Streptococcal cell wall-induced systemic disease. Beneficial effects of trans-bis(5-amidino-2-benzimidazolyl)ethene, a novel, macrophage-directed anti-inflammatory agent.

Abstract	Previously bis(5-amidino-2-benzimidazolyl)methane (BABIM) was identified as a strong inhibitor of the multisystem inflammatory disease induced in Lewis rats by injection of streptococcus group A cell wall-derived peptidoglycan polysaccharide (PG-APS). A BABIM derivative, trans-bis(5-amidino-2-benzimidazolyl)ethene (BBE), has attracted attention because of striking qualitative and quantitative differences in its activities when compared with the parent compound. BBE could control destructive tibial osteitis and necrotizing granulomatous splenitis and hepatitis, regardless if given in a preventive or curative mode. The compound had little effect on synovitis, however. BABIM, on the other hand, was active against synovitis and osteitis, but not against splenic granuloma formation. To be effective, it needed to be applied in a preventive mode. BBE caused a characteristic enlargement of PG-APS-laden splenic and hepatic macrophages suggesting that those cells represent targets of the inhibitor. BBE may be a powerful tool for the study of granulomatous lesions.
Authors	J D Geratz, R R Tidwell, R J Lombardy, J H Schwab, S K Anderle, K B Pryzwansky
Journal	The American journal of pathology (Am J Pathol) Vol. 139 Issue 4 Pg. 921-31 (Oct 1991) ISSN: 0002-9440 [Print] United States
PMID	1928307 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Benzimidazoles Peptidoglycan Polysaccharides bis(5-amidino-2-benzimidazolyl)methane
Topics	Animals Benzimidazoles (therapeutic use) Cell Membrane (metabolism, ultrastructure) Female Granulomatous Disease, Chronic (drug therapy, pathology) Inflammation (chemically induced, drug therapy, pathology) Liver (drug effects, pathology, ultrastructure) Macrophages (drug effects, pathology, ultrastructure) Microscopy, Electron Peptidoglycan Polysaccharides Rats Rats, Inbred Lew Spleen (drug effects, pathology, ultrastructure) Streptococcus (metabolism, ultrastructure) Structure-Activity Relationship

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