Sodium thiosulphate was introduced into therapy several years ago by one of us, in cooperation with Dennie and McBride, as a means of relieving certain types of intoxication, such as the metallic toxemias. The drug, simple as it may seem, has fully met the vital test of yielding prompt relief when administered soon after the development of the toxic symptoms. Our interest has led us now for several years to a further study of its modus operandi. The authors have previously reported on the excretion of arsenic in cases of arsenic dermatitis. The action of sodium thiosulphate is least marked in cases of inorganic arsenic poisoning; next in order, it is effective after the pentavalent organic preparations; and the greatest efficiency is reached with the trivalent group represented by the arsphenamines. The activity of sodium thiosulphate cannot be judged by the excretion of arsenites. It has been pointed out by Mueller and Myers that the skin and the liver are the two main organs involved in intoxication, and on this basis sodium thiosulphate serves as a protective drug in respect to the autonomic nervous system. The present report offers clinical and experimental evidence in favor of the efficacy of freshly prepared sodium thiosulphate in hastening the excretion of arsenic either in its inorganic or in its organic form. Furthermore, sodium thiosulphate does not disturb the therapeutic action of the arsphenamine compound in its action on Trypanosome equiperdum. Prompt results have been noted by leading syphilologists in connection with dermatitis and jaundice following the use of the arsphenamine group. Some clinical data have recently been made available through the investigations of H. H. Dale, of the British Medical Research Committee.
The study of the relation between the antiseptic action and the chemical constitution of synthetic dyes dates back to the period of Paul Ehrlich who began with one group of dyes known as azo dyes, including trypan red, trypan blue and trypan violet. The other group of dyes consisted of basic tryphenyl-methane dyes, including parafuchsin, methyl violet, pyronin G and other similar substances, known as neurotrophic dyes because of their ability to stain nerve tissue. McIntosh and Fildes reported that arsenic could not be found in the brain tissue, due to a lack of affinity between the brain substances and the inability on the part of the drugs to penetrate into the brain. In vitro experiments show that this is purely a question of physical penetration. The same authors classified the dyes as, (1) those which stain the central nervous system, and (2) those which do not stain the central nervous system. They conclude that these variations were dependent upon the question of solubility. The subject further resolved itself into the fact that neurotropic substances are lipotropic, and before a substance can penetrate into a cell it must be solu'ble in the cell membrane or possess a distinct osmosis. Smith and Waddell increased the permeability of the choroid plexus to arsphenamine with methyl violet. Their conclusion is that methyl violet when given intravenously does not increase the permeability. Cornwall and Myers showed that arsenic actually penetrated the cord and the brain. These experiments are being repeated with the idea of checking up the effect of transfusion just previous to the sacrificing of the animal. Fordyce and Myers studied the action of salvarsan, neosalvarsan, silver salvarsan and tryparsamide on penetration of arsenic into the central nervous system in general paresis and cerebrospinal syphilis.
The reaction of the involuntary nervous system to intravenous injection of salvarsan, neosalvarsan and silver salvarsan, and the influence of this reaction on the neutrophile leucocytes have been discussed in two previous articles. It was found that in humans the number of white blood cells decreases for a short period immediately following an intravenous injection of salvarsan. This sudden decrease is prolonged in patients who present manifestations of the so-called nitritoid crisis. An intravenous injection of silver salvarsan, however, is not followed by a similar reaction. These findings, which were discussed at length in the foregoing articles, led to a study of the details of this leucocytic reaction, the main problem being: Where are the leucocytes during the period of their absence from the periphery? It seemed probable that they had migrated to the inner organs. But no proof of this theory could be elicited from the human body, as it is impossible to examine intimately the inner organs of human beings after salvarsan injections except in rare instances, and never in a sufficiently large number of instances to warrant definite conclusions. Furthermore, it is known that abdominal operations, as well as general narcosis, are in themselves productive of a similar decrease in the number of leucocytes in the peripheral vessels. The only avenue of approach to a solution of this problem, therefore, was a study of the conditions resulting in the animal body. Animal experiments along these lines necessitated preliminary comparative tests. In different series of animal tests a similar decrease in the number of leucocytes was observed after the intravenous injection of salvarsan. The decrease is less pronounced or is entirely absent when silver salvarsan is administered.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSignificance and Danger of Spray ResidueC. N. Myers, Binford Throne, Florence Gustafson, and And Jerome KingsburyCite this: Ind. Eng. Chem. 1933, 25, 6, 624–628Publication Date (Print):June 1, 1933Publication History Published online1 May 2002Published inissue 1 June 1933https://doi.org/10.1021/ie50282a011RIGHTS & PERMISSIONSArticle Views46Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (770 KB) Get e-Alerts
Gold preparations have recently found clinical application in tuberculosis and certain diseases of the skin. Among these preparations are Sanocrysin or gold and sodium thiosulfate, Krysolgan and Triphal. Sanocrysin or gold and sodium thiosulfate was originally prepared by Fordos and Géllis in 1845. It has been improved on by Mollgaard and contains about 37.5 per cent gold and 26.2 per cent sulphur, which would correspond to the formula 3Na2S2O3Au2S2O3 4H2O. Triphal, one of the other preparations studied by us from a toxicological point of view, contains approximately 44 per cent gold and 7.1 per cent sulphur, nd this corresponds to the chemical formula C6H3N-NH-CSAu-COONa 2H2O or the sodium salt of Aurothiobenzimidazolcarboxylic acid. Previous investigations have shown that under some conditions, gold salts tend to produce marked kidney and liver damage as well as urticaria, pruritus and erythematous eruptions. With these possibilities in mind, the present report deals with a toxicological study of the three common gold preparations which are available. Examination of Tables I, II and III, shows the effects of the injection of these drugs in normal Albino rats, with the action upon the lungs, liver and kidneys. The injections were carried out on normal healthy Albino rats from a common source; they were maintained on a constant, well balanced diet composed of whole wheat flour, corn meal, skim milk, calcium carbonate, and sodium chloride, together with the addition of 2 per cent of active coct liver oil. Examination of these tables further shows definitely the marked difference in toxicity of these various preparations, and this observation alone has a distinct bearing on the clinical application of these drugs.
The existence of at least three vitamines, namely the antiscorbutic, the so called fat-soluble, and the antineuritic, is known at the present time.This paper deals principally with the antineuritic vitamine.The important stage in the chemical investigation of this substance began with the classical research of Eijkman in 1897, who was able to show that rice polishings contain the antineuritic vitamine and that this substance is dialyzable and not precipitated from its solution by alcohol.Eijkman's work stimulated Funk to attempt the chemical isolation of the substance.In a series of researches he established the following facts.First of all he found that the curative substance is of a simple nature, as yeast can be hydrolyzed for 24 hours with 25 per cent sulfuric acid without causing the destruction of its vitamine.The active substance is precipitated by phosphotungstic acid and is mainly found in the silver nitrate-baryta fraction, when subjected to silver precipitation.This fraction contains three classes of biological products; namely, the histidine, pyrimidine, and nicotinic acid groups.On working up these fractions from yeast Funk isolated three substances which on analysis yielded the following formulas: C24H1909N5, C23H2309N5, and C6H502N (nicotinic acid).By using the same or similar methods, Suzuki, Shimamura, and Odake, Vedder and Williams, and E&e, Evans, Moore, Simpson, and Webster were also able to isolate more or less active vitamine fractions from active raw material.Similar fractions were obtained by Funk from milk, brain, lime juice, rice polishings, and cod liver oil.
