Streptococcal Infection In Mice Research Articles

RATIONAL THERAPY IN ACUTE OTITIS MEDIA

The literature is diffusely infiltrated with suggestions concerning the therapy of acute otitis media. The subject is a time-honored one and justifiably so. Treatment of the condition has radically changed during the past few years, since the advent of the various sulfonamide compounds. The monumental work of Domagk, who demonstrated that prontosil 1 exerted a selective action on streptococcic infections in mice, cannot be minimized. 2 Kopetzky 3 said: ... The literature is replete with clinical material which adds little to the sum of knowledge, and one is puzzled even to find the raison d'etre for some of the case reports, since they settle no questions and too often only reiterate accepted facts and customary procedures. Almost phenomenal results in all cases of acute and even subacute otitis media have been obtained with adequate and carefully supervised use of sulfonamide compounds (see the accompanying table). It is obvious that the patient

Studies with Sulfabenamide. I. Blood Levels and Elimination in the Urine of Uninfected Rabbits

pounds possess low toxicity, and appear to be effective therapeutically against streptococcal infections in mice. On the basis of experiments with mice and comparison with sulfanilamide23 one of the most promising of these compounds is p-n-caproylaminobenzenesulfonhydroxamide, CH3(CH2)4CONHC6H4S02NHOH. This compound has been designated by the term sulfabenamide.4 Our preliminary experiments with mice infected with a virulent strain of hemolytic streptococcus and treated with sulfanilamide and with sulfabenamide confirmed the results referred to above.23

Prof. G. Domagk

PROF. GERHARD DOMAGK, who has been awarded the Nobel Prize for Physiology and Medicine for 1939, is the pathologist to the medical and biological research laboratories of the Bayer Company of Elberfeld. Domagk was comparatively little known, beyond the range of those familiar with the work of that institution, until, nearly five years ago, homade a discovery which has led to one of the most rapid and remarkable advances on record in therapeutic science and practice. The late Paul Ehrlich began his researches in chemotherapy with the attempt to find substances which would deal directly, as disinfectants, with bacterial infections in the living body. He, like many others who have followed, abandoned what seemed to be a hopeless quest, and turned his attention to the discovery of chemothera-peutic remedies for infections due to protozoa and spirochætes, the most important outcome being the discovery of salvarsan. It had almost come to be assumed that bacterial infections were beyond the reach of chemotherapy, though Morgenroth's ‘Optochin’ and its allies had given some hope of eventual success. Domagk appears to have examined a series of dyes for their action on streptococcal infoctions in the living body, irrespective of a lack of disinfectant properties outside it. In January 1935 he described the remedial effect on streptococcal infections in mice of a red dye, named ‘Prontosil’, an amide of chrysoidine, which had been prepared by Mietzsch and Klarer, chemists on the staff of the Bayer Company. Some confirmatory clinical results were obtained, but the first organized trial of ‘Prontosil’ on a uniform series of cases of streptococcal infection in man was made by Colebrook in Great Britain.

MENINGITIS CAUSED BY PNEUMOCOSSUS TYPE III

A new type of therapeutic agent effective against certain virulent bacterial infections was elaborated after many years of pioneer work on the chemical properties of azo dyes. 1 Domagk 2 in 1935 reported on the use of the original prontosil in the treatment of experimental streptococcic infections in mice. He found that a sulfonamide group in certain azo dyes caused them to protect or cure mice infected with fatal doses of hemolytic streptococci. The most effective of these dyes are 4-sulfamido-2'-4'-diaminoazobenzene hydrochloride (the original prontosil) and the disodium salt of 4-sulfamidophenyl-2'-azo-7'-acetylamino-1'-hydroxynaphthalene-3', 6'-disulfonic acid (the compound known as prontosil soluble and then as prontosil and now to be called neoprontosil). A short time later the Trefouels, Nitti, Bovet and Fourneau 3 noted that paraaminobenzenesulfonamide constitutes the active fraction of both the prontosils; they then synthesized paraaminobenzenesulfonamide, later to be known as sulfanilamide. Their observations were confirmed and elaborated by Goissedet, Despois,

MODE OF ACTION, CLINICAL USE AND TOXIC MANIFESTATIONS OF SULFANILAMIDE

In this communication we will report further on the mode of action of in the treatment of infections and will discuss methods of therapy with and the toxic manifestations which sometimes arise during the course of therapy. THE MODE OF ACTION OF SULFANILAMIDE A year ago we 1 reported that experimental evidence shows that bacteriostasis is the only demonstrable factor in the process which leads to the control of Clostridium welchii infection in mice treated with sulfanilamide and that observations made by us in streptococcic infections in mice treated with also could be interpreted as evidence that bacteriostasis plays a role in the control of this type of infection. In our preliminary report 2 we noted that in a concentration of 1: 10,000 exerted a definite bacteriostatic effect in broth cultures inoculated with small numbers of beta hemolytic and alpha and gamma

SULFANILAMIDE AND SERUM IN THE TREATMENT AND PROPHYLAXIS OF SCARLET FEVER

In 1935 Domagk 1 showed that prontosil 2 had a marked protective and therapeutic value in experimental streptococcic infections in mice. This observation has been confirmed by numerous investigators. The drug also has a beneficial effect on similar infections in other animals and in man. Shortly after Domagk's discovery, Trefouel and his co-workers 3 showed that prontosil was broken down in the tissues to triaminobenzene and para-aminobenzene sulfonamide. The latter compound was believed by them to be the effective component of prontosil. Recently numerous derivatives of the drug have been synthesized, but the estimation of the effectiveness of many of them requires further investigation. The mode of action of sulfanilamide and its derivatives is still the subject of much conjecture. Since prontosil has little or no bactericidal action in vitro. Domagk believed that enhancement of phagocytosis of the streptococci by the leukocytes explained its beneficial effect. Levaditi and Vaisman 4

INFLUENCE OF SULFANILAMIDE ON INFECTED SINUSES OF RABBITS: CHEMICAL AND MICROSCOPIC STUDIES

According to the numerous reports which have appeared in the literature during the past year, sulfanilamide (paraaminobenzenesulfonamide) therapy has continued to hold a prominent place in the successful treatment of pneumococcic, 1 meningococcic 2 and gonococcic 3 infections and others, of a much more remote cause, as well as those caused by hemolytic streptococci. 4 The fact that the immediate toxic effects have been relatively few has been an added impetus to the more extensive administration of sulfanilamide. Some toxic reactions have been easily compensated for by the withdrawal of the drug, while others, of a more serious nature, such as acute hemolytic anemia 5 and agranulocytosis, 6 are probably attributable to idiosyncrasies, according to Marshall and his co-workers. 7 Many theories have been advanced to explain the mode of action of the drug. Domagk, 8 as the result of experiments in the treatment of experimental streptococcic infections in mice, reported that the phagocytosis of the streptococci by

Derivatives of p-aminobenzenesulphonamide in the treatment of streptococcal infection in mice

Derivatives of <i>p</i>-aminobenzenesulphonamide in the treatment of streptococcal infection in mice