effects of scn−/h2o2 combinations in dentifrices on plaque and gingivitis

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J Clin Periodontol 2001; 28: 270–276 Copyright C Munksgaard 2001 Printed in Denmark . All rights reserved ISSN 0303-6979 Michael Rosin 1 , Thomas Kocher 1 and Axel Kramer 2 Effects of SCN ª /H 2 O 2 1 Department of Operative Dentistry, Periodontology and Paediatric Dentistry, 2 Institute of Hygiene and Environmental combinations in dentifrices Medicine, University of Greifswald, Germany on plaque and gingivitis Rosin M, Kocher T, Kramer A: Effects of SCN ª /H 2 O 2 combinations in dentifrices on plaque and gingivitis. J Clin Periodontol 2001; 28: 270–276. C Munksgaard, 2001. Abstract Objectives: A 10-week, double-blind, placebo-controlled clinical study on 140 male subjects was conducted to determine the effect on plaque and gingivitis of 5 dentifrices containing various thiocyanate (SCN ª )/hydrogen peroxide (H 2 O 2 ) combinations. Materials and Methods: The dentifrices consisted of a gel base without any deter- gents or abrasives (placebo, group A) to which SCN ª and/or H 2 O 2 were added as follows: 0.1% SCN ª (group B), 0.5% SCN ª (group C), 0.1% SCN ª / 0.1% H 2 O 2 (group D), 0.5% SCN ª /0.1% H 2 O 2 (group E) and 0.1% H 2 O 2 (group F). A baseline examination was performed in which the Silness and Löe Plaque Index (PI), the Mühlemann and Son Sulcus Bleeding Index (SBI), and the amount of gingival crevicular fluid (GCF) were recorded using the Periotron 6000 on teeth 16, 12, 24, 36, 32, and 44. The subjects were randomly assigned to either the pla- cebo group (nΩ40) or one of the test groups (nΩ20) and used their respective dentifrices over a period of 8 weeks. Finally, each group used the placebo for another 2 weeks (wash-out). Re-examinations were performed after 1, 4, and 8 weeks and the 2-week wash-out period employing the clinical parameters used at baseline. Intragroup changes were analyzed with the Wilcoxon signed-ranks test, using the baseline and wash-out points as references. The Mann-Whitney U test was used for comparisons between the treatment groups and the placebo group. Results: At the 8-week examination, the plaque index in group E (pΩ0.017) and group F (pΩ0.032) was lower than in the placebo group. The Sulcus Bleeding Index in group F after 1 week was increased (pΩ0.023) and the SBI in group E after 8 weeks was reduced (pΩ0.047) as compared to the placebo group. Key words: thiocyanate; hydrogen peroxide; Conclusion: The results demonstrated that a dentifrice containing 0.5% SCN ª gingivitis; plaque and 0.1% H 2 O 2 but no detergents or abrasives inhibited plaque and decreased gingivitis. Accepted for publication 24 April 2000 The ro ˆ le of dental plaque as the major factor in the etiology of diseases such as caries, gingivitis, and periodontitis has been clearly recognized for many years (Löe et al. 1965, Lindhe et al. 1975, Ax- elsson et al. 1991). However, only a small percentage of patients has the ability and motivation to effectively re- move plaque on a regular basis (De La Rosa et al. 1979). Therefore, supple- mentation of mechanical brushing with effective antimicrobial agents in tooth- pastes would promote the control of dental plaque (Frandsen 1986, Mandel 1988). However, the addition of anti- biotics is not acceptable due to poten- tial hazards of the development of anti- microbial resistance and undesired shifts in the oral ecology. With chemical agents, it is difficult to achieve concen- trations high enough to have a clinical antiplaque effect without side effects like taste alterations, discoloration of the teeth and tongue (Heasman & Seymour 1995), and the risk of microtoxic long-term side effects. There is also the risk of losing the initial effect with increasing duration of use (Fine 1985). Therefore, the enhancement of sal- iva’s natural antimicrobial systems could be a useful supplement in main- taining oral health. The concept which has been pursued the longest is that of supporting the peroxidase system. Per- oxidase enzymes catalyze the oxidation

