Multiple projection of the visual field to the medical portion of the dorsal lateral geniculate nucleus and the adjacent nuclei of the thalamus of the cat.
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The pharmacokinetic behaviour of alcuronium is described for nineteen patients undergoing anaesthesia for elective surgery. Eleven patients received a single bolus intravenous dose of 0.25 mg/kg, while 8 patients required additional doses of 0.125 mg/kg. A two-compartment open model was found to describe adequately both the single dose and multiple dose data for the majority of patients. No significant differences were found in the model-independent pharmacokinetic parameters between the single and multiple dose studies. Mean values for the pooled data for the half-life (t 1/2 beta), apparent volume of distribution (Vd beta), volume of distribution at steady-state (Vdss), volume of the central compartment (Vc) and plasma clearance (Clp) were 198.75 min, 24.261, 20.891, 8.181 and 90.22 ml/min respectively. Evoked muscle twitch response was monitored in 17 of the patients to assess the degree of relaxant blockade. The bolus dose of alcuronium produced complete block in 9 patients and between 95 and 99% block in the remainder. The time of onset to maximum block ranged from 3 to 30 min with the concurrently measured plasma levels of alcuronium being 0.79 to 2.25 microgram/ml. The time taken following bolus administration to 5% recovery (95% paralysis) was a mean of 42 min and the corresponding mean alcuronium plasma concentration was 0.78 microgram/ml.
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The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%.
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IgE antibodies that bind the muscle relaxant alcuronium were found in sera from six patients who experienced anaphylactic-like reactions following administration of the drug during induction of anaesthesia. Drug-specific antibodies were detected by radioimmunoassay employing a covalently coupled alcuronium-Sepharose complex and 125I-labelled anti-human IgE. Quantitative inhibition studies undertaken with the sera revealed specificity differences between IgE antibodies from different patients. One serum reacted with alcuronium but not with five other muscle relaxants, decamethonium, gallamine, pancuronium, succinylcholine and tubocurarine. IgE antibodies in the other sera cross-reacted with the muscle relaxants, other quaternary ammonium compounds and some pharmacologically unrelated drugs including promethazine, morphine, neostigmine and pentolineum. The inhibition experiments revealed that the alcuronium-IgE reaction could be prevented or diminished by structures containing a substituted ammonium ion. As these ions occur widely in man's environment in drugs, cosmetics, disinfectants, foods and industrial materials, it seems possible that sensitization of patients may occur without previous exposure to muscle relaxants.
The effect of chronic ethanol intake on neuromuscular function has been analyzed by using a rat tibial muscle preparation. The time-course of single twitches, trains-of-four, tetanus and post-tetanic facilitation with and without blockade with alcuronium was evaluated. A decrease in these parameters was observed, being more pronounced in ethanol fed rats during 10 than 30 days. The twitch was the most affected parameter. After recovery of alcuronium blockade, the depressant effects of ethanol were completely reversed. These data suggest that low but sustained ethanol blood levels causes evident alterations of neuromuscular function due, probably, to a postjunctional action.
Bisnordihydrotoxiferine has been isolated as the major alkaloid from the root bark of Strychnos trinervis. This compound shows a wide antimicrobial spectrum against gram-positive, gram-negative and acid-fast microorganisms, filamentous and yeast-like fungi and also phytopathogenic microorganisms. Preliminary studies also reveal some cytotoxic activity in KB cells which was confirmed by tests against sarcoma 180 tumors.
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