysis.6 of the 23 phosphorus- and calorie-deprived dogs were also given 140 kal/kg per day but in addition, each received 147 mmol of elemental phosphorus. These dogs consumed their diet avidly and displayed no symptoms. They did not become hypophosphatemic, their CPK remained normal, and derangements of cellular Na, Cl, and H(2)O were rapidly corrected. The gracilis muscle appeared normal histologically in these animals. These data suggest that a subclinical myopathy may set the stage for rhabdomyolysis if acute, severe hypophosphatemia is superimposed. Neither acute hypophosphatemia nor rhabdomyolysis occur if abundant phosphorus is provided during hyperalimentation.
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PMID:Hypophosphatemia and rhabdomyolysis. 74 77

Though children with febrile convulsions only have seizures in the early stage of a febrile illness and not later, these seizures have been attributed to the fever. We studied the serum electrolyte and metabolite profiles in the later stage to see if there were fuel responses resulting in electrophysiological changes which prevented further seizure activity. On admission there was intracellular glucose starvation, as evidenced by increased ketones and lactate, and the possibility of the failure of some electrolyte pumps, as suggested by hyperuricaemia (energy crisis) and decreased serum Na+, Cl- and Ca2+. However, there was adaptive hyperglycemia and decreased serum K+. It seems likely that the hyperglycemia, induced the uptake of K+ by neurones, enabling their repolarization and hyperpolarization, which prevented further seizure activity, while Cl- influx short-circuited depolarizing currents produced by Na+ influx. Studies during recovery showed a gradual return of the metabolic and electrolyte aberrations to normality, suggesting that the provision of energy through adaptation to the stress, enabled recovery of the aforementioned pumps.
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PMID:Hyperpolarization and short-circuiting as mechanisms of seizure prevention following febrile convulsions. 277 93

The central question to be addressed in this review can be stated as "How does hypoglycemia kill neurons?" Initial research on hypoglycemic brain damage in the 1930s was aimed at demonstrating the existence of any brain damage whatsoever due to insulin. Recent results indicate that uncomplicated hypoglycemia is capable of killing neurons in the brain. However, the mechanism does not appear to be simply glucose starvation of the neuron resulting in neuronal breakdown. Rather than such an "internal catabolic death" current evidence suggests that in hypoglycemia, neurons are killed from without, i.e. from the extracellular space. Around the time the EEG becomes isoelectric, an endogenous neurotoxin is produced, and is released by the brain into tissue and cerebrospinal fluid. The distribution of necrotic neurons is unlike that in ischemia, being related to white matter and cerebrospinal fluid pathways. The toxin acts by first disrupting dendritic trees, sparing intermediate axons, indicating it to be an excitotoxin. Exact mechanisms of excitotoxic neuronal necrosis are not yet clear, but neuronal death involves hyperexcitation, and culminates in cell membrane rupture. Endogenous excitotoxins produced during hypoglycemia may explain the tendency toward seizure activity often seen clinically. The recent research results on which these findings are based are reviewed, and clinical implications are discussed.
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PMID:Progress review: hypoglycemic brain damage. 352 46

Severely ill patients often do not eat or cannot retain ingested food. Malnutrition occurs frequently in hospitalized individuals and is known to be associated with substantial changes in the pharmacokinetics of certain drugs. On the other hand, little is known about the effect of acute starvation or malnutrition on the pharmacodynamics (concentration-effect relationship) of drugs. To explore the effects of acute starvation on the pharmacodynamics of drugs that depress or stimulate the central nervous system, adult male Sprague-Dawley rats were deprived of food (but not water) for 3 days, whereas control animals had free access to food and water. Slow i.v. infusion of phenobarbital to onset of loss of righting reflex showed that the starved animals required a larger body weight normalized dose and that they had higher phenobarbital concentrations in serum, serum water, brain and cerebrospinal fluid at the pharmacologic endpoint. Refeeding of the rats for 2 or 7 days did not normalize the decreased body weight and serum total protein concentration. The starvation-associated decrease in the sensitivity of the central nervous system to the hypnotic effect of phenobarbital was only reversed slightly by refeeding for 2 days and persisted even after 7 days of refeeding. Acute starvation had no apparent effect on the dose of i.v. infused ethanol required to cause loss of righting reflex and on ethanol concentrations in serum, brain and cerebrospinal fluid at that time. The infused dose and the concentrations of pentylenetetrazol in serum, brain and cerebrospinal fluid at onset of maximal seizures did not differ significantly between starved and control (fed) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of drug action in disease states. XX. Effects of acute starvation on the pharmacodynamics of phenobarbital, ethanol and pentylenetetrazol in rats and effects of refeeding and diet composition. 361 21

