T-2 toxin as an emetic factor in moldy corn.
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Extracts of Fusarium poae (NRRL 3287) grown either on sterile corn at 8 C or in Richards solution at room temperature were shown to have emetic activity in pigeons at nonlethal concentration under conditions of oral and intravenous administration. The causative agent was found to be T-2 toxin (3-hydroxy-4,15-diacetoxy-8-[3-methylbutyryloxy]-12,13-epoxy-Delta(9)-trichothece ne). Oral and intravenous mean toxic dose values for this compound were found to be 0.72 and 0.15 mg/kg, respectively, as compared with an oral mean lethal dose of 2.75 mg/kg. The fact that T-2 toxin causes emesis at nonlethal concentrations may explain, at least in part, the observance of vomiting as a symptom resulting from ingestion of cereal grains infected with toxic Fusarium species containing T-2 or a similar toxin. (+info)
Identification of a fourth staphylococcal enterotoxin, enterotoxin D.
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A fourth staphylococcal enterotoxin was identified serologically with antiserum to the very crude enterotoxic products of growth of a strain which also produces enterotoxin C, and then with antiserum to the considerably purified enterotoxic antigen of a strain which produces only the new enterotoxin. The identification of this antigen as enterotoxin D was based on the following observations. It was produced by strains which do not produce enterotoxins A, B, or C; it was absent in the growth products of nonenterotoxigenic strains; when appreciably purified, it was associated with emetic activity in the cat, and its biological activity was neutralized only by antisera containing its specific antibody and not by antibodies to enterotoxins A, B, and C. Staphylococcal strain 494 (ATCC 23235) was selected as the prototype strain. The production of this enterotoxin alone and together with enterotoxin A by strains of food-poisoning origin indicates that its role in food poisoning is second in frequency only to that of enterotoxin A. The incidence of production of enterotoxins A, B, C, and D, and of unidentified cat emetic substances by strains from several source categories, is presented. (+info)
Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin).
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1. A titration assay with two end points is described for comparison of the emetic and lethal potencies of digitalis-like drugs.2. A drug was infused at constant rate to a conscious, unrestrained cat, through an indwelling venous cannula. At the moment of vomiting the cat was rapidly anaesthetized and infusion continued at the same rate until the moment of cardiac arrest.3. With very slow and very fast infusions, the emetic and lethal doses tended to rise. In the range between these extremes (which varied from drug to drug) they were independent of time.4. The observations could be accounted for by analogue computation, assuming that the drugs entered an initial pool and were distributed at finite rates to receptors in the CNS (vomiting centre) and heart.5. Half times of metabolic loss derived from this computation for digitoxin, digoxin and ouabain (17, 9.9 and 1.8 h, respectively) were in the same ratio as the threefold longer half times reported for these drugs in man.6. When measured with infusion rates in the time independent range, the ratio of lethal to emetic doses did not vary between the drugs studied. All caused vomiting at 40% of the lethal dose.7. From a review of the literature, the emetic and cardiotoxic actions of digitalis-like drugs appear inseparable and probably share a common biochemical mechanism.8. It is concluded that foreseeable improvements in digitalis-like drugs are small and would depend on the elimination of any local emetic effect on gut receptors which they may have. (+info)
Enkephalin receptors in the emetic chemoreceptor trigger zone of the dog.
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1 The emetic action of Met-enkephalin, morphine and naloxone was studied following their administration into the cerebral ventricles of dogs through chronically implanted cannulae and the effect on the responses of ablating the chemorceptor trigger zone (CTZ) was investigated. The opiate antagonist, naloxone, was used to determine the role of enkephalin receptors in emetic responses.2 Administration of Met-enkephalin (1.0 mug/kg) into the IVth ventricle regularly evoked emesis with an average latency of 35 s. A dose of morphine (2.5 mug/kg) which was five times larger was required for a consistent emetic response when introduced into the lateral cerebral ventricle (i.c.v.) as compared to the dose required by the IVth ventricular route. The latency of emetic responses by the latter route of injection of morphine was shorter. This is in accord with an action of morphine on the emetic CTZ.3 After bilateral ablation of the CTZ, intraventricular injections of Met-enkephalin and morphine failed to produce emesis even when given in doses that were 5 to 10 times the dose which regularly elicited emesis in animals with intact CTZ. The emesis produced in dogs by intraventricular Met-enkephalin and morphine is thus fully accounted for by an action on the CTZ.4 Naloxone (i.c.v.) in doses up to 10.0 mug/kg did not cause emesis. However, higher doses of naloxone elicited dose-dependent emesis in dogs. The 100% emetic dose of naloxone was found to be 160 mug/kg and the latency of emesis was 180 s. Unlike Met-enkephalin and morphine, naloxone continued to elicit emesis in CTZ-ablated animals.5 Pretreatment with intraventricular naloxone (1 to 8 mug/kg) blocked the emetic responses induced by intraventricular Met-enkephalin and morphine but not that to apomorphine. The selective protective action of the opiate antagonist against Met-enkephalin and morphine supports the presence of enkephalin receptors in the emetic CTZ. (+info)
Determining the effective emetic dosage of tetrapotassium pyrophosphate (TKPP) in dogs.
