Caries Res. 12 (Suppl. 1): 74-82 (1978)

Anti-Plaque Therapeutics in Caries Prevention1 Goran Frostell and Yngve Ericsson Department of Cariology, Karolinska Institute, Stockholm

1 Due to misunderstanding and delay, the authors originally assigned the task of writing this chapter did not succeed in presenting their manuscript in time. For this reason, and in order not to leave an obvious gap in the logical arrangement of the chapters, Prof. Goran Frostell produced this text in collaboration with the editor as a last-minute review of the anti-plaque therapeutic approach to caries prevention. Hence, practically only the main features, a few examples, and references to reviews could be included.

originating from saliva and adsorbed onto hydroxyapatite. Microorganisms colonize the pellicle by complicated adsorption mechanisms involving negatively and posi­ tively charged groups in the pellicle as well as on the surfaces of the microorganisms. Bacterial production of extracellular poly­ saccharides, mainly dextrans and levans, is involved in this process and contributes to increased plaque adherence and plaque volume. The capacity of forming extracellu­ lar polysaccharides and abundant plaque is considered to be one of the main causes of the cariogenicity of Streptococcus mutans and Streptococcus sanguis [reviews: Klein­ berg, 1974; Bowen, 1976; Theilade and Theilade, 1976; Fitzgerald, 1976; Hardie and Bowden, 1976; Costerton et al., 1978], Many other details in our knowledge of oral microbiology, salivary properties and tooth surface phenomena form points of departure for caries-preventive approaches [Poole and Newman, 1971; Gibbons and van Houle, 1973].

Antiseptics

The number of microorganisms per unit volume of saliva has often been determined in bacteriological tests. The figure thus ob­

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For many years, numerous efforts have been made to reduce dental plaque forma­ tion, dental caries and periodontal disease by the application of therapeutic remedies and various drugs. As early as 1890, Miller observed that ‘we may counteract or limit the ravages of (caries) ...(4) by the proper and intelligent use of antiseptics to destroy the bacteria, or at least to limit their number and activtiy’. There is now' a vast literature on caries-preventive or plaque-reducing studies using antiseptics, anti-enzymatic drugs, antibiotics, enzymes, vaccines and methods aiming at changing the ecology of the oral cavity. The knowledge of the mechanisms in­ volved in dental plaque formation has been greatly improved in recent years. The for­ mation of an enamel pellicle is the earliest evidence of plaque development. This layer consists of acidic proteins and glycoproteins

tained has been believed to mirror the num­ ber of microorganisms in the dental plaques and in the crevices of the tongue and the bacterial accumulations on other soft tissues in the oral cavity. It has been found that this bacterial count changes in a characteristic way during the day, being highest in the morning. It is reduced to about 50% after the first meal, then rapidly increases and is again reduced at each meal. During the night, the bacterial count rises slowly reaching its individually characteristic top level in the morning (Ap­ pleton, 1950], The steep increase in the number of bacteria between meals also indi­ cates the speed with which the oral flora is restituted after a reduction caused by anti­ bacterial influences. Early investigations revealed that by the influence of rinsing or brushing with anti­ septic solutions the bacterial count could be reduced by about 50%. The original charac­ teristic number was reached again in about 0.5-1.4h. This phenomenon reflects the short regeneration time, about 20 min, of many of the oral microorganisms, especially the streptococci [reviews: Keyes and Shern, 1971; Parsons, 1974; Loesche, 1975]. Thus, it was concluded that in order to influence plaque formation or periodontal disease an antibacterial drug would have to be administered at very short intervals over the whole day and night, which is not pract­ ical. A partial explanation of the very tran­ sient effect of antiseptics administered as rinses or brushing was obtained by the stud­ ies of Swenander-Lanke [1957]. These find­ ings explain that it has seldom been possible to influence plaque formation, dental caries or periodontal disease with antiseptics ad­ ministered several times a day as mouth rin­ ses or as ingredients in toothpastes. Howev­

