Use of the reversed passive arthus reaction as a test for anti-inflammatory agents

The immune complex-induced reversed passive Arthus (RPA) reaction in the rabbit has been investigated as a screening test for detecting anti-inflammatory agents dotentially more effective in the treatment of rheumatoid arthritis than those presently available. RPA lesions, characterized by edema, erythema, and hemorrhage, were elicited by intravenous injections of bovine serum albumin (BSA) followed by intradermal injections of rabbit anti-BSA antiserum. The anti-edema activities of compounds (mg quantities required for testing) were evaluated after their administration by the intradermal route (compounds admixed with antiserum) as well as by the intraperitoneal route. Of 14 reference anti-inflammatory agents tested by the intradermal screening procedure, only aurothioglucose and chloroquine were inactive. Other pharmacologically active compounds (e.g. antihistamines, anti-complement agents, cytotoxic-immunosuppressives) were also evaluated after their intradermal administration. Protoporphyrin, phloretin, and hexadimethrine bromide (Polybrene^®) were active. When whole antiserum, or the antibody fraction of the serum, was used to eliminate nonspecific edema, intraperitoneally administered reference agents were found to be effective in the RPA test.     

Effects of the synthetic enkephalin analogue FK 33-824 on pain threshold and pain tolerance in man

Natural enkephalins exert weak and transitory analgesic effects. The synthetic enkephalin, FK 33-824 (FK), is less susceptible to metabolic breakdown and produces long-lasting analgesia in animals. The present studies examined the effects of FK on threshold and tolerance of electrically evoked pain in man under double blind conditions. 1.0 mg FK given intramuscularly (saline control) increased tolerance significantly without affecting the pain threshold, but also produced vasodilatation and feelings of oppression and heaviness (study I). In study II, where 50 mg betazole was employed as "placebo" because of its vasodilatatory effects, 1.0 mg FK increased pain tolerance significantly more than 0.25 mg FK while the threshold remained unchanged. Self-ratings of activation and well-being decreased; those of oppression increased, as did reaction time, equally after 0.25 and 1.0 mg FK but were not altered by betazole. In conclusion, 1.0 mg FK i.m. increases tolerance but not perception of pain, thus mimicking the analgesic effects of morphine.     

Characteristics of Folic Acid-binding Protein in Folate-deficient Serum

Folate-deficient serum contains a specificfolic acid-binding protein (FABP) that has arapid association and slow dissociation ratefor the binding of ³H-pteroylglutamic acid(³H-PGA). FABP is also present in normalserum but in lesser amounts. The molecular weight of FABP is less than 100,000and may represent more than one protein.FABP elutes as a beta globulin and isrecovered in the transferrin band region inpolyacrylamide gel electrophoresis. FABPbinds oxidized folyl-, mono-, and polyglutamates in preference to reducedfolates. FABP retards the delivery anduptake of ³H-PGA into HeLa cell monolayer cultures. The characteristics of FABPsuggest it to be a membrane-derived intracellular folate storage protein and perhapsan important regulator of folate uptake intothe cell and a storage site for folyl polyglutamates. The characteristics of serumFABP suggest it to be similar to beta lactoglobulin (the folate-binding protein isolatedfrom cow’s milk).

Submitted on May 17, 1972 Revised on December 12, 1972 Accepted on January 7, 1973