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Page 1: Effects of SCN−/H2O2 combinations in dentifrices on plaque and gingivitis

J Clin Periodontol 2001; 28: 270–276 Copyright C Munksgaard 2001Printed in Denmark . All rights reserved

ISSN 0303-6979

Michael Rosin 1, Thomas Kocher 1 andAxel Kramer 2Effects of SCNª/H2O2 1Department of Operative Dentistry,Periodontology and Paediatric Dentistry,2Institute of Hygiene and Environmentalcombinations in dentifrices Medicine, University of Greifswald, Germany

on plaque and gingivitisRosin M, Kocher T, Kramer A: Effects of SCNª/H2O2 combinations in dentifriceson plaque and gingivitis. J Clin Periodontol 2001; 28: 270–276. C Munksgaard,2001.

AbstractObjectives: A 10-week, double-blind, placebo-controlled clinical study on 140male subjects was conducted to determine the effect on plaque and gingivitis of 5dentifrices containing various thiocyanate (SCNª)/hydrogen peroxide (H2O2)combinations.Materials and Methods: The dentifrices consisted of a gel base without any deter-gents or abrasives (placebo, group A) to which SCNª and/or H2O2 were addedas follows: 0.1% SCNª (group B), 0.5% SCNª (group C), 0.1% SCNª/ 0.1%H2O2 (group D), 0.5% SCNª/0.1% H2O2 (group E) and 0.1% H2O2 (group F). Abaseline examination was performed in which the Silness and Löe Plaque Index(PI), the Mühlemann and Son Sulcus Bleeding Index (SBI), and the amount ofgingival crevicular fluid (GCF) were recorded using the Periotron 6000 on teeth16, 12, 24, 36, 32, and 44. The subjects were randomly assigned to either the pla-cebo group (nΩ40) or one of the test groups (nΩ20) and used their respectivedentifrices over a period of 8 weeks. Finally, each group used the placebo foranother 2 weeks (wash-out). Re-examinations were performed after 1, 4, and 8weeks and the 2-week wash-out period employing the clinical parameters used atbaseline. Intragroup changes were analyzed with the Wilcoxon signed-ranks test,using the baseline and wash-out points as references. The Mann-Whitney U testwas used for comparisons between the treatment groups and the placebo group.Results: At the 8-week examination, the plaque index in group E (pΩ0.017) andgroup F (pΩ0.032) was lower than in the placebo group. The Sulcus Bleeding Indexin group F after 1 week was increased (pΩ0.023) and the SBI in group E after 8weeks was reduced (pΩ0.047) as compared to the placebo group.

Key words: thiocyanate; hydrogen peroxide;Conclusion: The results demonstrated that a dentifrice containing 0.5% SCNªgingivitis; plaque

and 0.1% H2O2 but no detergents or abrasives inhibited plaque and decreasedgingivitis. Accepted for publication 24 April 2000

The role of dental plaque as the majorfactor in the etiology of diseases such ascaries, gingivitis, and periodontitis hasbeen clearly recognized for many years(Löe et al. 1965, Lindhe et al. 1975, Ax-elsson et al. 1991). However, only asmall percentage of patients has theability and motivation to effectively re-move plaque on a regular basis (De LaRosa et al. 1979). Therefore, supple-mentation of mechanical brushing witheffective antimicrobial agents in tooth-

pastes would promote the control ofdental plaque (Frandsen 1986, Mandel1988). However, the addition of anti-biotics is not acceptable due to poten-tial hazards of the development of anti-microbial resistance and undesiredshifts in the oral ecology. With chemicalagents, it is difficult to achieve concen-trations high enough to have a clinicalantiplaque effect without side effectslike taste alterations, discoloration ofthe teeth and tongue (Heasman &

Seymour 1995), and the risk ofmicrotoxic long-term side effects. Thereis also the risk of losing the initial effectwith increasing duration of use (Fine1985).

