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Notes: Background/aims: Carbobenzoxy-phenylalanyl-methionine (CBZ-Phe-Met), a known inhibitor of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in vitro, has not been evaluated as a topical anti-inflammatory agent in vivo. In order to measure the effect of CBZ-phe-met, one needs a repeat-able, quantitative, easily obtainable standard measurement of the edema formation. In this study, a caliper designed for measuring soft materials was used to evaluate the edema, induced by croton oil on rabbit ears, as well as the effects of CBZ-phe-met.Methods: The model used in this study was croton-induced inflammation on rabbit ears. A caliper for measuring soft materials (European standard DIN 863 part 3, manufactured by TESA Ltd., Renens, Switzerland) was used to evaluate the edema, which is part of the inflammatory effect. The action of CBZ-phe-met and two other anti-inflammatory agents; hydrocortisone and Na-ibuprofen, were compared.Results: CBZ-phe-met 1-5% was found to reduce the edema on rabbit ears induced by croton oil by 15 to 93%. 5% CBZ-phe-met was found to be as effective as 5% Na-ibuprofen and 0.1% hydrocortisone.Conclusion: The caliper for soft materials was found to be suitable for measuring the edema induced by croton-oil, as well as the reducing edema due to anti-inflammatory treatment. It was also found that CBZ-phe-met is a potent topical anti-inflammatory agent in the croton-oil-induced inflammatory model. This may indicate a new approach in the treatment of inflammation.

Notes: Chlorhexidine (CHX) and Hydrogen peroxide (HP) are potent antibacterial agents that are used in controlling dental plaque. However, both agents bear undesired side-effects. We have tested the hypothesis that an antibacterial synergistic effect can occur between the two agents against Streptococcus sobrinus, Streptococcus faecalis and Staphylococcus aureus. We have found that at several combinations of HP and CHX an antibacterial synergistic effect does occur, while at other combinations a non-significant synergism was noticed. No antagonism between the two agents was found in our experimental system. It can be postulated that the mechanism of this synergistic effect is via alteration of the bacterial cell-surface by CHX thereby allowing for an increased amount of HP to penetrate and to react with the intercellular organelles of the bacteria. These results suggest that CHX and HP can be of use in controlling the dental plaque in the oral cavity.

Notes: Abstract A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of “modern” leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies + complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types-monkey kidney epithelial cells and rat beating heart cells. Monolayers of51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic “cocktails” comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn2+ + glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.