THE object of this paper is to show that the antiscorbutic activity of our " hexuronic acid" preparations is due to the acid itself and not to a contamination by some more potent substance. The authors think that they have demonstrated this and that the experiments presented give definite evidence for the identity of the acid and vitamin C. In accordance with the latest results of chemical analysis [Karrer et al., 1933; Cox et al., 1932] "hexuronic acid" will henceforth be called ascorbic acid [Szent-Gyorgyi and Haworth, 1933]. PREPARATION OF ASCORBIC ACID FROM PAPRIEA. Progress in our work was dependent on the possibility of obtaining larger quantities of ascorbic acid. Unfortunately, adrenal glands, the only material heretofore suitable for large scale preparation, were not available in the necessary quantity. All our efforts to prepare ascorbic acid on the large scale from tomatoes, cabbages or oranges failed. In a quest for more suitable material, we have found that local varieties of paprika (Hungarian red pepper, Capsicum annuum) showed a strikingly high reducing power. 1 cc. of the juice of the fresh and ripe fruit reduces in acid solution on the average 2-4 cc. of 0.01 N iodine or the equivalent quantity of dibromophenolindophenol. This would correspond to about 2 mg. of ascorbic acid if this substance were solely responsible for the reduction. In animal experiments paprika juice shows a strong antiscorbutic activity. With 0-25 or 0 5 cc. of the juice, guinea-pigs were kept practically free from scurvy in a 53-day experiment (see Table II). Throughout this experiment the same juice was used, which was kept in vacuo at 00. This brings out the fact, that paprika juice not only contains relatively large amounts of the antiscorbutic factor, but also contains it in a relatively stable condition, suitable for chemical work. 50 kg. of paprika, freed from the core, were minced in a meat grinder and 1750 g. of barium acetate in the form of a hot saturated solution were added. After standing for an hour the pulp was pressed out in a fruit press, 40 litres of juice being obtained. In absence of air this juice is stable for a period of 2 to 3 weeks. In the decanted clear liquid, 5 % of normal lead acetate is dissolved and the solution made slightly alkaline to bromothymol blue with ammonia. The precipitate is sharply separated on the centrifuge, suspended in very little water and 25 % sulphuric acid added till the fluid colours thymol blue slightly red. The lead sulphate is removed by centrifuging and 10 % of barium acetate is dissolved in the liquid. The inactive precipitate is removed on the centrifuge.
A detailed study of physiologic, biochemical, immunologic and pathologic changes resulting from acute and repeated acute injuries due to inhalation of ozone is reported. This study defines the primary chemical reaction of ozone with constituents of the body, the response of the body to the presence of the toxic substance, the physiologic functional alterations produced by acute and repeated acute injuries due to inhalation of this gas and the pathology produced by these injuries in rabbits, mice and rats. The data presented show that ozone reacts with the proteins of lung tissue to produce a severe cellular irritation which alters cell wall permeability and leads to severe pulmonary edema. Repeated acute injuries are shown to cause the development of fibrosis of the bronchioles and alveolar ducts, which limits the reserve capacity of the lung by causing the Hering-Breuer reflex to stop inspiration before complete inhalation can take place. Immunologic and biochemical changes observed which are characteristic of this type of injury are reported. It has been shown that ozone reacts in a random fashion with proteins to produce a heterogeneous antigen which will stimulate an antibody response in rabbits. The antigen created was shown to have characteristics similar to denatured protein. The severe limitation of pulmonary function by reduced tidal volume and edema and the resulting pathologic changes are reported and discussed. Submitted on July 7, 1958
WE have reported in a previous note2, that under certain conditions extracts of the adrenal medulla show an activity which cannot be explained by the adrenaline present. This activity was apparently due to a substance similar to adrenaline, but more potent than the latter. Till a chemical name can be substituted we propose to call this substance "Novadrenine."It is not the object of the present paper to give an exhaustive analysis of the physiological activity of novadrenine. We only want to give fuller evidence of the existence of such a substance, and to call the attention of research workers to this field of investigation. The present authors feel incompetent to give a definite physiological analysis, and are greatly hampered in their work by the lack of material.The existence of novadrenine is based on the observation, that under certain conditions the potency of adrenal extracts is 10-15 times higher than would correspond to their adrenaline content, estimated chemically by a colorimetric method. This high activity was only observed if the glands were excised soon after death and cooled carefully. In a great number of experiments the adrenaline content of the ox medulla was estimated colorimetrically and was found to lie between 1-2 mg. per g. of tissue, whether the extract showed a high physiological activity or not. In active extracts the physiological activity corresponded to an adrenaline content of 15-30 mg. of adrenaline per g. of medulla, a difference which could hardly be explained by an experimental error. If this latter value were correct, the gland would contain 10-15 p.c. of adrenaline by dry weight, which is impossible. It was also frequently observed that during chemical manipulations the excess activity of the extracts suddenly disappeared, the values obtained by chemical analysis and physiological estimation being then in close agreement.
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