Therefore, the enhancement of sal-iva’s natural antimicrobial systemscould be a useful supplement in main-taining oral health. The concept whichhas been pursued the longest is that ofsupporting the peroxidase system. Per-oxidase enzymes catalyze the oxidation

Page 2: Effects of SCN−/H2O2 combinations in dentifrices on plaque and gingivitis

SCNª/H2O2 combinations 271

of thiocyanate (SCNª) to OSCNª,02SCNª and possibly 03SCNª and tohypothiocyanous acid (HOSCN)(Thomas 1981), which are effective anti-microbial agents (Mansson-Rahemtullaet al. 1987, Lumikari et al. 1991a). Thelimiting component for the productionof the oxidation products of SCNª inwhole saliva is hydrogen peroxide(H2O2) (Pruitt et al. 1982). An enhance-ment of the peroxidase system in vivowas demonstrated by adding smallamounts of H2O2-generating enzymesto toothpastes or mouthrinses (Mans-son-Rahemtulla et al. 1983, Lenander-Lumikari et al. 1993). This principle isthe basis for a commercially availabletoothpaste (Rotgans & Hoogendoorn1979, Midda & Cooksey 1986). Theclinical effects of that toothpaste havebeen controversial (Tenovuo et al.1991).

Little attention has been paid to thio-cyanate (SCNª). However, SCNª is notmerely a co-factor in the peroxidase sys-tem; it also acts as a ubiquitous vit-aminoid (Kramer et al. 1998) with thefollowing main effects:O Promotes unspecific and specific

resistance mechanisms (e.g., phago-cytosis, IgG anitbody formation, stimu-lation of leucocyte migration), provenin infection models with experimentalanimals (Jülich et al. 1973, 1974, 1975,Apitzsch et al. 1985, Kramer et al.1987) and in hepatitis-B immunizationsin humans (Jülich et al. 1997).O Protective effect against toxic and

mutagenic agents (e.g., in animal ex-periments with irritation, hepatosis,gastritis, and mammary tumors) (Na-gasawa et al. 1980, Kramer et al. 1983,Jülich et al. 1984, Whitehouse & Rains-ford 1983, Kramer & Weuffen 1996)O Promotes regenerative processes

(wound healing, hair formation, UVerythema) (Kramer 1985, 1990, 1996,Koch 1989, Töfke et al. 1991).

Additionally, via the enzymes lacto-peroxidase (LPO), myeloperoxidase(MPO), and eosinophile peroxidase

Table 1. SCNª and H2O2 concentrations inthe toothpastes in different groups

Tube A Tube B

group A (placebo) – –group B 0.1% SCNª –group C 0.5% SCNª –group D 0.1% SCNª 0.1% H2O2

group E 0.5% SCNª 0.1% H2O2

group F – 0.1% H2O2

Fig. 1. Clinical trial outline.

(EPO), SCNª is able to detoxify oxygenradicals (Kramer & Böhland 1996).Thus, it has an important protectivefunction under toxic influences, in pro-cesses of aging, and in inflammations(for review, see Kramer & Böhland(1996)).

Therefore, in terms of the aspectslisted above, we put forth the hypothesisthat SCNª concentrations which liehigh above the physiological salivaryconcentration have a positive effect ongingival health and also develop anantiplaque effect via synergistic interac-tions with the antibacterial systems ofsaliva. The aim of this study was thusto evaluate the effects of various SCNª/H2O2 combinations in toothpastes onplaque and gingivitis scores.

Material and MethodsSubjects

140 male subjects aged between 18 and30 years (mean 23 years) were recruitedafter having given informed writtenconsent. 21 subjects were patients and17 subjects were staff members of theUniversity Dental Clinic of Greifswald.102 subjects were students at Greifs-wald University, 35 of whom were den-tal students. In order to participate inthe study, the subjects had to meet thefollowing criteria:– non smoker,– a minimum of 12 teeth in each jaw,– no probing depths >6 mm,– negative history of antibiotic ther-

apy or administration of antiseptics6 months prior to the examination,

– no systemic illness known to affectoral health,

– no medication with a possible effect

on the oral microflora or on oralhealth.

