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260 days; Taylor2s after 14 months; Kauzmann29 after 40 days; Stevenson30 after 60 days; Tidy31 after 90 days; Pauzer, 32 in two cases, after 6 months; Witthaus, 33 in two cases, after 43 and 53 days, respectively; Autenreith after 15 months and Strzyzowski35 after 5 months.

Faust's experiments are also of great interest in this connection. He found that, after the hypodermic injection of moderate amounts of morphine into dogs, about 66 percent could be extracted from the feces. By gradually increasing the dose, this amount diminished until, after a time, no morphine was excreted in the urine or feces; and after the death of the animals, none could be extracted from the organs. He thinks that habituation to morphine is due to increased capacity of the tissues to destroy it.

From the results of Autenreith's and Strzyzowski's experiments it appears, however, that morphine undergoes decomposition, which is more extensive with aerobic than with anaerobic putrefaction. Strzyzowski estimates that under certain conditions of putrefaction, 0.5 gm. of morphine mixed with putrefying material would be detectable after 800 days. However it is possible that the effect of the dead cells on morphine is not comparable to the effects of living cells in regard to its oxidation or change into a form or forms that would not be detectable.

The absence of morphine from the liver in the case studied by myself indicates (1) that the morphine was so changed in the organism, under conditions as yet unknown, that it was impossible to detect morphine, and (2) that such a change is marked in cases of habituation to the alkaloid.

28 Taylor: On Poisons, 3d ed., p. 556.

29 Kauzmann: Dragendorff's Beiträge, p. 131.

30 Stevenson: Lancet, 1903, ii, p. 1443.

31 Tidy: Med. Times and Gazette, 1868, i, p. 497.

32 Pauzer: Zeit. f. Unt. d. Nahr. u. Genuss., 1902, v, p. 8.

33 Witthaus: Toxicology, 1911, p. 982.

34 Autenreith: Ber. d. deut. pharm. Gesell., 1901, xi, p. 494.

35 Strzyzowski: Dissert., Lausanne, 1899.

36 Faust: Arch. f. exp. Path. u. Pharm., 1900, xliv, p. 217.

STUDIES OF SOME COMPOUNDS OF CINCHOΝΑ ALKALOIDS, CERTAIN METALS AND

PHOSPHORIC ACID*

EDWIN D. WATKINS

(University of Tennessee, Memphis)

During the year 1900, under the direction of Prof. J. W. Mallet of the University of Virginia, I undertook some studies of compounds of alkaloids and metals. The alkaloids were principally those of cinchona, and the metals were of several groups. This work was abandoned before anything definite was accomplished, although I had reason to believe that some compounds had been made. In an attempt to obtain better means of treating gonorrheal urethritis than was available, I again turned my attention, in 1910, to a study of alkaloidal and metallic compounds.

Cinchona alkaloids, especially quinin, were studied because of their protoplasmic poisonous qualities, and the fact that there had been some success with quinin in the treatment of infections. The success of Helmholtz and others with quinin as an antiseptic warranted a close study of it. The known gonococcidal effect of silver commended that metal.

Many efforts to combine different acids and various radicals with quinin and silver resulted in failure until orthophosphoric acid was tried. An aqueous sol. of silver nitrate was treated with a conc. sol. of sodium phosphate to complete precipitation of the silver as phosphate. The yellow silver phosphate was washed by decantation and then on a filter. It was then treated with syrupy orthophosphoric acid to complete solution. The resulting sol. was treated with pure quinin until no more of the alkaloid was taken up. As the point of saturation was reached, the sol. changed to a darker color.

This solution was used clinically, diluted as found best by trial. There is no intention of going into a clinical discussion in this com* Proceedings of the Columbia University Biochemical Association, Feb. 5, 1915; BIOCHEM. BULL., 1915, iv, p. 227.

munication. Suffice it to say that the results from the use of the sol. in the treatment of gonorrhea have been most gratifying to those who have used it. My colleagues here and in other places have reported to me splendid success with it. Extending its use I tried it on chancroids, tonsillitis, ulcers of various kinds, and in one case of amebic infection of the colon. This last case was reported in the Journal of the American Medical Association, vol. lx, pp. 1357 and 1358 (1913). It has been found especially beneficial in chronic gonorrheal urethritis and in gonorrhea in women.

