review on saliva

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162 THE JOURNAL OF PROSTHETIC DENTISTRY VOLUME 85 NUMBER 2 Saliva is a most valuable oral fluid that often is taken for granted. It is critical to the preservation and main- tenance of oral health, yet it receives little attention until quantity or quality is diminished. There has been much recent research on the topic of salivary dysfunc- tion as it relates to disease or as a side effect of certain medications. Saliva also has become useful as a nonin- vasive systemic sampling measure for medical diagnosis and research. Consequently, it is necessary for clini- cians to have a good knowledge base concerning the norm of salivary flow and function. This article reviews the biomedical literature on normal salivary composi- tion, flow, and function. A search of the literature was conducted by using the MEDLINE and Healthstar search engines (years 1944 through 1999). Articles from the primary, secondary, and tertiary literature were selected for inclusion on the basis of relevance and significance to the clinician. ORIGIN AND ANATOMY Saliva is a clear, slightly acidic mucoserous exocrine secretion. Whole saliva is a complex mix of fluids from major and minor salivary glands and from gingival crevicular fluid, which contains oral bacteria and food debris. 1,2 The major salivary glands include the paired parotid glands, which are located opposite the max- illary first molars, and the submandibular and sublin- gual glands, which are found in the floor of the mouth. Minor glands that produce saliva are found in the lower lip, tongue, palate, cheeks, and pharynx. 2 The terms major and minor refer to the anatomic size of the glands. Paradoxically, it could be argued that the minor salivary glands are the most important because of their protective components. 3 Major glands do pro- duce more saliva than minor glands, but the quality of content and thus the type of protection varies. The average daily flow of whole saliva varies in health between 1 and 1.5 L. Percentage contributions of the different salivary glands during unstimulated flow are as follows: 20% from parotid, 65% from sub- mandibular, 7% to 8% from sublingual, and less than 10% from numerous minor glands. Stimulated high flow rates drastically change percentage contributions from each gland, with the parotid contributing more than 50% of total salivary secretions. 3 The types of cells found in the salivary glands are acinar cells, various duct system cells, and myoep- ithelial cells. Acinar cells, in which saliva is first secreted, determine the type of secretion produced from the different glands. Secretion can be classified as serous, mucous, or mixed; serous secretions are produced mainly from the parotid gland, mucous secretions from the minor glands, and mixed serous and mucous secretions from the sublingual and sub- mandibular glands. 2 Duct system cells found in the salivary ducts are classified as intercalated, striated, and excretory. Intercalated duct cells are the first duct network connecting acinar secretions to the rest of the gland. These cells are not involved in the modification of electrolytes, as are the remaining duct cells. Striated cells are second in the network, functioning as electrolyte regulation in resorbing sodium. The final duct cells, the excretory duct cells, contribute by continuing sodium resorption and secreting potassium. Excretory duct cells are the last part of the duct network before saliva reaches the oral cavity. Myoepithelial cells, which are long cell processes wrapped around acinar cells, contract on stimulation to constrict the acinar. This function, secreting or “squeezing out” accumulating fluid, is the result of a purely neural process. 1,2,4 Understanding the source of saliva as well as the anatomy and location of salivary glands can impact the management of diminished flow in relationship to localized disease, systemic disease, radiation therapy, and/or salivary duct stones (sialoliths). 1,3,5 A review of saliva: Normal composition, flow, and function Sue P. Humphrey, RDH, MSEd, a and Russell T. Williamson, DMD b College of Dentistry, University of Kentucky, Lexington, Ky. An adequate supply of saliva is critical to the preservation and maintenance of oral tissue. Clinicians often do not value the many benefits of saliva until quantities are decreased. Much is written on the subject of salivary hypofunction, but little attention is paid to normal salivary flow and function. This article is a brief, up-to-date overview of the literature on the basics of normal salivary composition, flow, and function. A review of the literature was conducted using MED- LINE and Healthstar (1944 through 1999); articles were selected for inclusion on the basis of relevance and significance to the clinician. (J Prosthet Dent 2001;85:162-9.) a Assistant Professor, Department of Oral Health Practice, Chandler Medical Center. b Associate Professor, Department of Oral Health Practice, Chandler Medical Center.

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Page 1: Review on Saliva

162 THE JOURNAL OF PROSTHETIC DENTISTRY VOLUME 85 NUMBER 2

Saliva is a most valuable oral fluid that often is takenfor granted. It is critical to the preservation and main-tenance of oral health, yet it receives little attentionuntil quantity or quality is diminished. There has beenmuch recent research on the topic of salivary dysfunc-tion as it relates to disease or as a side effect of certainmedications. Saliva also has become useful as a nonin-vasive systemic sampling measure for medical diagnosisand research. Consequently, it is necessary for clini-cians to have a good knowledge base concerning thenorm of salivary flow and function. This article reviewsthe biomedical literature on normal salivary composi-tion, flow, and function. A search of the literature wasconducted by using the MEDLINE and Healthstarsearch engines (years 1944 through 1999). Articlesfrom the primary, secondary, and tertiary literaturewere selected for inclusion on the basis of relevanceand significance to the clinician.

