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)

Intermittent O2 breathing is a proven means of delaying pulmonary O2 toxicity during exposure to hyperbaric oxygen. The effect of an intermittent exposure in the pressure range toxic to the CNS was studied. Conscious, unrestrained rats, implanted with cortical EEG electrodes were subjected at 5 and 6 ATA to alternating periods of 7 min O2 and 7 or 10 min of either air, normoxic nitrox, or N2O-air (the latter mixture being equinarcotic to pure O2). Altogether, nearly half of the animals survived 90 min of intermittent breathing, with no grossly abnormal EEG patterns. At that time, labored breathing (associated with mild lung pathology) supervened. In the remaining animals, seizure patterns in the EEG appeared after a mean cumulative O2 breathing time of 20 min (compared to 9 min during a continuous exposure). Forty percent were affected while breathing the alternating mixture (low-PO2 seizures), mostly soon after switching of the gas. The nature of the alternating mixture did not affect the outcome of the high-PO2 seizures nor did the length of the interim periods. Normoxic nitrox increased and N2O-air reduced the incidence of low-PO2 seizures. At 5 ATA only 10% of the animals experienced high-PO2 seizures. While swift reversibility of the toxic process is indicated, the low-PO2 seizures with as yet an undetermined mechanism pose a serious obstacle for intermittent exposures at this pressure range.
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PMID:Central nervous system oxygen toxicity in the resting rat: postponement by intermittent oxygen exposure. 320 31

Large intramuscular doses of a water-miscible preparation of vitamin A (500,000 I.U. retinyl acetate/ml), vitamin E (50 I.U./ml) and vitamin D2 (50,000 I.U./ml) were administered to young monkeys (Macacus fascicularis) weighing 1-1.8 kg. At vitamin A doses equivalent to 200 mg retinol/kg or higher, early signs of acute toxicity included yawning, apparent drowsiness, nausea and vomiting, head shaking, neck hyperextension, motor hyperactivity and coordination. These immediate signs were first noted 3-35 minutes after injection. Following apparent recovery at 1-2 hrs, longer term signs of toxicity, such as decreased activity, malaise, drowsiness, loss of appetite, loss of weight, and itchiness of the skin, appeared within 1-6 days, depending on the dose. Monkeys receiving the highest lethal doses became progressively weaker, showed labored breathing, lapsed into a coma, lost simple reflexes and then died. Respiratory failure usually preceded the cessation of heart beat. In some monkeys on a lower but lethal dose, death was preceded by generalized convulsive seizures. The time of onset of the first sign and survival time were inversely proportional to the dosage, but in individual monkeys no correlation existed between onset time and survival time. Female monkeys seemed to succumb faster to a lethal dose than male monkeys. All animals receiving the equivalent of 300 mg retinol/kg died. Under the conditions used, the LD50 was estimated to be 168 mg retinol (560 000 I>U.) per body weight.
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PMID:A lethal hypervitaminosis A syndrome in young monkeys (Macacus fascicularis) following a single intramuscular dose of a water-miscible preparation containing vitamins A, D2 and E. 697 50

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, decreased muscle tone, ataxia, prostration, and labored breathing. Death was observed after intraperitoneal but not oral administration. A consistent drug-related effect noted in all multiple-dose studies with this compound was decreased body weight and food consumption. The only other consistent change noted in multiple-dose studies with felbamate was an increase in liver weight (relative and absolute) in the rat and dog which was accompanied in some cases by increases in serum enzyme levels. No histopathological changes were observed in the liver that could explain these elevated serum enzyme levels. Based on the results of these studies it was concluded that long-term administration of felbamate in human clinical trials was warranted.
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PMID:Acute, subchronic, and chronic toxicity studies with felbamate, 2-phenyl-1,3-propanediol dicarbamate. 984 29

The goal of this study was to identify objective criteria that would reliably predict imminent death in aged mice. Male and female ICR mice (age, 8 mo) were subcutaneously implanted with an identification chip for remote measurement of body temperature. Mice then were weighed and monitored regularly until spontaneous death occurred or until euthanasia was administered for humane reasons. Clinical signs that signaled implementation of euthanasia included inability to walk, lack of response to manipulation, large or ulcerated tumors, seizures, and palpable hypothermia. In mice that died spontaneously, gradual weight loss was the most frequent and earliest sign of imminent death. Hypothermia developed during the 2 wk prior to death. Slow or labored breathing were observed in about half of the mice before death. A composite score of temperature x weight can be used to provide an objective benchmark to signal increased observation or euthanasia of individual mice. Such assessment may allow the collection of terminal tissue samples without markedly altering longevity data, although application of this criterion may not be appropriate for all studies of longevity. Timely euthanasia of mice based on validated markers of imminent death can allow implementation of endpoints that alleviate terminal distress in aged mice, may not significantly affect longevity data, and can permit timely collection of biologic samples.
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PMID:Identification of markers for imminent death in mice used in longevity and aging research. 2058 57