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Notes: Background: Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997).Objectives: The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design).Material and methods: One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI 〈 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP.Results:  All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p 〈 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP 〈 15 or 〈 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p 〈 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using 〉 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p 〈 0.05).Conclusions: These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.

Notes: Abstract Histatins, histidine-rich proteins found within parotid and submandibular secretions, are a novel class of endogenous peptides with antimicrobial properties. This masked, randomized, placebo-controlled preclinical investigation examined the effect of 3 topical histatins on the development of plaque and gingivitis in beagle dogs. 16, female, 1-year-old beagles were brought to optimal gingival health by mechanical scaling and polishing followed by rigorous daily tooth brushing. At the conclusion of this pretreatment period, dogs were randomly divided into 4 groups for the application of test formulations, and were placed on a plaque-promoting diet, Test agents included 3 synthetic salivary histatins (histatin 5, P-113 and P-113D) which were incorporated in hydroxypropyl methylcellulose gel at a concentration of 0.125%, and a placebo, or negative control, which was the gel vehicle alone. Throughout the 10-week treatment period, test formulations (2.0 ml) were applied 2xdaily to all premolar teeth using a Monojet syringe. Plaque formation and gingival inflammation were assessed using the plaque (PI) and gingival (GI) indices on days 0, 7, 14, 21, 28, 42, 56 and 70. Furthermore, bleeding to probing was recorded as a percent of sites (%BOP) and according to the modified sulcus bleeding index (mSBI). Comparisons among groups and between group pairs (active versus placebo) were made with Kruskal-Wallis tests with the average of data over the interval, days 14–42, being the primary focus of the analysis. From baseline to day 7, all groups expressed similar indices. Thereafter, overall significant differences among the groups were noted at day 42 for PI, at days 21, 28, 42 and 70 for GI, and at days 14 and 28 for %BOP (p〈0.05). In particular, beagles treated with P-113 demonstrated significantly lower PI scores at day 42 (p〈0.05), significantly lower GI scores from days 21 through 42 (〈0.05), and significantly lower %BOP scores at days 14 and 28 (p〈0.05) compared to beagles treated with placebo. Beagles treated with P-113D exhibited significantly lower GI at day 42 compared to the placebo (p〈0.05). For the primary analysis conducted over the midtreatment interval (days 14–42), significant differences were detected for all parameters except mSBI (p〈0.05). Accordingly, significantly lower PI scores were found for P-113, lower GI scores for P-113 and P-113D, and lower %BOP for P-113 and P-113D compared to placebo (p〈0.05). These data indicate that in the beagle model, salivary histatins, P-113 and P-113D, topically applied, can significantly reduce clinical signs of plaque formation and gingival inflammation.

Notes: Addition of rheumatoid factor to cultures of human lymphocytes preincubated with substimulating amounts of rabbit anti-human lymphocyte antibody caused stimulation, while addition to lymphocytes preincubated with anti-HL-A or anti-human γ-chain antiserum had no effect. Neither was there any stimulatory effect on adding pepsin agglutinator, i.e. an antibody to the pepsin site of γG, to lymphocytes preincubated with pepsin-digested γG from anti-lymphocyte or anti-HL-A antiserum. The different results obtained in the various systems may partly be due to differences in the distribution of antigens on the lymphocyte membrane and partly to the lack of heterospecificity of pepsin agglutinator.