ORIGIN AND ANATOMY

Saliva is a clear, slightly acidic mucoserous exocrinesecretion. Whole saliva is a complex mix of fluids frommajor and minor salivary glands and from gingivalcrevicular fluid, which contains oral bacteria and fooddebris.1,2 The major salivary glands include the pairedparotid glands, which are located opposite the max-illary first molars, and the submandibular and sublin-gual glands, which are found in the floor of themouth. Minor glands that produce saliva are found inthe lower lip, tongue, palate, cheeks, and pharynx.2The terms major and minor refer to the anatomic sizeof the glands. Paradoxically, it could be argued that theminor salivary glands are the most important becauseof their protective components.3 Major glands do pro-duce more saliva than minor glands, but the quality ofcontent and thus the type of protection varies.

The average daily flow of whole saliva varies inhealth between 1 and 1.5 L. Percentage contributionsof the different salivary glands during unstimulatedflow are as follows: 20% from parotid, 65% from sub-mandibular, 7% to 8% from sublingual, and less than10% from numerous minor glands. Stimulated highflow rates drastically change percentage contributionsfrom each gland, with the parotid contributing morethan 50% of total salivary secretions.3

The types of cells found in the salivary glands areacinar cells, various duct system cells, and myoep-ithelial cells. Acinar cells, in which saliva is firstsecreted, determine the type of secretion producedfrom the different glands. Secretion can be classifiedas serous, mucous, or mixed; serous secretions areproduced mainly from the parotid gland, mucoussecretions from the minor glands, and mixed serousand mucous secretions from the sublingual and sub-mandibular glands.2 Duct system cells found in thesalivary ducts are classified as intercalated, striated,and excretory. Intercalated duct cells are the firstduct network connecting acinar secretions to therest of the gland. These cells are not involved in themodification of electrolytes, as are the remainingduct cells. Striated cells are second in the network,functioning as electrolyte regulation in resorbingsodium. The final duct cells, the excretory duct cells,contribute by continuing sodium resorption andsecreting potassium. Excretory duct cells are the lastpart of the duct network before saliva reaches the oralcavity. Myoepithelial cells, which are long cellprocesses wrapped around acinar cells, contract onstimulation to constrict the acinar. This function,secreting or “squeezing out” accumulating fluid, isthe result of a purely neural process.1,2,4

Understanding the source of saliva as well as theanatomy and location of salivary glands can impact themanagement of diminished flow in relationship tolocalized disease, systemic disease, radiation therapy,and/or salivary duct stones (sialoliths).1,3,5

A review of saliva: Normal composition, flow, and function

Sue P. Humphrey, RDH, MSEd,a and Russell T. Williamson, DMDb

College of Dentistry, University of Kentucky, Lexington, Ky.

An adequate supply of saliva is critical to the preservation and maintenance of oral tissue.Clinicians often do not value the many benefits of saliva until quantities are decreased. Much iswritten on the subject of salivary hypofunction, but little attention is paid to normal salivary flowand function. This article is a brief, up-to-date overview of the literature on the basics of normalsalivary composition, flow, and function. A review of the literature was conducted using MED-LINE and Healthstar (1944 through 1999); articles were selected for inclusion on the basis ofrelevance and significance to the clinician. (J Prosthet Dent 2001;85:162-9.)

aAssistant Professor, Department of Oral Health Practice, ChandlerMedical Center.

bAssociate Professor, Department of Oral Health Practice, ChandlerMedical Center.

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COMPOSITION

Saliva is composed of a variety of electrolytes,including sodium, potassium, calcium, magnesium,bicarbonate, and phosphates. Also found in saliva areimmunoglobulins, proteins, enzymes, mucins, andnitrogenous products, such as urea and ammonia. Thesecomponents interact in related function in the followinggeneral areas: (1) bicarbonates, phosphates, and urea actto modulate pH and the buffering capacity of saliva; (2)macromolecule proteins and mucins serve to cleanse,aggregate, and/or attach oral microorganisms and con-tribute to dental plaque metabolism; (3) calcium,phosphate, and proteins work together as an antisolu-bility factor and modulate demineralization andremineralization; and (4) immunoglobulins, proteins,and enzymes provide antibacterial action.