Study design

The study was conducted as a doubleblind, randomized, placebo-controlled,10-week clinical trial with parallelgroup design. The 140 subjects were as-signed randomly to one placebo andfive test groups (Table 1). At baseline,the dentifrices (described below) andnew toothbrushes (ElmexA multi-effect,soft/medium, GABA AG, Therwil,Switzerland) were distributed to thesubjects. They were asked to brush theirteeth as they usually do and to refrainfrom using any other oral hygiene prod-ucts and from chewing gum for the dur-ation of the experiment. The groupsused their respective toothpastes twotimes per day, in the morning and in theevening, over a period of 8 weeks. Afterthe 8-week examination, every groupused the placebo combination for an-other 2 weeks (Fig. 1). The investigatorswere informed about this wash-outperiod, but the patients were not. Clin-ical examinations were performed atbaseline and after 1, 4, and 8 weeks, andafter the wash-out period with the pla-cebo. The baseline examination in-cluded a full-mouth recording of the

Table 2. Correlation coefficients r for SBIand PI assessed in the whole mouth (wholeSBI, whole PI) and on control teeth 16, 12,24, 36, 32 and 44 (SBI control, PI control)on the 140 subjects at baseline

Whole SBI Whole PI

SBI control 0.93 –PI control – 0.89

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272 Rosin et al.

Silness & Löe plaque index (PI) (Sil-ness & Löe 1964), the sulcus bleedingindex (SBI) (Mühlemann & Son 1971),and the measurement of gingival crevic-ular fluid (GCF) on teeth 16, 12, 24, 36,32, and 44 (Fig. 1). The Mühlemannand Son sulcus bleeding index is verysimilar to the gingival index accordingto the criteria of Löe & Silness (1963),but records bleeding on probing as anearly symptom of inflammation at anotherwise healthy gingival site. At the1-, 4-, 8-, and 10-week examinations,the GI, PI, and amount of GCF wasassessed on teeth 16, 12, 24, 36, 32, and44. The correlation between the full-mouth SBI and PI and the SBI and PIof the selected control teeth at the base-line examination is given in Table 2.

Test dentifrices

The toothpastes consisted of a gel basis(3.25 % hydroxyethylcellulose) with nodetergents or abrasives, only with addi-tives to correct flavor (0.40 % saccharin,0.85 % menthol, 0.31 % peppermint oil)and 0.15% methylparaben. SCNª wasadded as a combination of the sodiumand potassium salt. H2O2 was added ascarbamide perhydrate. The gel basiswith no active ingredients served as theplacebo (Table 1) and was also used bythe test groups in the last two weeks(wash-out) of the trial. Each subject re-ceived 2 plain white tubes – labeled witha number and coded A and B – whichcontained the gel with an active ingredi-

Table 3. PI – median (interquartile range) in the study groups

Group Baseline 1 week 4 weeks 8 weeks π2 weeks placebo

group A(placebo)(nΩ36–40) 0.33 (0.36) 0.28 (0.41) 0.33 (0.30) 0.33 (0.22) 0.33 (0.34)group B(0.1 SCN)(nΩ17–20) 0.39 (0.37) 0.39 (0.36) 0.28 (0.34) 0.42 (0.39) 0.42 (0.32)group C(0.5 SCN)(nΩ16–20) 0.33 (0.41) 0.33 (0.36) 0.31 (0.31) 0.36 (0.34) 0.25 (0.61).group D(0.1 SCN/0.1 H202)(nΩ15–20) 0.31 (0.27) 0.17 (0.33) 0.28 (0.27) 0.33 (0.32) 0.33 (0.28)

..

group E(0.5 SCN/0.1 H202) 1) a 1) b 1) c 2) a(nΩ16–20) 0.36 (0.41) 0.31 (0.17) 0.22 (0.36) 0.22 (0.20) 0.42 (0.47)group F(0.1 H202) 1) d 2) b(nΩ18–20) 0.44 (0.36) 0.31 (0.37) 0.33 (0.35) 0.17 (0.28) 0.39 (0.27)

1) Statistically significant different from baseline (a pΩ0.009, b pΩ0.017, c pΩ0.005, d pΩ0.003).2) Statistically significant different from π 2 weeks placebo (a pΩ0.001, b pΩ0.005).] Statistically significant difference between treatment groups and placebo group (. pΩ0.017, .. pΩ0.032).

ent or the gel basis only (Table 1). Thesubjects were instructed to apply equalamounts (1.5 cm) of gel from each tubeonto the toothbrush so that mixingtook place during toothbrushing.

