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INDUSTRIAL AND ENGINEERING CHEMISTRY
Vol. 25, No. 4
four earning more than $4000. The salaries of almost twofifths of this group (38.8 per cent) are less than $1800, and about the same number (37.9 per cent) earn between $2100
One-third of this group is included in the salary range from $2100 to $2999, and approximately two-fifths (41.9 per cent) have salaries from $3000 to $3999.
and $2999. 10. Fifty-seven per Of thosewith the Ph*D*degree earn $3000 or more, and o d y 10 per cent earn less than $2100.
RECEIVED September 23, 1932. Presented before the Diviaion of Chemical Education a t the 84th Meeting of the American Chemical Society, Denver, COIO.. August 22 t o 26, 1932.
NOTES A N D CORRESPONDENCE Dye-an SIR: The dramatic manner in which a person poisoned by cyanide can be saved through injections of methylene blue has been explained in your recent editorial [IND.ENQ.CHEM.,25, 244 (1933)l on the theory that the administered dye, “being an oxidation-reduction indicator, is able to take up oxygen or give it off readily and thus acts in transferring oxygen to the tissues.” This statement may be easily misinterpreted. I n the first place, neither the oxidant, methylene blue, nor the reductant, leucomethylene blue, contains any oxygen (8). Moreover, there is no authentic evidence, to my knowledge, that the methylene blue system can carry loosely bound oxygen. If interpreted in this sense, as i t is likely to be, the above statement is erroneous. It has been known for some time that cyanide inhibits more or less completely the oxidative processes of the living cell ( 5 ) . More recently it has been demonstrated that the poison produces its characteristic effect on the cell largely by inactivating specific iron-containing respiratory catalysts (cytochrome and hemin-like compounds), the inactivation being reversible (4, 6). The chief function of this type of catalyst seems to be that of activating the molecular oxygen that diffuses in from the air or is carried toward the cell by an oxygen carrier such as oxyhemoglobin. Molecular oxygen itself seems to be too slow-acting to serve the needs of the cell. Granting that this description of the mechanism of cyanide poisoning is correct in its general aspects, treatment for the poisoning involves restoration of the active respiratory catalyst before the cell dies from “internal suffocation.” The dissociation of the catalyst-cyanide complex is too slow because the liberated cyanide must now be metabolized away by the already injured cell mechanism. Administration of fresh respiratory enzyme would be the most logical form of treatment; I do not know if this is practically feasible. Another form of treatment would be to provide the cell with a suitable temporary substitute for the paralyzed catalyst while the latter is being restored. Methylene blue and certain other easily reversible oxidation-reduction systems can be used for this purpose. The oxidants of these systems are all reducible a t the level of potential maintained by the living cell @)-that
Antidote is, they oxidize appropriate cell reductants. This oxidation seems to be performed not by the actual transfer of oxygen but by its electrochemical equivalent of taking on negative electrons or carriers of these electrons. This is, however, but one necessary requirement for the catalyst substitute. Equally important is the need for quick reoxidation of dye reductant back again t o oxidant when exposed to molecular oxygen. There are a number of easily reversible oxidation-reduction systems that meet these specifications-e. g., methylene blue, toluylene blue, pyocyanin (I)-and those that are nontoxic or practically so can serve as temporary substitutes for the paralyzed respiratory enzyme. It also is apparent that this substitute must be able to reach the cell quickly and in sufficient degree to function effectively. On the basis of present knowledge, therefore, one can picture the recovery from cyanide poisoning as follows: The substitute catalyst-for example, methylene blue-mediates in the oxidations necessary for the continuance of cell life during the period in which the natural catalyst is either generated de novo or regenerated by dissociation from its cyanide complex (or both), and the liberated cyanide is metabolized away. It should be evident that the physiological antagonism between methylene blue and cyanide involves no direct interaction between these two substances. I n fact it has been often demonstrated ( 5 ) that cyanide does not interfere appreciably with the oxidation-reduction activity of methylene blue as outlined above. LITERATURE CITED (1) Barron, E. S. G., and Hamburger, M., J. Bid. Chem., 96,299 (1932). (2) Claik, W. M.,Cohen, B., and Gibbs, H. D., P u b . Health Repts., 40, 1131-1201 (1925). (3) Cohen, B., Chambers, R., and Reznikoff, P., J. Gen. Physiol., 11, 585 (1528). (4) Keilin, D., Proc. Roy. Soc. (London), B98,312 (1925). (5) Thunberg, T., Skand. Arch. Physiol., 47,284 (1917). (6) Warburg, O., Saturzvissenschaften, 14, 755 (1926).
BARXETTCOHEN HOPKINS SCHOOL BALTIXORE, MD. March 17, 1933
JOHNS
OF
MEDICINE
Pharmaceutical Industry in Hungary The average annual production of the 15 Hungarian factories engaged in the manufacture of pharmaceuticals and operating at 50 per cent capacity has an estimated value of about $14,000,000. The industry has faced intense competition from German manufacturers. Forty per cent of the industry’s output is in biologicals. Its serums have proved successful in the treatment of livestock diseases. About 80 per cent of the entire production is used in the domestic market, the balance finding a ready sale in the adjacent countries. Domestic consumption has increased in recent years through improved methods of vaccination and inoculation. Despite the development of the domestic production of other pharmaceutical and medicinal preparations, Hun-
gary imports more than it exports. Both imports and exports have shown an increase in the past few years, amounting to $736,000 and $572,000, respectively, in 1931. Serum and vaccine imports were $31,000, against $82,000 in exports. Fully 85 per cent of the imports of finished products come from Germany, with England, Czechoslovakia, and France supplying the remainder. Hungary exports substantial quantities of pharmaceutical products to the Balkan countries and the Near East. Figures for 1932 are not yet available, but they will naturally show a contraction since imports have been placed under a permit system and pengo in payment must be left except in rare cases in Hungary.