The components listed above generally occur insmall amounts, varying with changes in flow, yet theycontinually provide an array of important functions. Itis important to stress that saliva, as a unique biologicfluid, must be considered as a whole that is greaterthan the sum of its parts.6 Salivary components, par-ticularly proteins, are multifunctional (performingmore than 1 function), redundant (performing similarfunctions but to different extents), and amphifunc-tional (acting both for and against the host).7 Recentresearch into the complex roles of salivary proteins andmucins support this theory; this research is discussedunder “Function.”8

Saliva is a very dilute fluid, composed of more than99% water. Saliva is not considered an ultrafiltrate ofplasma.5 Initially, saliva is isotonic, as it is formed inthe acini, but it becomes hypotonic as it travelsthrough the duct network. The hypotonicity ofunstimulated saliva allows the taste buds to perceivedifferent tastes without being masked by normal plas-ma sodium levels. Hypotonicity, especially during lowflow periods, also allows for expansion and hydrationof mucin glycoproteins, which protectively blanket tis-sues of the mouth.9 Lower levels of glucose,bicarbonate, and urea in unstimulated saliva augmentthe hypotonic environment to enhance taste.

The normal pH of saliva is 6 to 7, meaning that itis slightly acidic. The pH in salivary flow can rangefrom 5.3 (low flow) to 7.8 (peak flow). Major salivaryglands contribute most of the secretion volume andelectrolyte content to saliva, whereas minor salivaryglands contribute little secretion volume and most ofthe blood-group substances.3

FLOW

There is great variability in individual salivary flowrates. The accepted range of normal flow for unstim-ulated saliva is anything above 0.1 mL/min. Forstimulated saliva, the minimum volume for the

accepted norm increases to 0.2 mL/min. These num-bers have been projected from research on generalpopulations. Salivary flow is, however, a very individ-ualized measurement and ideally should be recordedas a base reference after the age of 15.3 Any unstimu-lated flow rate below 0.1 mL/min is consideredhypofunction.10 In a 1992 study, the critical rangeseparating persons with normal gland function fromthose with hypofunction was more precisely identi-fied as unstimulated whole salivary flow ratesbetween 0.12 and 0.16 mL/min.21 If individualizedbase rates have been established, then a 50% reductionin flow should be considered hypofunction.11

On average, unstimulated flow rate is 0.3 mL/min,3,5

with the average total for 16 hours of unstimulated flow(during waking hours) being 300 mL. Salivary flow dur-ing sleep is nearly zero. Stimulated flow rate is, atmaximum, 7 mL/min.3 Stimulated saliva is reported tocontribute as much as 80% to 90% of the average dailysalivary production.

The secretion of saliva is controlled by a salivarycenter composed of nuclei in the medulla,5 but thereare specific triggers for this secretion. Three types oftriggers, or stimuli, for this production are mechanical(the act of chewing), gustatory (with acid the moststimulating trigger and sweet the least stimulating),and olfactory (a surprisingly poor stimulus). Other fac-tors affecting secretion include psychic factors such aspain, certain types of medication, and various local orsystemic diseases affecting the glands themselves.2,5,12

Salivary glands are innervated by both sympathetic andparasympathetic nerve fibers. Various neurotransmit-ters and hormones stimulate different receptors,different salivary glands, and different responses.13

When sympathetic innervations dominate, the secre-tions contain more protein from acinar cells, whereaspredominant parasympathetic innervations produce amore watery secretion.3 Stimulation of 1 receptoroften enhances and complements another receptor.Therefore, the separation of contributing stimuli andresulting secretory products is not absolute.13 It mustbe emphasized that there is great individual variabilityin salivary stimulation and secretion from cell type tocell type, thereby affecting the content of saliva region-ally and as a whole.

Having distinguished between unstimulated andstimulated flow rates, it probably is more meaningfuland easier to measure whole saliva flow volume. Asstated earlier, whole saliva refers to the complex mix ofsalivary contents that includes stimulated and unstim-ulated saliva, gingival crevicular fluid, nonadherentoral bacteria and food debris, and traces of introducedchemicals or medicaments. Total daily flow of wholesaliva measures, on average, between 500 mL and 1.5 L,depending on the reference. There are daily and annualebbs and peaks in flow. Circadian (daily) low flow occurs

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during sleep, whereas peaks occur during high stimula-tion periods.14 Circannual (yearly) low flow occursduring the summer, whereas peak flow is during thewinter.3,12 Circadian flow variations affect not only flowbut also the concentration level of salivary componentssuch as salivary electrolytes and proteins.15

Salivary flow does not occur evenly throughout themouth. Regional variation in intraoral flow is site spe-cific, with the mandibular lingual being a site of highvolume and the maxillary anteriors and interproximalsbeing sites of low volume flow.3 These areas of high-er and lower volume flow regions have been referredto as “salivary highways and byways.”16 The regionalclearance rate of acid produced from bacteria is direct-ly influenced by regional variations in flow within themouth.17 Consequently, salivary byways are areas inwhich acid by-products may remain in longer contactwith oral structures unless mechanical means ofcleansing are used.16 Moreover, with varying amountsof components and secretions coming from differentglands, it is suggested that saliva provides differenttypes of protection in different locations intraorally.18

