R. L. Mayer

Antihistaminic substances in histamine poisoning and anaphylaxis of mice.

The conditions under which mice can be sensitized and the manifestations of sensitization in mice closely simulate those of anaphylaxis in guinea pigs and other animals (Braun, 1 Schultz and Jordan, 2 Ritz, 3 Sarnowski, 4 . Bourden, 5 Weiser, Golub and Hamre 6 ). Active sensitizations can be produced with various protein substances, horse, sheep, cow, guinea pig serum, or egg white; passive sensitizations with immune rabbit serum, antihorse guinea pig serum, antihorse rabbit serum, antipneu-mococcus Type I rabbit serum, etc. The sensitizations are specific and their duration varies from several weeks to several months. Refractoriness occurs after recovery from shock and active desensitization is obtained by The usual desensitization methods. Specific precipitins are formed in mice actively sensitized against egg white with a titer varying from 1:100 to 1:400. From all these facts it has been concluded that the “protein shock” in mice is a true anaphylaxis; they fulfill indeed Doerrs 7 criteria of allergy. The mechanism which ultimately leads to the various anaphylactic manifestations in the different animal species is certainly not the same. The tissue which becomes the principal site of sensitization in guinea pigs is that of the lungs; in rabbits, that of the vascular system; in dogs, that of the liver; etc. The site of sensitization in mice is unknown. The similarity of the symptoms of anaphylactic shock in guinea pigs or dogs to those of histamine poisoning was first recognized by Dale and Laidlaw. 8 The significant increases of the histamine level in the blood during anaphylactic shock in guinea pigs and dogs are strong support for the “histamine theory” of anaphylaxis. It is today commonly accepted that at least in these animal species the antigen-antibody reaction leads to a liberation of histamine or a histamine-like substance, which is the ultimate cause of the anaphylactic shock.

Influence of Pyribenzamine and Antistine upon the Action of Hyaluronidase

Conclusions Experiments are presented which show that (a) hyaluronidase increases the intensity of allergic skin inflammation of the epidermal type and (b) that antihistaminic substances such as Pyribenzamine and antistine counteract the spreading effect of India ink and hyaluronidase, as well as the atters effect upon the allergic skin inflammation. The significance of these findings for the activity of antihistaminics in epidermal sensitizations is discussed.

Virulence in Mice of Colonial Variants of Candida albicans

Summary 1. Several variants isolated from 3 cultures of C. albicans exhibited differences with regard to colonial morphology, microscopic appearance as well as virulence. The smooth colonial type of strain No. 300 proved to be more virulent than the rough colonial form of Strain No. 238. 2. The results of the previous chemotherapeutic tests with Elk-osin in C. albicans infections could not be reproduced in tests performed with the newly isolated variants.

Antituberculous activity of substituted thioureas.

Summary 1. Over 350 thioureas have been prepared in our laboratories and tested for antitubercular activity. 2. A number of disubstituted thioureas have demonstrated considerable protective and therapeutic activities in tuberculous mice and guinea pigs. 3. Little correlation existed between the in vitro and in vivo tuberculostatic action. 4. Many compounds possessed strong antifungal as well as antimycobacterial properties.

The role of the carrier in the formation of complete antigens

Abstract 1.1. Procollagen, like mycobacteria, increases the delayed reactions following sensitization of guinea pigs with picryl chloride or with Old Tuberculin by the parenteral route. Albumin does not exert this effect. 2.2. The effect of tubercle bacilli and lipopolysaccharides isolated from the wax fraction of tubercle bacilli upon the production of sensitizations of the delayed type after intraperitoneal injection is explained by the formation of specific tubercles and consequent formation of fibroid protein, particularly collagen, at sites in the vicinity of the injected hapten, thus enabling the hapten to combine with collagen to form complete antigens containing a carrier of fibroid protein. 3.3. The theory is discussed that the sessile antibody of the delayed type of sensitization is formed by complete antigen with fibroid proteins as carrier, whereas the humoral antibodies of the immediate or anaphylactic type are produced by complete antigen with globular proteins as carriers.

Studies on Inhibition of Tyrosinase

Summary Using a previously described spot-spray technic, more than 400 simple, aromatic compounds were investigated as inhibitors of tyrosinase. 4-Chlororesorcinol inhibited melanin formation from tyrosine, DOPA or epinephrine at a concentration of 10-9; it was thus 20,000 times more potent than resorcinol.

Inhibition of melanin formation in vivo by 4-chlororesorcinol.

Summary The antityrosinase activity of 4-chlororesorcinol, first observed in vitro, is also present in vivo; this substance strongly interferes with pigment formation in the developing dorsal fin of platy fish.

A New Chromosome Stain and Its Relationship to Atypical Cell Proliferation

Conclusion A new chromosome stain is described which is based upon the affinity of nucleoproteids for certain quinone derivatives. The relationship between this stain and the production of atypical epithelial proliferations and cancer produced by aromatic amines is discussed.

Pyribenzamine Aerosol Inhalation and its Influence on Histamine Poisoning and Anaphylaxis

Conclusions 1. PBZ inhaled in the form of an aerosol and in minute amounts, protects guinea pigs against histamine intoxication and anaphylactic shock. This protection is relatively long-lasting. 2. The selective protection which PBZ aerosols confer to the lung tissue permits the observation in guinea pigs of hitherto unrecorded histamine effects. 3. The high activity of PBZ aerosol inhalation and the apparent lack of irritation suggest the possible therapeutic use of PBZ as an aerosol, since it may be predicted that this method of administration produces a lasting therapeutic effect with doses too small to produce undesirable side reactions.

Antituberculosis Activity of Substituted Thioureas. IV. Studies with 4-butoxy-4′-dimethylaminothiocarbanilide (Su 1906)

Summary 1. In vitro resistance to 4-butoxy-4′-dimethylamino thiocarbanilide (Su 1906) develops at an appreciably slower rate than that developed to streptomycin, PAS, or isoniazid. 2. A combination of a sub-inhibiting concentration of Su 1906 with either streptomycin or isoniazid, considerably retards the emergence of streptomycin or isoniazid resistant strains. 3. A state of cross-resistance exists between Tibione and Su 1906.