Clinical examination

The 140 subjects were examined by 3 in-vestigators (47, 47, 46), but all 5 exami-nations of a given patient were carriedout by the same investigator. Prior to thestudy, calibration sessions according toNordstrom et al. (1988) were carried outto standardize responses. Inter-examinerreliability was determined through clin-ical examinations of patients in which a4th clinician was used to manipulate thetissue while the 3 investigators indepen-dently scored gingival inflammation andplaque accumulation. 8 sessions, exam-ining 3 patients each time, were per-formed during 5 weeks prior to the be-ginning of the study.

At the beginning of the clinical ex-amination, plaque was quantified at 3sites (buccal, mesiobuccal, lingual). Be-fore GCF flow measurements, the testteeth were first isolated with cottonwool rolls. After plaque and saliva werecarefully cleared from the buccal sur-faces, the teeth were dried with a gentlestream of air. 2¿8 mm paper strips(Whatman 3 MM chromatographypaper, Whatman Lab Sales Ltd., Maid-stone, UK) were inserted with theirrounded tips into the mesiobuccal crev-ice of the test teeth until mild resistance

was felt and left in place for 90 s. Theamount of fluid collected was deter-mined with the Periotron 6000 (HarcoElectronics Ltd., Winnipeg, Canada).

The SBI was assessed at 6 sites (dis-tobuccal, buccal, mesiobuccal, distolin-gual, lingual, mesiolingual) of the se-lected teeth using using CP-15UNCprobes (HU-Friedy Europe, Leimen,Germany).

Statistical analysis

Inter-examiner reliability was deter-mined by calculating k coefficients. Thebaseline values were compared to thevalues at the 1-, 4-, and 8-week exami-nation with the Wilcoxon signed-rankstest. Using the same test, the wash-outvalues were compared to the values atthe 8-week examination. The Mann-Whitney U-test was used to test forpossible differences between the treat-ment groups and the placebo group. Noexplicit adjustment was made formultiple comparisons and the p-valueshave to be interpreted with caution.

ResultsInter-examiner reliability/compliance

In the last calibration session, an inter-examiner reliability of k>0.79 andk>0.83 was achieved for the SBI and PI,respectively. Of the 140 subjects whostarted the trial, 128 completed the en-tire 10-week period. Some patients com-

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SCNª/H2O2 combinations 273

Table 4. SBI – median (interquartile range) in the study groups

Group Baseline 1 week 4 weeks 8 weeks π2 weeks placebo

group A(placebo)(nΩ36–40) 1.06 (0.50) 1.03 (0.48) 1.04 (0.52) 1.03 (0.79) 0.99 (0.69)group B(0.1 SCN) 1) a 1) b(nΩ17–20) 1.17 (0.86) 1.03 (0.53) 0.94 (1.07) 1.12 (1.07) 1.28 (0.98)group C(0.5 SCN) 1) c(nΩ16–20) 1.03 (0.49) 1.06 (0.54) 0.87 (0.56) 1.03 (0.57) 1.10 (0.63)..group D(0.1 SCN/0.1 H202) 1) d(nΩ15–20) 0.92 (0.55) 0.89 (0.64) 0.86 (0.36) 0.89 (0.47) 0.92 (0.39)

.

group E(0.5 SCN/0.1 H202) 1) e 1) f 1) g 2) a(nΩ16–20) 1.01 (0.44) 0.90 (0.65) 0.97 (0.59) 0.76 (0.59) 1.03 (0.45)group F(0.1 H202)(nΩ18–20) 1.22 (0.77) 1.24 (0.50) 1.17 (0.56) 1.00 (0.53) 1.00 (0.62)

1) Statistically significant different from baseline (a pΩ0.018, b pΩ0.029, c pΩ0.014, d pΩ0.046, e pΩ0.010, f pΩ0.006, g pΩ0.000).2) Statistically significant different from π2 weeks placebo (a pΩ0.002).] Statistically significant difference between treatment groups and placebo group (. pΩ0.023, .. pΩ0.047).