For example, parotid saliva contains amylase, proline-rich proteins, and agglutinins with minute amounts ofcystatins, lysozymes, and extraparotid glycoproteins.As a result, maxillary premolars exhibit higher countsof salivary agglutinins due to the proximity of theparotid duct. Sublingual saliva contributes high con-centrations of both types of mucins, MG1 and MG2,as well as high levels of lysozymes. Submandibularsaliva contains the largest amount of cystitis, whereaspalatine secretions offer MG1 mucins and relativelyhigh amylase concentrations.18 Considering that a0.1-mm-thick layer of saliva on a tooth is thinner thana layer of plaque, it is no surprise that the task ofcleansing oral structures cannot be completed suc-cessfully by saliva alone. A small amount of saliva, onaverage about 0.8 mL, remains in the mouth afterswallowing.3 This is referred to as residual volume.Dawe19 described a model for oral clearance, compar-ing it with an incomplete siphon. The smaller theamount of residual volume, the faster the clearancerate for the mouth.

Salivary dysfunction is not discussed at length inthis article, but reference to it must be made tounderstand the topic of normal flow and function.Dysfunction, more commonly called hypofunction,is difficult to assess, namely because of the existenceof a wide range of variations accepted as normal. Thediagnosis or assessment of salivary dysfunction is rel-atively subjective unless an individual base record ofsalivary flow has been established. About 30% of thepopulation reports some degree of dry mouth,which indicates that it is not an infrequent complaintor patient concern. Insufficient salivary flow resultsin 2 general, oral-related effects: (1) reduced prepa-

ration of food for digestion and taste, and (2) anincreased susceptibility of oral structures to dis-ease.20 A set of 4 easily collected clinical parametershas been described in recent research; these promotesuccessful identification of patients with salivarygland hypofunction. The parameters include evi-dence of dry lips; buccal mucosa dryness; lack ofsalivation on palpation; and a high total score on thedecayed, missing, or filled teeth index (DMFT).When all 4 parameters are scored collectively, posi-tive results may lead to further diagnostic evaluation,such as salivary flow rate measurements, minor sali-vary gland biopsy, and/or a sialography.21

Hypofunction of stimulated salivary flow is not anormal age-related change. Although decreased con-centrations of salivary mucins have been found withage in resting and stimulated whole human sali-va,22,23 research points to no substantial age-relatedchanges in the secretory responsiveness of salivarymucous cells.24,25 Many times, reduced flow in olderpatients is linked to side effects of prescription med-ications.3,26 Nutritional changes and deficiencies caninfluence salivary function as well. A modest reduc-tion in daily food intake may result in increasedsalivary protein, whereas severe caloric restrictionstend to reduce salivary flow, cell numbers, and sali-vary composition.27

A working knowledge of normal salivary flow isnecessary for the clinician discussing patient homecare instructions. Low flow during sleep mandates theneed to carefully cleanse the mouth before going tobed and after breakfast. The use of sugarless chewinggum or candy containing xylitol or sorbitol can berecommended as a means of stimulating extra salivaryflow to aid caries management and lubrication.3,28

Acidic and sweet taste stimuli are better choices astriggers for desired extra flow. Patients withdecreased salivary flow also should be made aware ofthe necessity to comply with suggested oral hygieneregimens after exposure to acid-producing foodsources. Recommendations for professional andhome fluoride treatments should be considered care-fully for patients with salivary dysfunction, especiallythose with high caries rates and exposed root sur-faces. The successful use of removable prostheses bya patient also may be affected dramatically bydecreased salivary flow.

FUNCTION

Salivary function can be organized into 5 majorcategories that serve to maintain oral health and cre-ate an appropriate ecologic balance: (1) lubricationand protection, (2) buffering action and clearance,(3) maintenance of tooth integrity, (4) antibacterialactivity, and (5) taste and digestion.16,29 As statedearlier, salivary components work in concert in over-

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lapping, multifunctioning roles, which can be simulta-neously beneficial and detrimental.7

As a seromucous coating, saliva lubricates and pro-tects oral tissues, acting as a barrier against irritants.These irritants include, but are not limited to, proteo-lytic and hydrolytic enzymes produced in plaque,potential carcinogens from smoking and exogenouschemicals, and desiccation from mouth breathing.5The best lubricating components of saliva are mucinsthat are excreted from minor salivary glands. Mucinsare complex protein molecules that are present pre-dominantly in 2 molecular weight types31,32 andformed by polypeptide chains that stick together.These mucins have the properties of low solubility,high viscosity, high elasticity, and strong adhesiveness.Any intraoral contact between soft tissues, betweensoft tissues and teeth, or between soft tissues and pros-theses benefits from the lubricating capability of salivasupplied largely by these mucins.3 Mastication, speech,and swallowing all are aided by the lubricating effectsof mucins.32

