IMMUNOLOGICAL PROPERTIES OF 7432-S, A NEW CEPHALOSPORIN ANTIBIOTIC AGENT FOR ORAL USE
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The immunological properties of 7432-S, a newly developed cephalosporin antibiotic agent for oral use, were examined in reference to cefaclor (CCL).<BR>1) Immunogenicity in guinea pigs: No antibody response to 7432-S was shown by active systemic anaphylaxis, 24-h passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA), when guinea pigs were immunized with multiple oral or intramuscular administrations of unconjugated 7432-S. However, weak but definite antibody production was detected by the most sensitive assay, ELISA, in a few animals which had been immunized with repeated intraperitoneal injections of 7432-S emulsified with Freund's complete adjuvant (FCA). Under the same immunizing conditions, CCL did not produce antibodies. However, making reference to our previous finding that cefalothin (CET) and cefmetazole (CMZ) induced much more potent immune responses under the same conditions, 7432-S is less immunogenic than these commercial antibiotic preparations.<BR>2) Immunogenicity in mice: When C 57 BL/6 J mice were injected with FCA emulsion containing 7432-S, CCL, or ceftizoxime (CZX), antibody response was detected to each antibiotic agent by means of ELISA but not by rat PCA. Similar results were obtained in C3H/He mice which had been immunized to 7432-S, CCL or CZX with the exception of production of anti-CZX IgE antibody in only one animal.<BR>3) Hypersensitivity-eliciting antigenicity: Oral and intravenous challenge with unconjugated 7432-S to guinea pigs presensitized actively with 7432-S-BGG (BGG: bovine γ-globulin) conjugate did not elicit systemic anaphylaxis. Similarly, challenge with plain 7432-S did not provoke PCA in guinea pigs which had been locally sensitized with anti-7432-S-BGG serum. Also, 7432-S as well as CCL and CZX did not elicit PCA in rats which had been sensitized passively with mouse antiserum to the homologous antibiotic-BGG conjugate. These results indicate that 7432-S does not have hypersensitivity-eliciting antigenicity.<BR>4) Immunological cross-reactivity of 7432-S hapten with other β-lactam antibiotic haptens: Immunological cross reactivity of 7432-S with six other β-lactam antibiotics, i.e, CCL, CZX, penicillin G (PCG), CET, CMZ and latamoxef (LMOX), was examined by means of 4-h PCA in guinea pigs and 24-h PCA in rats mediated by guinea pig IgG<SUB>1</SUB>, and mouse IgE antibodies, respectively. Antisera to antibiotic-BGG conjugates were used as the antibody preparations and antibiotic-GpSA (GpSA: guinea pig serum albumin) conjugates were employed as elicitors. In guinea pig PCA, 7432-S hapten cross-reacted with CZX hapten but not at all with the other antibiotic haptens. In rat PCA, however, no cross reactivity was observed between 7432-S and other haptens.<BR>5) Activity to produce <I>in vitro</I> direct Coombs' reaction: The activity of 7432-S to produce direct Coombs' reaction was compared with those of CET, CMZ, PCG and LMOX using human red blood cells. CET and PCG produced a positive reactions at the final concentrations of 2.5 to 10 mg/ml and 20 to 40 mg/ml, respectively. However, 7432-S as well as CMZ and LMOX did not cause a positive reaction even at 40 mg/ml.
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