75

er, caries prevention might theroetically be effected by plaque reduction or inhibition before or during the ingestion of carbohy­ drate substrate. In the 1940s, quaternary ammonium compounds were introduced. These antisep­ tics combine great efficiency against gram­ positive organisms with surface-active prop­ erties. Animal studies as well as human studies revealed that by frequent use of these substances dental plaque formation could be reduced. Slight influences on den­ tal caries and periodontal disease were also reported by certain authors [Review: Par­ sons, 1974]. In 1962, Strdlfors showed that on rinsing with highly effective antiseptics such as chloramine, the plaque flora was only re­ duced to about 10-30% of its orginal amount. However, if the drug was adminis­ tered as a gel in a tray and applied to the teeth for 5-10 min it was possible to reduce the number of microorganisms to 0.1 or 0.01%. In the first instance, with only a par­ tial reduction of the number of microorga­ nisms, the original number was quickly re­ stored again, whereas if a reduction to less than 0.1% was achieved, it took 6-8 h until the original characteristic number of mi­ croorganisms was restored. Oxidizing agents have been widely used as oral antiseptics and anti-plaque remedies, for example hydrogen peroxide and sodium perborate. Ericsson and Lundbeck [1955] tested the red-ox reaction of ascorbic acid with peroxide using copper ions as catalyst. This splits polymers of the bacterial cell walls as well as the mucoid of the saliva and re­ duces plaque accumulation [Johansen et al., 1970]. However, constant use several times a day for long periods of time is probably contraindicated.

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Anti-Plaque Therapeutics in Caries Prevention

Encouraging results were obtained when chlorhexidines appeared on the market. These antiseptics are highly effective against the oral flora and adhere to tooth surfaces and dental plaque, and rinsing with these substances reduces the number of microor­ ganisms in the saliva and plaques so effec­ tively that dental plaque formation, dental caries and periodontal disease are inhibited. This has been demonstrated in a number of clinical studies carried out primarily by Danish and Norwegian scientists. There has been a wave of enthusiasm in this field [re­ views: Parsons, 1974; Loesche, 1975]. However, most authors feel that such a use of highly effective antibacterial substances is contraindicated for the following reasons: (1) drug resistance may develop in the mi­ croorganisms; (2) on repeated use of the an­ tibacterial agents, toxic or allergic reactions may occur in the soft tissues, and (3) taste sensations may be affected. In the case of chlorhexidine there have been several reports of adverse side-effects; e.g. taste sensations are strongly affected by this as well as by many other antiseptics when applied in intraorally effective con­ centrations. Fluorides have been used in combination with antiseptics, for example chlorhexidine, and this combination appears to be more effective in the reduction of experimental dental caries than cither component alone [Sherp, 1971].

Enzyme Inhibitors Many scientists have tried to find meth­ ods to prevent dental plaque formation, dental caries and periodontal disease by blocking microbiological enzyme reactions.

Early examples of this are the uses of anti­ septics, metal ions such as copper and zinc, vitamin K, amino acids, polyphenols such as flavoncs and flavanones, monoiodoacetic acid, protamine and fluoride [reviews: Mad­ sen, 1970; Keyes and Shern, 1971; Parsons, 1974], It was obvious that these methods were bound to fail if the substances could not be administered many times a day or if they could not be applied in a way that se­ cured their adherence to the teeth for a long period of time. Several of the substances mentioned have been shown to have the ex­ pected properties in vitro and in some in­ stances also in vivo, but they have been either too toxic or too ineffective to be used clini­ cally. From a large number of inhibition tests with different enzyme inhibitors two sub­ stances emerged - sodium lauroyl sarcosinate and sodium dehydroacetate. These enzyme inhibitors accumulated in and adhered to dental plaque material and were shown to exert an influence on acid production for many hours. Toothpastes containing either of these substances are still on the market but scientific evidence of their effect against dental caries is conflicting [Manly, 1954]. Fluoride is to be mentioned separately. Some of the many mechanisms of anticaries action of fluoride are believed to be the in­ hibition of either bacterial growth, polysac­ charide formation or acid production [Ham­ ilton, 1977; Kleinberg et al., 1977; Rolla, 1977]. It has been shown that inhibition of acid production, which is due to the influ­ ence of several plaque enzymes but espe­ cially enolase, requires high concentrations of F~ ions. The lowest concentration effect­ ing a partial inhibition of the acid produc­ tion is about 10-20 ppm whereas even 500 ppm does not always inhibit acid for­