Mucins also perform an antibacterial function byselectively modulating the adhesion of microorganismsto oral tissue surfaces, which contributes to the controlof bacterial and fungal colonization. Secretions fromthe sublingual and submandibular glands contain ahigh-molecular-weight, highly glycosylated mucin(MG1) and a low-molecular-weight, single-glycosylatedpeptide chain mucin (MG2).31,32 The importance ofthese 2 major mucins has been the focus of muchresearch in the last 2 decades. MG1 adsorbs tightly tothe tooth and thereby contributes to the enamel pelli-cle, which protects the tooth from acid challenges.MG1 forms heterotypic complexes with other salivaryproteins such as amylase, proline-rich proteins,statherin, and histatins, simultaneously attracting theattachment of certain bacteria and providing a short-term nutrient source for bacteria.30 MG2 binds toenamel but is displaced easily. It promotes the aggre-gation and clearance of oral bacteria, includingstreptococci mutans.33,34 In the saliva of caries-resis-tant patients, MG2 predominates, whereas the level ofMG1 is higher in caries-susceptible patients.31 Animportant part of the multifunctional role of salivarymucins in preserving mucosal integrity is their abilityto regulate intercellular calcium levels.31 As a part ofthe enamel pellicle, mucins help initiate bacterial colo-nization by promoting the growth of benigncommensal oral flora, forming a protective barrier andlubrication against excessive wear, providing a diffu-sion barrier against acid penetration, and limitingmineral egress from the tooth surface.9 The results ofresearch clearly indicate that salivary mucins perform avariety of functions essential to maintaining a stableoral defense.32

Buffering action and clearance are a second func-

tion of saliva through the following components:bicarbonate, phosphate, urea, and amphoteric proteinsand enzymes. Bicarbonate is the most importantbuffering system. It diffuses into plaque and acts as abuffer by neutralizing acids. Moreover, it generatesammonia to form amines, which also serve as a bufferby neutralizing acids.35 More than 90% of the nonbi-carbonate buffering ability of saliva is attributed tolow-molecular-weight, histidine-rich peptides.20 Urea,another buffer present in saliva, releases ammonia afterbeing metabolized by plaque and thus increases plaquepH.27 The buffering action of saliva works more effi-ciently during stimulated high flow rates but is almostineffective during periods of low flow with unstimulat-ed saliva.2,3 Phosphate is likely to be important as abuffer only during unstimulated flow.36

The pH of saliva may not be as important a measurefor buffering action on caries as the pH of plaque,which saliva modifies.2 Remaining fermentable carbo-hydrates and the buffering capacity of saliva affectplaque pH, unless the pH of the plaque is too low forbacterial enzymes to function. The resting pH ofplaque (that is, the pH of plaque 2 to 2.5 hours afterthe last intake of exogenous carbohydrates) is 6 to7.3,37 The pH rises during the first 5 minutes after theintake of most foods. The pH then falls to its lowestlevel, to 6.1 or lower, approximately 15 minutes afterfood consumption. Unless there is additional ingestionof fermentable carbohydrates, the pH of plaque grad-ually returns to its resting pH of 6 to 7.38-40 Thus,salivary buffering, clearance, and flow rate work inconcert to influence intraoral pH.39 As stated earlier,salivary flow can be augmented by the stimulus ofchewing as well as by the muscular activity of the lipsand tongue.29,35 With stimulated additional flow,chewing products (such as gum) that contain no fer-mentable carbohydrates can aid in the modulation ofplaque pH. Sugar-free sweeteners such as xylitol andsorbitol should be recommended for use without fearof promoting caries. Indeed, research has shown thatthe use of gum containing xylitol or sorbitol reducesplaque accumulation and gingival inflammation andenhances remineralization potential.41 Taking intoaccount the time frame for changes in plaque pH relat-ed to the ingestion of fermentable carbohydrates,dentists should recommend that patients, especiallythose who are caries-prone, brush soon after the intakeof cariogenic meals and snacks.

Maintaining tooth integrity is a third function ofsaliva, one that facilitates the demineralization andremineralization process. Demineralization occurswhen acids diffuse through plaque and the pellicleinto the liquid phase of enamel between enamel crys-tals. Resulting crystalline dissolution occurs at a pH of5 to 5.5, which is the critical pH range for the devel-opment of caries.3 Dissolved minerals subsequently

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diffuse out of the tooth structure and into the salivasurrounding the tooth. The buffering capacity of sali-va greatly influences the pH of plaque surroundingthe enamel, thereby inhibiting caries progression.37

Plaque thickness and the number of bacteria presentdetermine the effectiveness of salivary buffers.