Table 5. GCF (Periotron 6000) – median (interquartile range) in the study groups

Group Baseline 1 week 4 weeks 8 weeks π2 weeks placebo

group A(placebo) 1)* 1)*(nΩ39–40) 18.3 (22.7) 19.2 (13.2) 15.6 (20.0) 16.7 (12.3) 16.0 (16.4)group B(0.1 SCN)(nΩ19–20) 23.7 (17.0) 20.8 (16.5) 18.7 (16.7) 20.0 (21.0) 19.0 (14.2).

..group C(0.5 SCN) 1)**(nΩ19–20) 20.3 (26.9) 22.9 (17.8) 20.0 (16.4) 21.1 (15.2) 25.4 (21.2)group D(0.1 SCN/0.1 H202)(nΩ20) 19.8 (22.1) 19.4 (14.8) 12.7 (17.3) 20.8 (24.9) 17.8 (21.1)group E(0.5 SCN/0.1 H202) 1)***(nΩ20) 18.8 (24.6) 12.4 (18.0) 14.0 (17.4) 10.7 (9.4) 14.6 (9.9)

...

group F(0.1 H202) 1)****, 2)*(nΩ19–20) 19.6 (18.1) 18.3 (13.2) 17.8 (18.2) 12.0 (6.8) 17.3 (17.0)

1) Statistically significant different from baseline (* pΩ0.005, ** pΩ0.019, *** pΩ0.025, **** pΩ0.006).2) Statistically significant different from π2 weeks placebo (* pΩ0.001).] Statistically significant difference between treatment groups and placebo group (. pΩ0.02, .. pΩ0.036, ... pΩ0.033).

plained about the fact that no foam wasgenerated during toothbrushing; other-wise, no adverse reaction was reported.

Dental plaque

When the plaque scores in the treat-ment groups were compared to theplaque scores in the placebo group,statistically significant differences werefound for groups E and F at the 8-weekexamination (Table 3). In the placebogroup (group A) and the test groups B,C, and D there was no change in PI be-

tween baseline and the subsequent ex-aminations. However, the PI was sig-nificantly lower compared to baseline at1, 4, and 8 weeks in group E and at 8weeks in group F (Table 3). In groupsE and F, there was also an increase inthe PI after the wash-out period (π2weeks placebo) as compared to the 8-week examination (Table 3).

Sulcus bleeding index

At 8 weeks, group E exhibited a sig-nificantly lower SBI than the placebo

group, whereas in group F, the SBI atthe 1-week examination was signifi-cantly greater compared to baseline(Table 4). In group E, gingival healthwas better at 1, 4, and 8 weeks whencompared to baseline, and worsenedthereafter when the placebo was usedfor the last 2 weeks of the trial (Table4). Significant differences from baselinewere also observed in group B at 1 and8 weeks, in group C at 4 weeks, and ingroup D at 1 week (Table 4). There wereno changes in the SBI in the placebogroup and in group F.

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274 Rosin et al.

Gingival crevicular fluid

The comparison between the treatmentgroups and the placebo group revealedthat at the 8-week examination, theamount of GCF was higher in groupsC and D and lower in group F as com-pared to the placebo group (Table 5).The decrease in the amount of GCF ascompared to baseline was statisticallysignificant for group A at 4 and 8weeks, for group C at 4 weeks, and forgroups E and F at 8 weeks (Table 5). Ingroup F, there was also an increase inthe amount of GCF after the wash-outperiod (π2 weeks placebo) as comparedto the 8-week examination (Table 5).

Discussion

Participation in a clinical trial is com-monly associated with an improvementin the oral hygiene and the oral healthstatus regardless of the test agent used.This phenomenon is related to the pla-cebo effect (for review, see Glavind &Nyvad (1987)). Prior to the beginning ofthe present study, all participants used acommercial toothpaste. At baseline, thecommercial toothpaste was exchangedfor a test toothpaste which was a hydro-xyethylcellulose gel without abrasives ordetergents. Although not assessed, theworse cleansing properties of the test gelcould be expected to result in worseningof the oral hygiene status among the par-ticipants. However, this was probablycompensated by the placebo effect,which led to the observation that nochanges whatsoever occurred in the PIand SBI in some groups.