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76

Anti-Plaque Therapeutics in Caries Prevention

Antibiotics

A number of antibiotics have been shown in experimental animal studies to re­ duce dental plaque formation and dental caries. Such properties have been ascribed to penicillin, aureomycin, terramycin, strep­ tomycin, bacitracin, subtilin, Chloromycetin, concanavallin A, and polymyxin, among others [reviews: Parsons, 1974; Loesche, 1975]. It has been shown that antibiotics active against gram-positive microorganisms are the most effective in reducing plaque formation and dental caries in experimental animals. Children on long-term medication with penicillin for treatment of rheumatic diseas­ es and prevention of heart failure have low­ er caries incidence than healthy children of their own age. Frostell [1972] showed that on medication with penicillin the number of microorganisms in the dental plaque was significantly reduced and the pH decrease in the dental plaque material after a 10%> sugar rinse was also significantly reduced. Thus, beyond doubt, antibiotics effective against gram-positive microorganisms may reduce dental plaque formation, dental car­ ies and even periodontal disease if used re­ peatedly for long periods of time. However, such a use of these potent remedies is con­ sidered to be contraindicated by most scien­ tists for a number of reasons. Drug-resistant microorganisms may appear and toxic or al­ lergic reactions may occur in some individu­ als. Most scientists seem to be of the opinion that antibiotic drugs should not be used constantly for prevention of plaque forma­ tion, dental caries and periodontal disease. However, they may be used for short-period medication on very specific indications, for example in subjects with rampant dental

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mation in saliva completely. Polysaccharide production as well as the growth of some microorganisms may be reduced by concen­ trations of fluoride existing in dental plaque. It is well known that in areas with a cer­ tain fluoride content in the drinking water dental caries is strongly reduced. One of the mechanisms of fluoride has been thought to be a reduction of dental plaque formation. This is possible because the surface of the tooth and surfaces of dental restorative ma­ terials contain a number of free charges making possible an accumulation of materi­ al at the surface. Fluorides are very effec­ tive reducers of this free surface energy. Thus, one mechanism of fluoride may be a reduction of free surface energy and of den­ tal plaque formation [Ericson and Ericsson, 1967\Glantz, 1969; Rolla and Melsen, 1975]. Dental plaque fluoride concentration is high and clearly correlated with the fluoride concentration in drinking water. The accu­ mulation of fluoride in dental plaque may be great enough to exert some inhibition of polysaccharide and acid production, partic­ ularly in the lowest intraoral pH range where F" ions are liberated from their inor­ ganic or organic binding. However, the low­ est fluoride concentrations in plaque may even stimulate enzymatic action. It has fur­ ther been shown that plaque bacteria may acquire greatly increased resistance to fluo­ ride, possibly by reduced membrane perme­ ability to the fluoride ions. On the whole, although the presence of fluoride at the enamel surface is an impor­ tant cariostatic factor, and although fluoride is concentrated in the dental plaque, we still do not know whether fluoride interference with the caries-inducing metabolism of the plaque is one of the more important cario­ static mechanisms of fluoride.

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Enzymes

Numerous experiments have been car­ ried out in order to find methods to remove dental plaque and to reduce dental caries and periodontal disease by the use of differ­ ent enzymes. Hydrolytic enzymes have been used which split the glycoproteins of the sa­ liva and the plaque, and proteolytic enzymes active against proteins in the oral environ­ ment as well as enzymes active against the polysaccharides of the dental plaque. Hydrolytic enzymes such as pronase, neuraminidases and other bacterial hydro­ lases have not been extensively tested. They have an excellent effect on salivary glyco­ proteins but do not seem to be equally effec­ tive in dissolving dental plaque. Proteolytic enzymes such as trypsin and pepsin are not very effective in reducing the viscosity of saliva or dissolving dental plaque and when used in high concentrations they may injure the soft tissues of the oral cavity. Protein-dissolving enzymes and glycoly­ tic enzymes have been used separately and in combination in mouth rinses and in toothpastes but have not reached scientific approval for clinical use although some preparations like mutanolysin have given encouraging results [Yokogawa, 1974; Osugi et al., 1974; Inoue et al., 1974]. However, in this field much remains to be done. From early studies with lactoperoxidase preparations favorable results were re­