Remineralization is the process of replacing lostminerals through the organic matrix of the enamel tothe crystals. Supersaturation of minerals in saliva is crit-ical to this process. The high salivary concentrations ofcalcium and phosphate, which are maintained by sali-vary proteins, may account for the maturation andremineralization of enamel.2 Statherin, a salivary pep-tide, contributes to the stabilization of calcium andphosphate salts solution, serves as a lubricant to protectthe tooth from wear, and may initiate the formation ofthe protective pellicle by binding to hydroxyapatite.3,6

Proteins in the protective pellicle, such as statherin,histatins, cystatins, and proline-rich proteins, are toolarge to penetrate enamel pores. Therefore, theyremain on the surface, bound to hydroxyapatite, to aidin controlling crystalline growth of the enamel byallowing the penetration of minerals into the enamelfor remineralization and by limiting mineral egress.6,34

This control of precipitation and mineral egressenhances the stability of hydroxyapatite in the outertooth structure.42 Low-molecular-weight protein frac-tions, thought to be derived from the proteolyticprocessing of larger proteins, are likely to be inexchange with dental plaque fluid. These protein frac-tions help adjust and augment remineralization,microbial attachment, and plaque metabolism at thetooth-saliva interface.43,44

The presence of fluoride in saliva speeds up crystalprecipitation, forming a fluorapatite-like coating moreresistant to caries than the original tooth structure. Inthat sense, small amounts of demineralization havebeen suggested as advantageous for the tooth becauseenamel components of magnesium and carbonate arereplaced with the stronger, more caries-resistant fluor-apatite crystals.3 Fluoride in salivary solution works toinhibit dissolution of apatite crystals.

The contribution of saliva to the demineralization-remineralization process points to the importance ofmonitoring salivary flow, especially in patients takingmultiple medications or having systemic entities thatdecrease salivary flow. For patients with exposed rootsurfaces or with recurrent or incipient carious lesions,fluoride supplementation can promote remineraliza-tion. Salivary stimulants and substitutes also should beencouraged for patients with salivary hypofunction.Researchers currently are investigating a method togenetically engineer salivary proteins and other salivarycomponents for use in future artificial salivas.7 Homecare for persons with decreased salivary flow becomesa time-consuming process because plaque and any

food material tenaciously cling to hard and soft tissuesurfaces in relatively dry environments. Even profes-sional therapy for patients with extreme salivarydysfunction is a challenge because of tissue desiccationand subsequent lack of ease in manipulating instru-ments and materials under such conditions. Cliniciansshould resist the temptation to “overexplore” whitespot lesions. Excessive manipulation of the crystallinestructure may interfere with further remineralizationof the area.3

A fourth function of saliva is its antibacterial activity.Salivary glands are exocrine glands, and, as such, secretefluid containing immunologic and nonimmunologicagents for the protection of teeth and mucosal surfaces.Immunologic contents of saliva include secretory IgA,IgG, and IgM. Nonimmunologic salivary contents areselected proteins, mucins, peptides, and enzymes.Secretory IgA, the largest immunologic component ofsaliva, is an immunoglobulin produced by plasma cellsin connective tissues and translocated through the ductcells of major and minor salivary glands. IgA, whileactive on mucosal surfaces, also acts to neutralize virus-es, serves as an antibody to bacterial antigens, and worksto aggregate or clump bacteria, thus inhibiting bacterialattachment to host tissues.6,45 Other immunoglobulinspresent in saliva are in low quantities and probably comefrom gingival crevicular fluid.2 It seems unlikely thathost complement response could act generally in theoral fluid.3 IgA itself does not activate complement,5but oral fluids can be augmented by gingival crevicularfluid host complement components when gingivitis ispresent around existing teeth.1,29

Immunologic and nonimmunologic antibacterialsalivary content come from 2 different sources—namely, plasma and ductal cells—with differentresponses to stimulation and different content levels.Nonimmunologic antibacterial salivary contents suchas proteins, mucins, peptides, and enzymes (lactofer-rin, lysozyme, and peroxidase), all products of acinargland cells, help protect teeth against physical,chemical, and microbial insults.15 MG2, the low-molecular-weight mucin, and IgA complex bindmucosal pathogens with greater affinity than eitherMG2 or IgA alone.46 Lactoferrin, produced in inter-calated ductal cells, binds ferric iron in saliva. Thisprocess makes ferric iron unavailable as a food sourcefor microbes, such as cariogenic streptococci, thatneed iron to remain viable.2 This process of starvingbacteria of vital nutrients is called nutritional immu-nity.47 Lactoferrin exhibits another antimicrobialeffect not related to its iron-binding ability via thesensitivity of Streptococcus mutans to lactoferrin.48