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The effect of TKPP on emesis was examined in adult "conditioned random source" mongrel dogs. Only dogs that exhibited emesis with CuSO4, were used. The effect of dosage and concentration of TKPP on emesis was highly significant. The effective combinations of dose and concentration were 4,800, 2,400, or 1,200 mg/head at 5, 10, or 20%. In all the tested dogs, 4,800 mg of 20% TKPP was effective inducing emesis. The mean latency of emesis in dogs was 7 min, 33 sec (95% confidence limits: 5 min, 58 sec 9 min, 7 sec). (+info)
Site of emetic action of oral copper sulfate in dogs. (I) Thresholds of various portions of gastrointestinal tract to locally applied copper sulfate.
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Emetic thresholds to copper sulfate administered into the Pavlov pouch, Forrest pouch, Thiry fistulas of the jejunum and ileum, and duodenal, jejunal and ileal catheters were measured in dogs to conjecture the site of emetic action of copper sulfate. The oral emetic threshold had been measured preoperatively. In the stomach, the pyloric antrum had a high sensitivity, while the corpus had a low sensitivity to the topically applied copper sulfate. In the intestine, the sensitivity was high in the duodenum, whereas a low sensitivity was noted in the jejunum. Almost no sensitivity was observed in the ileum. Thus it would appear that the site of the emetic action of copper sulfate was the pyloric antrum and/or duodenum. (+info)
Site of emetic action of oral copper sulfate in dogs. (II) Importance of lower duodenum.
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Sensitivities of the stomach and duodenum to oral copper sulfate emesis were compared in dogs. 1) Dogs equipped with a stainless stell cannula in the middle of the duodenum were challenged to the oral threshold emetic dose of copper sulfate administered by a gastric tube. When the cannulas were opened, the oral thresholds were not effective to elicit vomiting in the most cases (1/13). Fairly rapid and high rate recoveries of copper through the open cannula were noted. With the closed cannulas, the thresholds were highly effective (16/16). 2)In the dogs with a cannula at the upper part of the jejunum, the oral threshold doses were always effective whether the canula was opened (9/9) or closed (11/11). Recovery rates of copper from the cannula were usually poor. 3) The oral thresholds administered into the proximal end or the middle of the duodenum through a PVC tubing were equally effective. 4) Although copper sulfate might irritate the stomach and upper duodenum to evoke vomiting, these results suggested a higher sensitivity of the lower duodenum. (+info)
Emetic reflex arc revealed by expression of the immediate-early gene c-fos in the cat.
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The organization of the central neuronal circuitry that produces vomiting was explored by mapping the distribution of c-fos protein (Fos)-like immunoreactivity (FLI) as a monitor of functional activity. The brainstem and spinal cord were examined in cats administered multiple emetic drugs (cisplatin, lobeline, protoveratrine, naloxone, apomorphine) or control saline injections. Some animals were decerebrated, paralyzed, and artificially ventilated to avoid possible Fos expression induced by sensory feedback or fluid depletion during vomiting. Fictive vomiting was identified in these animals by a characteristic pattern of respiratory muscle nerve (phrenic and abdominal) coactivation. Tissues were immunoprocessed using an antibody raised against amino acids 1-131 of Fos and the avidin-biotin peroxidase complex method. Enhanced nuclear FLI was observed in experimental animals along portions of the sensorimotor emetic reflex arc, including the nodose ganglia, area postrema, nuclei of the solitary tract (especially medial and subpostrema subnuclei), intermediate reticular zone of the lateral tegmental field, nucleus retroambiguus, C2 inspiratory propriospinal cell region, and dorsal vagal and phrenic motor nuclei. Enhanced FLI was also detected in the raphe magnus, subretrofacial nucleus, and spinal dorsal horn. Regions showing no recognizable differences in FLI between experimental and control animals included the vestibular, cochlear, spinal trigeminal, subtrigeminal, and lateral reticular nuclei. Only minor differences were observed in the distributions of FLI between intact and decerebrate animals. No unique, well-defined group of labeled neurons that might function as a "vomiting center" could be identified. Instead, the pattern of c-fos expression suggests that neurons involved in coordinating the emetic response may radiate from the area postrema and nucleus of the solitary tract to an arc in the lateral tegmental field implicated in somato-autonomic integration. (+info)