ported, which, however, have not been con­ firmed so far [Hugosson et al., 1974], Bacterial production of extracellular po­ lysaccharides such as a-1-6 dextrans or a-1-6 and a-1-3 polyglucans or mutans are considered to be of great importance in den­ tal plaque formation. A number of polysac­ charide-splitting enzymes from different sources with action on both a-1-6 linkages and a-1-3 linkages have been used separate­ ly and in combination. The results reveal that when these enzymes are administered in the diet simultaneously with dental plaque formation they may exert plaque in­ hibition and a reduction of dental caries whereas if they are given after dental plaque formation has taken place, they do not re­ move the plaque. Their anticarious action is very slight, if any. However, the effect of different enzymes and enzyme combinations against dental plaque seems to have been inadequately studied so far and this may be a promising field for further investigations [Guggenheim, 1970; Lobene, 1971; Gug­ genheim et al., 1972; Kelstrup et al., 1973; Murayama, 1973].

Immunization

Search for vaccines active against oral microorganisms and against dental caries is a field of great interest at present. From a theoretical point of view, however, it would seem futile to try to use the most specific of all scientific methods, the antigen-antibody reaction, against dental plaque formation, dental decay and periodontal disease which are generally accepted as phenomena caused by a mixed flora of many different species of microorganisms. Furthermore, if the antibodies are expected to act in the oral

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caries when it is desirable to change the flo­ ra rapidly, or in persons with Vincent’s sto­ matitis, or after periodontal surgery to pre­ vent plaque formation and postoperative complications [Handelman et al., 1962; Loesche et al., 1971; Lobene et al., 1972],

cavity they should be expected to be mediat­ ed by the saliva in which antibody concen­ tration is generally low [reviews: Sims, 1970, 1972; Taubman, 1973]. S. mutans has been considered by many researchers to be the main cause of dental caries, and consequently many efforts of lat­ er years have been directed against this mi­ croorganism. Vaccines against S. mutans cells have been found active in reducing dental decay in rats and monkeys infected with this organism. However, caries in hu­ mans does not seem to parallel antibody ti­ ters against S. mutans. It seems more rational to try to develop antibodies against specific enzymes which are considered to be of fundamental import­ ance in the development of dental plaque, dental caries and periodontal disease. Socalled caries-inducing or cariogenic strepto­ cocci are considered to distinguish them­ selves among other organisms in the caries process by their capacity to produce en­ zymes, dextran sucrases or levan sucrases, which favor the formation of polysaccharide products on the tooth surface. Thus, it seems logical to try to develop vaccines against such enzymes, which could proba­ bly be similar for a number of microorgan­ isms involved in dental plaque formation. However, immunization with glucosyltransferases in monkeys have failed to pro­ vide protection against caries [Bowen et al., 1975], Vaccines against dextrans and mutans have been developed since these substances are believed to play an important role for the adherence of microorganisms to tooth surfaces, but so far these vaccines have shown no effect against dental plaque for­ mation and dental caries. However, due to the very complex nature of dental plaque

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formation, dextran and mutan production and the enzymology of this field, there is still some hope that vaccines may be devel­ oped, which are effective against dental plaque formation, dental caries and/or per­ iodontal disease. The saliva contains agglutinins which adhere to the oral microorganisms and cause an agglutination of the organisms, thus pre­ venting them from accumulating on the tooth surfaces [Magnusson et al., 1976]. Theoretically, a way of vaccination against dental caries would be to increase the forma­ tion of such agglutinins in the saliva. It is known that the production of salivary agglu­ tinins is hormonally controlled, e.g. by menstruation and hormonal contraceptives. However, recent results indicate that these agglutinins are not immunoglobulins [Ericson and Magnusson, 1976; Kashket and Guilmelte, 1978], Nevertheless, immunization against den­ tal plaque formation, dental caries and periodontal disease has many aspects and much still remains to be done in this field [Guggenheim et al., 1969; Guggenheim, 1970; Williams and Gibbons, 1972; Taub­ man, 1973; Bowen et al., 1975].