Lysozymes, derived from the basal cells of striatedducts in parotid glands, split bacterial cell walls, lead-ing to the destruction and inhibition of bacterialgrowth.5,49 Moreover, lysozymes promote the clear-

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ance of bacteria through aggregation. Gingival crevic-ular fluid also contributes lysozymes from plasma.6Peroxidase, also known as sialoperoxidase or lactoper-oxidase, catalyzes bacterial metabolic by-products withthiocynate, which is highly toxic to bacterial sys-tems.1,3 Secreted by acinar cells, peroxidaseadditionally protects mucosa from the strong oxidiz-ing effects of hydrogen peroxide produced by oralbacteria.6 Cystatins, a family of cysteine-containingproteins, have a minor role in the regulation of salivarycalcium. But the main action of cystatins may be toinhibit cysteine-proteinase involved in the pathogene-sis of periodontal disease.31

Finally, proteins such as glycoproteins, statherins,agglutinins, histadine-rich proteins, and proline-richproteins work to aggregate bacteria. This “clumping”process, as described earlier, reduces the ability of bac-teria to adhere to hard or soft tissue intraoral surfacesand thereby controls bacterial, fungal, and viral colo-nization.35 As a whole, protein content increasesproportionally with increasing flow rate.2 But salivaryprotein concentrations, like other salivary compo-nents, may also be subject to circadian variations andaffected by stress, inflammation, infection, and hor-monal changes. In addition, protein content variesamong persons, exhibits different polymorphic pheno-types, and can exhibit strain-species differences inprotein-microbial interactions.15

It is a paradox that, although saliva has numerousantibacterial functions, it also supports the selectivebacterial growth of noncariogenic microflora.50

Glucose levels in saliva are too low to explain this phe-nomenon.1,3 Just as the content of saliva varies indifferent parts of the mouth, so varies the compositionof pellicle formed in different parts of the mouth. Thismay be important in the establishment of bacteria andtooth-related disease patterns from one area of themouth to another.51

The concept of saliva’s antibacterial activity high-lights the clinical value of stimulating natural saliva,especially in patients with decreased function. Salivasubstitutes are extremely important for lubrication andhelpful for oral clearance and tooth integrity, but theyoffer little that can compare with the protection givenby natural salivary components. Because salivary com-ponents are considered multifunctional (that is, having“built-in” compensatory redundant antibacterial prop-erties) and amphifunctional, depending on theintraoral environment or the molecule, the develop-ment of an effective artificial saliva is a difficult task.7,52

A fifth and final function of saliva is to enhance tasteand begin the digestive process. The hypotonicity ofsaliva enhances the tasting capacity of salty foods andnutrient sources. This enhanced tasting capabilitydepends on the presence of protein and gustin, whichbind zinc.2 Saliva has an early, limited role in total

digestion by beginning the breakdown of starch withamylase, a major component of parotid saliva that ini-tially dissolves sugar.16,29 The contribution of saliva tostarch breakdown is limited because most of the diges-tion of starch results from pancreatic amylase, notsalivary amylase.5 Salivary enzymes also initiate fatdigestion.53 More importantly, saliva serves to lubri-cate the food bolus, which aids in swallowing.1,27,54

When one considers the contribution of saliva to tasteand early digestion, it becomes clear that artificial sup-plements would be difficult to develop.

RESEARCH APPLICATIONS

Many areas of research involving salivary compo-nents and functions are in progress for local andsystemic disease diagnosis, treatment, and prevention.The value of saliva undoubtedly will continue toincrease because it serves as an easily collected, nonin-vasive source of information. Reflective of the status ofhealth in the body, salivary samples can be analyzedfor: (1) tissue fluid levels of naturally, therapeutically,and recreationally introduced substances; (2) emotion-al status; (3) hormonal status; (4) immunologic status;(5) neurologic status; and (6) nutritional/metabolicinfluences.55

Saliva already is used to aid in the diagnosis of den-tal disease. Examples include caries risk assessment,periodontal disease genotypes, and identificationmarkers for periodontal disease, salivary gland diseaseand dysfunction, and candida infections. Salivary col-lections are used for diagnostic determinants for viraldiseases, sarcoidosis, tuberculosis, lymphoma, gastriculcers and cancers, liver dysfunction, and Sjogren’ssyndrome.55-58 Saliva also is being used to monitorlevels of polypeptides, steroids, antibodies, alcohol,and various other drugs. Research currently is beingconducted to determine the value of saliva as a diag-nostic aid for cancer and preterm labor.56,57 Anotherarea of research involves the possible regenerativeproperties and functions of growth factors found insaliva, such as epidermal growth factor and transform-ing growth factor. Evidence suggests that these growthfactors play a role in wound healing and the mainte-nance of oral and systemic health.20,59

The multifunctional roles of salivary components con-tinue to represent a very focused area of dental research.Can the redundant and synergistic effects of salivary pro-teins be used to further enhance remineralization? Couldthe salivary antibacterial factors be targeted to positivelyalter the biofilm community in plaque? Can salivary con-stituents more selectively control bacterial adherence andaggregation? Can the buffering system of saliva effective-ly and selectively be enhanced? Can salivary componentsbe reproduced or replaced by new developments in arti-ficial saliva? Questions such as these are being addressedthrough continuing research efforts.