Until recently I had no positive evidence that I had made a compound of silver, quinin and the acid. All attempts to obtain crystals met with failure. Almost by accident a crystal was found in a conc. sol. which had stood unmolested in a dark cabinet from October, 1913, to December, 1914. On closer investigation two complex crystals were found in the bottom of the flask containing the conc. sol. which had stood 15 months. These were removed, carefully washed and dried. They were very dense; their color was dark yellow. One of them was used in demonstrating the presence of silver, quinin and phosphoric acid; the other is now in safe keeping for further investigation.

The crystal was decomposed in heated strong nitric acid, and the presence of silver demonstrated by precipitation with sodium chlorid and the character of the resulting precipitate. An ammonium phosphomolybdate precipitate was then obtained. On addition of strong ammonia to the nitric acid sol. of the crystal, a heavy yellow precipitate was thrown down, which was dissolved with excess of ammonia when, in the top of the sol., there appeared a flocculent white precipitate that proved to be quinin. One of my associates went over the work with me, so that there could be no mistake in it. A quantitative analysis of the crystal has not been made. That will be done at an early opportunity.

In place of silver I have made sol. of copper phosphate and zinc phosphate with quinin, quinidin, cinchonin and cinchonidin. The relative merits clinically of these sol. remains for future determination. No crystals of these compounds, if they be such, have been obtained.

ON THE ACCELERATION OF THE OXIDATION OF ALUMINIUM BY MEANS OF MERCURY

J. F. MCCLENDON

(Laboratory of Physiology, University of Minnesota)

Our knowledge of oxidations in the body is so meagre that any observations on rapid oxidations at room temperatures outside the body may be of interest. Although many accelerators (enzymes) have been extracted from living cells, such extracts, after being centrifuged, are incapable of oxidizing any of the ordinary food stuffs to carbon dioxid and water. With the aid of adsorption surfaces, carbon dioxid may be produced by some tissue extracts, but the complicated relations involved are very difficult to investigate. Unsaturated fatty acids and their compounds (such as lecithin) oxidize spontaneously in the air but no carbon dioxid is produced. Oxalic acid is completely oxidized by blood charcoal and oxygen in water; but in this case one active oxygen atom is sufficient to oxidize a whole molecule of the acid, or the molecule of formic acid, if it is split into carbon dioxid and formic acid. A less complete oxidation would hardly be expected.

A number of inorganic accelerators have been found and I wish to add one to the list. If a trace of mercury is driven into a piece of aluminium by means of an electric spark, the aluminium will burn in dry air (humidity 10 percent at 20° C.) at a rapid rate. A voluminous oxid is formed so fast that its increase may be easily detected by continuous observation for a few seconds with the naked eye or a low-power lens. The masses of white oxid grow out of the metal as plants grow out of the ground, attaining the height of a millimeter in a few minutes. In this process, the energy liberated by oxidation is partly expended in lifting the weight of the oxid against gravity, in the same way that part of the energy of oxidations in the body is ultimately expended in lifting the body during growth.

THE DETOXICATING EFFECT OF THE LIVER OF CATHARTES AURA UPON SOLUTIONS OF β-IMIDAZOLYLETHYLAMIN*

ALLAN C. EUSTIS

(Department of Dietetics and Nutrition, College of Medicine, Tulane University,

New Orleans)

This research was undertaken with an idea of explaining some of the clinical phenomena observed in cases of intestinal toxemia. Many cases are observed by clinicians in which there is very marked indicanuria, but in which there are no subjective symptoms; while other cases may present decided subjective symptoms with only moderate indicanuria.

Most physiologists overlook a very important function of the liver which, to the writer, appears to be its chief function so far as prolongation of life is concerned. We know how soon an animal may die after the institution of an Eck fistula, and yet we meet cases in which the glycogenic (diabetes) and biliary functions (biliary cirrhosis) of this organ are greatly disturbed, or altogether lacking, with little impairment of health for a long time.

The presence of indican in the urine is an example of the results of the detoxicating action of the liver cells upon an intestinal toxin. That such action obtains in the case of other intestinal poisons is shown by the experiments of Ewins and Laidlaw (1) who have shown that p-oxyphenylethylamin, when perfused through the liver of a cat, is broken up into p-oxyphenylacetic acid and urea, which are non-toxic.

The liver of the common turkey buzzard, Cathartes aura, was chosen for the following experiments on account of its well-known fondness for carrion, upon which it apparently thrives. An adult bird, after having been trapped and kept in a cage for 3 days on a diet of fresh raw meat, was killed by a rifle bullet through its head. It was then immediately skinned, care having been taken to avoid

* Proceedings of the Columbia University Biochemical Association, Feb. 5, 1915; BIOCHEM. BULL., 1915, iv, p. 224.

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