PALA (N-phosphonoacetyl-L-aspartate) impairs de novo pyrimidine biosynthesis by inhibiting the enzyme aspartate transcarbamylase. During cancer chemotherapy trials the drug was given by weekly intravenous infusion. Seizures developed in 9 (11%) of the first 80 patients to receive a total dose of 9 gm/m2 or more. Seven of the affected patients had structural brain lesions; they developed seizures at a lower total dose (median of 16.4 gm/m2) than the 2 patients without clinically detectable brain lesions (115 to 130 gm/m2). Reversible encephalopathy was observed in 6 (7.5%) additional patients without clinically detectable cause other than PALA. Both seizures and encephalopathy began after the second dose of PALA or later. Experiments in rats demonstrated similar delayed-onset seizures after two or three combined systemic and intracerebral doses of PALA at 4-day intervals. Concurrent administration of uridine or carbamyl aspartate prevented the development of seizures in rats, indicating that pyrimidine starvation of the central nervous system was responsible for PALA neurotoxicity.
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PMID:Neurotoxicity of the pyrimidine synthesis inhibitor N-phosphonoacetyl-L-aspartate. 712 6

The goal of this paper is to draw conclusions about the usefulness of the standard EEG in psychiatry. In general, two thirds of psychiatric referrals for an EEG are expected to provide useful information. The emphasis in schizophrenia is placed on left-sided abnormalities, especially on the left temporal area. In mood disorders the emphasis is on right-sided foci, in addition to the controversial 6/sec spike and wave complexes, small sharp spikes and positive spikes. In the acute stage of alcoholism, a relationship is seen between the degree of intoxication and the amount of slow activity, while in the chronic stage an increase in slow activity is seen, but another change is fast activity on the temporal areas. During withdrawal a low seizure threshold can be seen as irregular bilateral spike and wave complexes. During abstinence 2-4 yr may be required before slow wave sleep is normal in all regards. Among the organic mental syndromes, delirium shows slow activity, except in delirium tremens, which often is associated with a normal record with fast activity. In dementia the prevalence of EEG abnormalities is related to the degree of impairment. After five sessions of ECT diffuse slow waves are often seen. In other conditions, among developmental disorders about one half of autistic children show abnormalities and epileptiform activity is not uncommon. Mild nonspecific abnormalities are seen in about 40% of dyslexics and also in behavior disorders. Anxiety disorders include anorexia nervosa, showing abnormal background activity related to the effect of starvation on cerebral metabolism. In panic attacks paroxysmal activity can be seen. In borderline personality positive spikes have been (again) associated with impulsivity and 6/sec spike and wave complexes with interpersonal problems. Of the drugs of abuse psilocybin and phencyclidine are often associated with generalized epileptiform patterns and with marijuana the alpha shows a decreased frequency with increased amplitude. Typically, an increase in slow activity is seen with psychotropic drugs if there is a change in the level of awareness. Finally, distinctive personality traits are, at times, seen in temporal lobe epilepsy and the phenomenon of "forced normalization" may appear when seizures stop and psychotic symptoms appear.
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PMID:A review of the usefulness of the standard EEG in psychiatry. 871

An investigation of the effects of chronic administration of ethanol by the liquid diet procedure and its subsequent withdrawal on tryptophan (Trp) metabolism and disposition was performed in rats. Treatment with the control liquid diet caused an enhancement of liver Trp pyrrolase activity and mRNA abundance. These effects are not due to the starvation associated with this feeding procedure, because they occur in rats maintained on the liquid diet ad libitum. Chronic ethanol administration in the liquid diet did not further influence the above increased expression of Trp pyrrolase mRNA but caused inhibition of pyrrolase activity in competition with the effects of the diet. The control liquid diet decreased liver Trp concentration, but exerted no significant effects on other aspects of Trp disposition. The most striking and robust finding was a highly significant elevation in both Trp pyrrolase activity and mRNA expression at 7 h following discontinuation of ethanol availability, at which time there were demonstrable behavioural signs of ethanol withdrawal. The increase in Trp pyrrolase mRNA during alcohol withdrawal may be caused by corticosterone, whose circulating concentration was also increased. The changes in Trp pyrrolase activity during ethanol withdrawal were associated with significant alterations in Trp disposition including decreased brain Trp concentration and 5-hydroxytryptamine synthesis and turnover. These alterations may play a pivotal role in the behavioural manifestations of ethanol withdrawal including the hyperexcitement underlying audiogenic seizures. We suggest that rat Trp pyrrolase gene regulation may be an important biological determinant of the ethanol withdrawal syndrome and requires further study, and that the use of the liquid diet procedure in Trp metabolic studies requires inclusion of adequate controls and special attention to the effects of the liquid diet itself.
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PMID:Effects of chronic administration and subsequent withdrawal of ethanol-containing liquid diet on rat liver tryptophan pyrrolase and tryptophan metabolism. 873 17

Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, unco-ordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene.
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PMID:The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3. 881 88

We tested the effect of moderate food or water deprivation and a combination of the two on sensitivity to hyperoxia-induced seizures in rats. Seventy rats with chronic cortical electrodes were exposed to seven experimental protocols: starvation, dehydration or a combination of both for 24 or 36 h, prior to exposure to 0.5 Mp(a)O2. Blood glucose and hematocrit were measured before and after exposure to hyperbaric oxygen (HBO). Starvation and dehydration significantly prolonged the latent period to the onset of hyperoxia-induced seizures (P < 0.05 in the Tukey test), in a dose-related manner. Our results suggest that deprivation of food or water, prior to exposure to HBO, may postpone the development of hyperoxia-induced seizures.
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PMID:Starvation and dehydration attenuate CNS oxygen toxicity in rats. 924 77


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