Changes in the Ecology o f the Oral Cavity

Many authors have described dental plaque formation, dental caries and peri­ odontal disease as results of changes in the ecology of the oral cavity. It has been ade­ quately demonstrated in a great number of studies that this ecology may be changed by variation of the diet. Increased and frequent administration of fermentable sugar will cause an increase in the total number of mi­ croorganisms in the oral cavity as well as an

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Anti-Plaque Therapeutics in Caries Prevention

Frostell/Ericsson

80

shown in some studies. In uremia, dental calculus formation may be very much in­ creased. Implantation of new species of microor­ ganisms is another mode of experimenta­ tion in order to change the ecology of the oral cavity. A number of studies have been carried out in order to evolve a change in the oral flora. New such strains are, howev­ er, rapidly eliminated from the oral cavity, and experiments seem to confirm the belief that in order to establish a new strain in the oral environment it is also important to change factors such as the diet or the sali­ vary composition. Such changes are rather difficult to establish. However, lately the in­ troduction of non-pathogenic mutants of S. mutans opened a new approach to this problem [de Stoppelaar et al., 1971].

Conclusions

Anti-plaque and antimicrobial measures have so far had little clinical effect in reduc­ ing caries, with the possible exception of fluorides; it is not known, however, whether fluoride effects on plaque microbes and their metabolism account to any major de­ gree for the powerful, multifaceted cariostatic action of fluorides. Other types of measures have all had ei­ ther weak effects or serious side-effects, or both: antiseptics: effects generally weak or of too short duration; practically always con­ comitant damage to oral mucosa and taste cells; antibiotics: more effective than antisep­ tics, but also serious side-effects; antienzymatics: weak and inconsistent effects;

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increase in the number of streptococci, lactobacilli and Candida yeasts. It is a common goal in the treatment of dental caries to es­ tablish certain food habits in order to change the ecology back to a more ‘natural’ state of order. Even minor changes in the diet may cause extensive changes in the oral ecology. For example, it has been shown that dogs given throat and lung tissues as their sole diet are healthy and have very small amounts of dental plaque, whereas if they re­ ceive the same type of food minced or pul­ verized they develop dental plaque and gin­ givitis in a few weeks. The flora also changes qualitatively, with an increased proportion of proteolytic microorganisms in the plaque. Early investigations indicated a change in the oral ecology by administration of am­ monium ion or urea. These substances seem to reduce the number of lactobacilli and streptococci in the dental plaque and saliva, and ammoniated dentifrices were developed in the wake of these results and still hold some of the market. Several studies indicat­ ed an effect on dental caries by such denti­ frices whereas careful studies carried out at a later date did not confirm the results. More­ over, it is known that S. mutans and S. san­ guis may utilize ammonium ion for speciesspecific protein formation, and it has been noticed in experimental studies in animals that addition of urea (which increases the concentration of ammonium ion in the oral cavity) increases dental plaque formation and periodontal disease. Thus, most authors now consider it contraindicated to use denti­ frices containing ammonia or urea. The al­ kaline pH of the dental plaque, which is a consequence of the urea administration, will also increase formation of dental calculi as

vaccinations: little promise even in theo­ ry; no established effect in humans. However, there still appear to be enough theoretical prospect to encourage continued basic research in this field, e.g. concerning factors interfering with bacterial adherence to tooth surfaces; factors favoring a non-acidogenic plaque flora; specific applications or specific retention of effective drugs on the tooth surface. References Appleton, J. L. T.: Bacterial infection with special reference to dental practice (Lea & Febiger, Philadelphia 1950). Bowen, W. H.: Nature of plaque. Oral Sciences Rev. 9: 3-21 (1976). Bowen, W. H.; Cohen, G., and Colman, G.: Im­ munisation against dental caries. Br. dent. J. 139: 45-58 (1975). Costerton, J. W.; Geesey, G. G. and Cheng, K.-J.: How bacteria stick. Scient. American 238: 86-95 (1978). Ericson, T. and Ericsson, Y.: Effect of partial fluorine substitution on the phosphate ex­ change and protein adsorption of hydroxylapatite. Helv. odont. Acta 11: 10-14 (1967). Ericson, T. and Magnusson, I.: Affinity for hydro­ xyapatite of salivary substances inducing agglu­ tination of oral streptococci, Caries. Res. 10: 8-18 (1976). Ericsson, Y. and Lundbeck, H.: Antimicrobial effect in vitro of the ascorbic acid oxidation. Acta Path. Microbiol. Scand. 37: 493-527 (1955). Fitzgerald, R. J.: The microbial ecology of plaque in relation to dental caries; in: Stiles, Loesche and O'Brien, Microbial aspects of dental car­ ies. Microbiol. Abstr. 3: 849-858 (1976). Frostell, G.: Sackaroshaltig penicillinmixtur och kariesprocessen. Lakartidn. 69: 365-370 (1972). Gibbons, R. J. and van Houte, J.: Bacterial ad­ herence in oral microbial ecology. Ann. Rev. Microbiol. 29: 19-44 (1975). Glantz, P.-O.: On wettability and adhesiveness. Odont. Revy 20: suppl. 17 (1969).

