ACTIVITY OF PENICILLIN ESTERS

331 I wish t6 thank’Prof. Samson Wright and Dr. D. Slome for much help and encouragement. The expenses of this research were partially defrayed by a grant from the Medical Research Council to Prof. Samson

Wright. ,,

REFERENCES

Breedis, C., Flory, C. M., Furth, J. (1943) Arch. Path. 36, 402. Courtois J., Biget, P. (1943) Bull. Soc. Chim. biol. 25, 103. Demuth, F. (1925) Biochem. Z. 159, 415. Dmochowski, A. (1933) C.R. Soc. Biol. Paris, 113, 956. Folin, O., Denis, W. (1915) J. biol. Chem. 22, 305. Gutman, A. B. (1942) J. Amer. med. Ass. 120, 1112. Gutman, E. B. (1938) Proc. Soc. exp. Biol., N.Y. 39, 529. —

—

—

(1941) Endocrinology, 28, 115.

King, E. J., Armstrong, A. (1934) Canad. med. Ass. J. 31, 376. Wood, E. J., Delory, G. E. (1945) Biochem. J. 39, 4. Kutscher, W., Wolbergs, H. (1935a) Naturwissenschaften, 23, 558. (1935b) Z. physiol. Chem. 236, 237. Wörner, A. (1936) Ibid, 239, 109. Rabaté, J., Courtois, J. (1941) Bull. Soc. Chim. biol. 23, 190. —

— —

—

Scott, W. W., Huggins, C. (1942) Endocrinology, 30, 107. Theis, R. C., Benedict, S. R. (1924) J. biol. Chem. 61, 67. Waldschmidt-Leitz, E., Nonnenburg, H. (1935) Naturwissenschaften, 23, 164. Wilmer, H. A. (1944) Arch. Path. 37, 227. Wolbergs, H. (1936) Z. physiol. Chem. 238, 107.

Preliminary

Communication

ACTIVITY OF PENICILLIN ESTERS

AMONG the various procedures for prolonging the time during which penicillin remains in the blood-stream at a therapeutic level, with an accompanying reduction in the rate of urinary excretion, the use of water-insoluble penicillin esters has been suggested. I have made a detailed study of the methyl and benzyl esters of " pure " penicillin, having an activity of 1500 f.-u.1/mg. The details of this work will be published elsewhere in full 1 ; meanwhile the general conclusions may be of interest to

penicillin

users.

I find that some

rats, and

guineapigs,

the hydrolyses in 10 minutes.

of animals, have in their sera

species

including mice, an

esterase that

methyl and benzyl esters of penicillin This enzyme, or complex of enzymes, is

absent from the

of rabbits and mail. When the into the rabbit or man no therapeutic effect is exerted. No penicillin can be detected circulating in the blood of rabbits or men during periods esters

sera

injected

are

between 1 and48 hours after injection. Furthermore, it appears that the ester, though it exerts no antibacterial effect, is destroyed in the body, for it cannot be found in the blood or urine of rabbits and men after injection. On the other hand, the enzymatic hydrolysis of these esters in mice, rats, and guineapigs, with the resulting liberation of penicillin, confers on them an antibacterial action of the ,same order as that of corresponding quantities of the free

- antibiotic.

,

These conclusions have consequences both in applied therapeutics and in laboratory technique. It is clear that the esters cannot have any value as compounds for prolonging the penicillin effect when injected into man, because, not being hydrolysed, they have no antibacterial effect at all. On the other hand, the existence of a penicillin esterase in the sera of mice, rats, and guineapigs makes these sera, particularly those of guineapigs, useful agents for investigating the effect of the esters in various species of animals. Incubation at 37°C with guineapig serum, for example, causes liberation from the methyl and benzyl of free penicillin, which can then be estimated in the usual manner. This method gives a convenient and quick method of detecting penicillin esters in different organs and body fluids, and should also prove useful in testing therapeutic

estexs

.

agents. Glaxo Laboratories Ltd., Greenford, Middlesex. 1. Ungar, J.

J. UNGAR.

Brit. J. exp. Path. (in the press).

Medical Societies ASSOCIATION OF CLINICAL PATHOLOGISTS THE association’s annual meeting was held in London on Jan. 24 and 25, under the chairmanship of Dr. J. G. GREENFIELD. The Interpretation of Blood-sugar Levels in Children was discussed by Dr. J. L. EMERY, who showed cases of coeliac disease with clinical hypoglycaemia despite normal fasting blood-sugar levels. The pallor and sweating are relieved by glucose without a rise in the blood-sugar, and adrenaline also relieves the symptoms. Clinical manifestations should be recognised as real evidence of hypoglycaemia irrespective of the blood-sugar content, especially since symptoms may occur, even with a rising blood-sugar, following administration of insulin. Dr. N. F. MACLAGAN described a modification of the .Lange colloidal gold curve using buffered solutions. The advantages of buffered solutions are that they are more .

exactly reproduced and give more dependable results, they are unaffected by traces of acid and alkali and because false positives are less common. The standard ten tubes are unnecessary since it is only the precipitation in the lower dilutions which indicates globulin increase. Dr. B. E. TOMLINSON, speaking on the chronic appendix, said that there was no appreciable difference between the appendices in 100 surgical cases and those in 100 bodies following sudden death. In the surgical cases, however, localised inflammatory changes were seen in the internal muscle layer ; these suggested a retrogressing because

lesion.

Local

eosinophils

of fibrosis and local collections of demonstrated in the muscle coats ; but

areas

were

as far as the mucosa was were often in the

concerned eosinophil counts controls than in the surgically higher removed appendices. He concluded with a plea for more exact pathological appraisal of the surgically removed appendix. Dr. J. T. DUNCAN described the widespread lesions which may be found in torula meningitis. Infection, he suggested, usually takes place via the tonsil or by trauma of the skin, and the organism, Cryptococcus neoformans, has a predilection for the central nervous system and the lungs. It is hard to recognise this organism unless it is properly stained, preferably by muci-carmine. There are probably more cases of torula meningitis than is appreciated, for with a careful look-out they are identified often. Dr. V. D. ALLISON and Miss B. HOBBS discussed the epidemiology of pemphigus neonatorum from observation of 200 cases seen in one large and two small epidemics, using serological typing of Staphylococcus pyogenes. This showed that the sources of infection are the upper respiratory tract and skin of carriers. Carriers are commoner among nurses than the general public ; and one series of cases originated from a carrier whose task it was to fold clean napkins in a laundry. It is important not to incriminate an attendant until it has been proved that the serological type found in her agrees with that causing the epidemic. It may be worth applying penicillin to the anterior nares of chronic tonsil carriers. Dr. J. G. GREENFIELD, reviewing the causes of cerebral abscess, emphasised the importance, in the differentiation from meningitis, of estimating the sugar in the cerebrospinal fluid ; this is early reduced with meningitis, while with abscess it usually remains normal until meningitis supervenes. Usually the cerebrospinal fluid is clear ; the cell-count in his cases varied from 4 to 800 per c.mm., with lymphocytes predominating ; and protein varied from 10 to 200 mg. per 100 ml. The organisms were very variable : of 45 cases, 15 were due to staphylococcus, 10 to anaerobic streptococcus, 10 to fusiform bacillus,

fairly

.