Groups E (0.5% SCNª, 0.1% H2O2)and F (0.1% H2O2) exhibited a statisti-cally significant reduction in plaquescores from baseline and an increase inplaque scores when the active formulawas exchanged for the placebo in the last2 weeks of the trial (Table 3). This canpartially be explained by the direct anti-bacterial effect of H2O2 and by the in-direct antibacterial effect of H2O2 in theperoxidase system (Tenovuo & Pruitt1984). However, the antiplaque effectwas somewhat more pronounced ingroup E, which also had a significantlylower PI than the placebo group at the 8-week examination. This may be an indi-cation of additive or synergistic effectsdue to high concentrations of thio-cyanate (0.5%). Thiocyanate is not onlya cofactor in the peroxidase system(Tenovuo & Pruitt 1984), it also en-hances the antibacterial effect of lyso-

zyme (Pollock et al. 1981, 1983, Wilkenset al. 1982). Lumikari & Tenovuo(1991b) found that physiological con-centrations of thiocyanate were not highenough to trigger lysozyme-mediatedcell lysis in human saliva. However, in aseries of studies, it was demonstratedthat at concentrations of 30 mM andhigher, thiocyanate can trigger cell lysiswhen added to lysozyme-treated strepto-cocci at neutral pH (Pollock et al. 1981,1983).

All groups with SCNª (groups B, C,D and E) showed – at least at some pointduring the study – an improvement inSBI scores compared to baseline (Table4). Again, the effects were most pro-nounced in group E, which exhibited asignificant reduction of gingival in-flammation after an 8-week period ascompared to the placebo group. In theplacebo group (A) and in group F (0.1%H2O2), no changes in the SBI could beobserved. These findings seem to sup-port the concept of synergistic effects ofthe two active components. In this study,carbamide perhydrate was used as a hy-drogen peroxide donor for the first time.Carbamide perhydrate not only pro-motes the availability of H2O2, but theurea which is generated also facilitatesSCNª penetration into the oral mucosa(Wohlrab 1989) and thus supports the ef-ficacy of SCNª in the periodontal tissue.SCNª enhances proliferation and re-generation (for review, see Kramer &Böhland (1996)), the effect being par-ticularly pronounced in rapidly prolif-erating tissues, e.g., in wound healing.The positive effect of a combined use ofthe 0.5% SCNª 0.1% H2O2 (group E) isalso reflected in the GCF data. Using thetoothpaste E for 8 weeks led to a signifi-cant reduction in the amount of GCFcompared to baseline (Table 5).

To conclude, this study verifies that atoothpaste containing a combination of0.5% SCNª and 0.1% H2O2, using car-bamide perhydrate as a H2O2 donor, iseffective in reducing plaque and gingivalinflammation.

Acknowledgements

The authors would like to thank GebroBroschek GmbH (Fieberbrunn/ Aus-tria) for producing and providing thetest dentifrices.

Zusammenfassung

Auswirkung von Thiozyanat-H2O2-Kombina-tionen in Zahnpasten auf Plaque und Gingivitis

Zielsetzung: Eine 10 Wochen dauernde place-bokontrollierte Doppelblindstudie wurde bei140 mannlichen Probanden durchgefuhrt,um die Auswirkungen von 5 Zahnpasten, dieverschiedene Kombinationen von Thiozy-anat (SCNª) und Wasserstoffperoxide(H2O2) enthielten, auf Plaque und Gingivitiszu untersuchen.Material und Methoden: Die Zahnpasten be-standen aus einer Gelbasis ohne jegliche De-tergentien oder Putzkorper (Placebo, GruppeA), der SCNª und/oder H2O2 wie folgt bei-gemengt waren: 0.1% SCNª (Gruppe B),0.5% SCNª (Gruppe C), 0.1% SCNª/0.1%H2O2 (Gruppe D), 0.5% SCNª/0.1% H2O2