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Guggenheim, B.: Extracellular polysaccharides and microbial plaque. Int. dent. J. 20: 657-678 (1970) . Guggenheim, B.; Mühlemann, H. R.; Regolati, B., and Schmid, R.: The effect of immunization against streptococci or glucosyl-transferases on plaque formation and dental caries in rats; in McHugh, Dental plaque (Livingstone, Edin­ burgh 1970). Guggenheim, B.; Regolati, B., and Mühlemann, H. R.: Caries and plaque inhibition by mutanase in rats. Caries Res. 6: 289-297 (1972). Hamilton, I. R.: Effects of fluoride on enzymatic regulation of bacterial carbohydrate metabo­ lism. Caries Res. 11: suppl. 1, pp. 262-291 (1977). Handelman, S. L.; Mills, J. R., and Hawes, R. R.: Caries incidence in subjects receiving long­ term antibiotic therapy. J. oral Ther. Pharm. 2: 338-342 (1962). Hardie, J. M. and Bowden, G. H.: The microbial flora of plaque: bacterial succession and isola­ tion considerations. Microbial Aspects dent. Caries 1: 63-87 (1976). Hugosson, A.; Koch, G.; Thilander, H., and Hoogendorn, H.: Lactoperoxidase in the preven­ tion of plaque. Odont. Revy 25: 69-80 (1974). Inoue, M.; Koga, T., and Morioka, T.: Scanning electron microscope study on the removal of artificial dental plaque treated with a bacter­ iolytic enzyme from Streptococcus globisporus - its synergistic effects with dextranase and ly­ sozyme. Abstract. J. dent. Hlth 24: 321 (1974). Johansen, J. R., Flötra, L. and Gjermo, P.: A clinical evaluation of the effect of Ascoxal-T on plaque formation and gingivitis. Acta odont. Scand. 28: 661-677 (1970). Kashket, S. and Guilmette, K. M.: Further evidence for the non-immunoglobulin nature of the bacterial aggregating factor in saliva. Caries Res. 12: 170-172 (1978). Kelstrup, J.; Funder-Nielsen, T. D., and M0llcr, E. N.: Enzymatic reduction of the colonization of Streptococcus mutans in human dental plaque. Acta odont. Scand. 31: 249-253 (1973). Keyes, P. H. and Shern, R.: Chemical adjuvants for control and prevention of dental plaque disease. J. Am. Soc. prev. Dent. 1: 18-22 (1971) .

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Anti-Plaque Therapeutics in Caries Prevention

