IMINAZOLYLETHYLAMINE is the amine which is produced when carbon dioxide is split off from histidine. It was first prepared synthetically by Windaus and Vogt'. Recently Ackermann2 obtained a large yield of the base by submitting histidine to the action of putrefactive organisms. It has been shown that several of the amines thus related to amino-acids possess marked physiological activity. The activity of j8-iminazolylethylamine was discovered in the course of the investigation of ergot and its extracts by G. Barger and one of us3, who attributed this structure to a base which they obtained, and which in minute doses produced tonic contraction of the uterus. The synthetic substance, and the base produced by splitting off carbon dioxide from histidine by bacterial action or by chemical means, were found to have an identical action. Meanwhile Kutscher4 had simultaneously and independently described the isolation from ergot of a base having this action and presumably identical with that obtained by Barger and Dale. By its chemical properties this first ergot base of Kutscher was not distinguishable from 8-iminazolylethylamine; but certain apparent differences in the physiological action of the two bases, observed by Ackermann and Kutscber-5, led them to the conclusion that the ergot base, though closely related to 8-iminazolylethylamine, is not identical with it. The alleged difference in action, on the existence and cause of which our experiments throw light, was as follows: the 1 Ber. d. deutsch. chem. Gesell. xi,. p. 3691. 1907.
The method devised by Boeck and Drbohlav for the cultivation of E. histolytica has been successfully used for cultivating this species and various other entozoic amoebae of man and monkeys.Various modifications of the original technique have been tried, and several improvements are here described. Among these are methods of cultivation (involving the addition of solid rice-starch to the medium) whereby (1) more luxuriant and prolonged growth of the amoebae, and (2) all stages—including encystation and excystation—in the life-cycle of E. histolytica and other species can be obtained in vitro.Methods by which cultures of entozoic amoebae can be initiated from encysted forms have been discovered and are also described, and some indications are given for the isolation of pure strains from mixed cultures.The influence of the accompanying bacterial flora upon the various amoebae cultivated has been studied, and is briefly discussed in the light of certain experimental findings.Loss of infectivity to kittens has been observed in E. histolytica as an apparent result of cultivation in media containing solid starch.
IN our earlier papers (1, 2, 3) on the action of histamine we have been chiefly concerned with the physiological analysis of the evanescent effects of smaller doses, though mention was made in our first paper of the phenomena of fatal histamine-poisoning in rabbits and guinea-pigs and of the prolonged collapse and coma caused by injecting large doses into the unansesthetised cat. The essential difference between its actions in rodents and carnivXora is well illustrated by the modifications introduced by anaesthesia. The normal rabbit or guinea-pig is easily killed by a relatively small intravenous injection of histamine, but suffers little harm from a much larger injection when deeply under the influence of an anaesthetic. We have shown that the cause of death in the guinea-pig is bronchial constriction, in the rabbit obstruction of the pulmonary circulation leading to acute dilatation of the right ventricle, and have pointed out that the reaction of plain muscle to histamine, on which the effects depend, is weakened by an anaesthetic. The unanaesthetised cat, on the other hand, recovers from the depressant effects even of very large doses, while in the same species under an anaesthetic even moderate injections of histamine often produce a fatal circulatory collapse and respiratory failure, from which the animal does not recover even after prolonged application of artificial respiration. E. Mellanby(4) has studied the onset of this condition in ansesthetised cats as the result of absorption of histamine from the small intestine. Our object in this paper is to examine the nature and the mode of production of this "histamine-shock" in ansesthetised cats. The fact that the condition has many features in common with a number of pathological conditions, loosely classified as "shock," gives to its analysis a more than immediate interest.Methods. Most of our experiments have been made on cats, a few only on dogs. It will be clear from what has been said above that the
It is now recognized, by all competent observers, that emetine is a specific therapeutic agent for the treatment of amoebic dysentery; but although it is known that a thorough course of emetine, in some form, will eradicate an infection with Entamoeba histolytica from most human beings, there is still complete ignorance as to how the cure is effected. The obvious hypothesis, that emetine is a specific poison for E. histolytica, has not hitherto been supported by adequate experimental evidence. It is true that observers have described experiments in which the alkaloid, in high dilution, has apparently killed various amoebae in vitro; but these experiments either ignored the peculiarly specific action of emetine in vivo on E. histolytica, or were carried out without adequate controls.
IN a previous communication' we described the general features of the action of 8-Iminazolylethylamine. We have now to describe and discuss certain additional and supplementary observations.
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