(Gruppe E) und 0.1% H2O2 (Gruppe F). ZuBeginn der Studie wurden der Plaque Index(PI), der Sulkus-Blutungs-Index (SBI) unddie Sulkusflussigkeitsfließrate (SFFR) mitdem Periotron 6000 an den Zahnen 16, 12,24, 36, 32 und 44 bestimmt. Die Probandenwurden zufallig der Placebogruppe (nΩ40)oder einer der 5 Testgruppen (nΩ20) zuge-wiesen und benutzten die entsprechendeZahnpasta uber einen Zeitraum von 8 Wo-chen. Schließlich benutzte jeder Proband diePlacebopasta fur weitere 2 Wochen (‘‘wash-out’’). Nachuntersuchungen fanden nach 1, 4und 8 Wochen sowie nach der ‘‘wash-out’’-Periode statt.Ergebnisse: Zur 8-Wochen-Nachuntersu-chung war der PI in den Gruppen E (pΩ0.017) und F (pΩ0.032) niedriger als in derPlacebogruppe. Der SBI in Gruppe F war imVergleich zur Placebogruppe nach einer Wo-che erhoht (pΩ0.023) und in Gruppe E nach8 Wochen reduziert (pΩ0.047).Schlußfolgerungen: Die Ergebnisse zeigen,daß eine Zahnpasta, die 0.5% SCNª und0.1% H2O2 aber keinerlei Detergentien oderPutzkorper enthalt Plaque hemmen und Gin-givitis reduzieren kann.

Resume

Effets de combinaisons SCNª/H2O2 dans lesdentifrices sur la plaque et la gingiviteUne etude clinique en double aveugle,controlee par un placebo, sur 10 semaines aete realisee sur 140 sujets masculins pour de-terminer les effets sur la plaque et la gingivitede 5 dentifrices contenant des combinaisonsvariees de thiocyanate (SCNª)/peroxyded’hydrogene (H2O2). Les dentifrices etaientconstitues d’une base de gel sans detergentsni abrasifs (placebo, groupe A) a laquelleetaient ajoutes SCNª et/ou H2O2 commesuit: 0.1% SCNª (groupe B), 0.5% SCNª

(groupe C), 0.1% SCNª/0.1% H2O2 (groupeD), 0.5% SCNª/1% H2O2 (groupe E), et0.1% H2O2 (groupe F). Un examen initialetait realise au cours duquel, l’indice de pla-que de Silness et Loe (PI), l’indice de saigne-ment sulculaire de Muhlemann et Son (SBI),et la quantite de fluide gingival (GCF)etaient enregistres en utilisant le Periotron6000 sur les dents 16, 12, 24, 36, 32 et 44. Lessujets etaient assignes au hasard soit dans legroupe placebo (nΩ20), soit dans un groupetest (nΩ20) et utilisaient leur dentifrices

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SCNª/H2O2 combinations 275

respectifs pendant une periode de 8 semaines.Finalement, chaque groupe utilisait le place-bo pendant 2 semaines supplementaires (les-sivage). Une reexamination etait realisee ap-res 1, 4, 8 semaines et apres la periode delessivage final de 2 semaines avec les menesindices qu’a l’examen initial. Les modifica-tions intragroupe etaient analysees par le testde Wilcoxon signed ranks, en utilisant les in-dices initiaux et ceux releves lors de la perio-de de lessivage. Le test de Mann-Whitney Ufut utilise pour comparer les groupes test etle groupe placebo. A l’examen de la huitiemesemaine, les indices de plaque du groupe E(pΩ0.017) et du groupe F (pΩ0.032) etaientplus bas que dans le groupe placebo. L’indicede saignement sulculaire du groupe F apresune semaine etait augmente (pΩ0.023) et leSBI du groupe E apres 8 semaines etait dimi-nue (pΩ0.047), compare au groupe placebo.Les resultats montrent qu’un dentifricecontenant 0.5% SCNª et 0.1% H2O2, maisni detergents, ni abrasifs, inhibe la plaque etreduit la gingivite.

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Address:

Michael RosinDepartment of Operative Dentistry, Periodon-tology and Pediatric DentistrySchool of Dentistry, University of GreifswaldRotgerberstr. 8D 17489 GreifswaldGermany

fax: π49 3834 867171e-mail: rosin/uni.greifswald.de