Klcinbcrg, I.: The role of the dental plaque in car­ ies and inflammatory periodontal disease. J. Can. dent. Ass. 40: 56-66 (1974). Kleinberg, I.; Chatterjee, R.; Reddy, J., and Craw, D.: Effects of fluoride on the metabolism of the mixed oral flora. Caries Res. 11: suppl. 1, pp. 292-320 (1977). Lobene, R. R.: A clinical study of the effect of dextranase on human dental plaque. J. Am. dent. Ass. 82: 132-135 (1971). Lobene, R. R.; Soparkar, P. M.; Hein, J. W., and Quigley, G. A.: A study of the effects of anti­ septic agents and a pulsating irrigating device on plaque and gingivitis. J. Periodont. 43: 564-567 (1972). Loesche, W. J.: Chemotherapy of dental plaque infections. Oral Sci. Rev. 9: 65-107 (1975). Loesche, W. J.; Green, E.; Kenney, E. B., and Nafe, D.: Effect of topical kanamycin sulfate on plaque accumulation. J. Am. dent. Ass. 83: 1063-1065 (1971). Madsen, K. O.: Other organic compounds and dental caries: in Gould, Dietary chemicals vs. dental caries Am. Chem. Soc., Washington 1970. Magnusson, I.; Ericson, Th., and Pruitt, K.: Effect of salivary agglutinins on bacterial coloniza­ tion of tooth surfaces. Caries Res. 10: 113-122 (1976). Manly, R. S.: Inhibition of dental caries by denti­ frices - laboratory predictions vs. clinical results. Proc. Scient. Sect. Toilet Goods Assoc. No. 22, September 1954. Miller, W. D.: The microorganisms of the human mouth (Karger, Philadelphia 1890). Murayama, Y.; Wada, H.; Hayashi, H.; Uchida, T.; Yokomizo, I., and Hamada, S.: Effects of dextranase from Spicaria violaceae (IFO 6120) on the polysaccharides produced by oral strep­ tococci and on human dental plaque. J. dent. Res. 52: 658-667 (1973). Osugi, T.; Shibata, H.; Inoue, M., and Morioka, T.: Inhibition of plaque formation, caries de­ velopment and alveolar bone resorption in hamsters by a bacteriolytic enzyme from Streptococcus globisporus. Abstract. J. dent. Hlth 24: 372 (1974). Parsons, J. C.: Chemotherapy of dental plaque - a review. J. Periodont. 45: 177-186 (1974).

Frostell/Ericsson

Poole, D. F. G. and Newman, H. N.: Dental plaque and oral health. Nature 234: 329-331 (1971). Rölla, G.: Effects of fluoride on initiation of plaque formation. Caries Res. 11: suppl. 1, pp. 243-261 (1977). Rölla, G. and Meisen, B.: Desorption of protein and bacteria from hydroxyapatite by fluoride and monofluorophosphate. Caries Res. 9: 66-73 (1975). Sherp, H. W.: Dental caries. Prospects for preven­ tion. J. Am. Ass. Adv. Sci. 173: 1199-1205 (1971). Sims, W.: The concept of immunity in dental car­ ies. I. General considerations. Oral Surg. 30: 670-677 (1970). Sims, W.: The concept of immunity in dental car­ ies. II. Specific immune responses. Oral Surg. 34: 69-86 (1972). Stoppelaar de, J. D.; König, K. G.; Plasschaert, A. J. M., and Van der Hoeven, J. S.: Decreased cariogenicity of a mutant of Streptococcus mutans. Archs oral Biol. 16: 971-975 (1971). Strälfors, A.: Disinfection of dental plaques in man. Odont. Tidskr. 70: 183-203 (1962). Swenander-Lanke, L.: Influence on salivary sugar of certain properties of foodstuffs and individ­ ual oral conditions. Acta odont. scand. 15: suppl. 23 (1957). Taubman, M. A.: Role of immunization in dental disease: in Mergenhagen and Scherp, Compar­ ative immunology in the oral cavity, pp. 138-158 (USPHS, Washington 1973). Theilade, E. and Theilade, J.: Role of plaque in the etiology of periodontal disease and caries. Oral Sci. Rev. 9: 23-63 (1976). Walsh, J. P.: The relationships of surface active agents, the enamel surface and dental caries. Adv. Oral Biol. 1: 297-307 (1964). Williams, R. C. and Gibbons, R. J.: Inhibition of bacterial adherence by secretory immunoglob­ ulin A: a mechanism of antigen disposal. Sci­ ence 177: 697-699 (1972). Yokogawa, K.; Kawata, S.; Nishimura, S.; Ikeda, Y., and Yoshimura, Y.: Mutanolysin, bacter­ iolytic agent for cariogenic streptococci: par­ tial purification and properties. Antimicrob. Agents Chemothcr. 6: 156-165 (1974). Prof. Göran Frostell, Karolinska Institute, Department of Cariology, Box 3207, S-103 64 Stockholm (Sweden)

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Anti-plaque therapeutics in caries prevention.

Caries Res. 12 (Suppl. 1): 74-82 (1978) Anti-Plaque Therapeutics in Caries Prevention1 Goran Frostell and Yngve Ericsson Department of Cariology, Kar...
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