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The knowledge of normal salivary composition, flow,and function is extremely important on a daily basiswhen treating patients. Dental health professionals spenduntold hours removing this precious natural resource toperform therapy with little regard to its value until flowis significantly diminished. Whether saliva occurs inquantities large or small, recognition should be given tothe many contributions it makes to the preservation andmaintenance of oral and systemic health.

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4. Garrett JR. The proper role of nerves in salivary secretion: a review. J DentRes 1987;66:387-97.

5. Grant DA, Stern IB, Listgarten MA, editors. Saliva. In: Periodontics. 6th ed.St Louis: CV Mosby; 1988. p.135-46.

6. Dowd FJ. Saliva and dental caries. Dent Clin North Am 1999;43:579-97. 7. Levine MJ. Development of artificial salivas. Crit Rev Oral Biol Med

1993;4:279-86.8. Levine MJ. Salivary macromolecules. A structure/function synopsis. Ann

NY Acad Sci 1993;694:11-6.9. Tabak LA, Levine MJ, Mandel ID, Ellison SA. Role of salivary mucins in the

protection of the oral cavity. J Oral Pathol 1982:11:1-17.10. Screebny LM, Valdini A. Xerostomia. A neglected symptom. Arch Intern

Med 1987:147:1333-7.11. Ship JA, Fox PC, Baum BJ. How much saliva is enough? ‘Normal’ function

defined. J Am Dent Assoc 1991;122:63-9.12. Shannon IL. The biochemistry of human saliva in health and disease. In:

Rowe WH, editor. Salivary glands and their secretion. Ann Arbor:University of Michigan Press; 1972. p.92-121.

13. Culp DJ, Graham LA, Latchney LR, Hand AR. Rat sublingual gland as amodel to study glandular mucous cell secretion. Am J Physiol1991;260:C1233-44.

14. Dawes C. Rhythms in salivary flow rate and composition. Int J Chronobiol1974;2:253-79.

15. Rudney JD. Does variability in salivary protein concentrations influenceoral microbial ecology and oral health? Crit Rev Oral Biol Med1995;6:343-67.

16. Moss S. Clinical implications of recent advances in salivary research. JEsthet Dent 1995;7:197-203.

17. Dawes C, MacPherson LM. The distribution of saliva and sucrose aroundthe mouth during the use of chewing gum and the implications for site-specificity of caries and calculus deposition. J Dent Res 1993:72:852-57.

18. Veerman EC, van den Keybus PA, Vissink A, Nieuw Amerongen AV.Human glandular salivas: their separate collection and analysis. Eur J OralSci 1996;104:346-52.

19. Dawes C. A mathematical model of salivary clearance of sugar from theoral cavity. Caries Res 1983;17:321-34.

20. Mandel ID. The role of saliva in maintaining oral homeostasis. J Am DentAssoc 1989;119:298-304.

21. Navazesh M, Christensen C, Brightman V. Clinical criteria for the diagno-sis of salivary gland hypofunction. J Dent Res 1992;71:1363-9.

22. Navazesh M, Mulligan RA, Kipnis V, Denny PA, Denny PC. Comparison ofwhole saliva flow rates and mucin concentrations in healthy Caucasianyoung and aged adults. J Dent Res 1992;71:1275-8.

23. Denny PC, Denny PA, Klauser DK, Hong SH, Navazesh M, Tabak LA. Age-related changes in mucins from human whole saliva. J Dent Res1991;70:1320-7.

24. Culp DJ, Richardson LA. Regulation of mucous acinar exocrine secretionwith age. J Dent Res 1996;75:575-80.

25. Aguirre A, Testa-Weintraub LA, Banderas JA, Haraszthy GG, Reddy MS,Levine MJ. Sialochemistry: a diagnostic tool? Crit Rev Oral Biol Med1993;4:343-50.

26. Ship JA, Nolan NE, Puckett SA. Longitudinal analysis of parotid and sub-

mandibular salivary flow rates in healthy, different-aged adults. J GerontolA Biol Sci Med Sci 1995;50:M285-9.

27. Johnson DA. Regulation of salivary glands and their secretions by mastica-tory, nutritional and hormonal factors. In: Scribney LM, editor. The salivarysystem. Boca Raton, FL: CBC Press; 1987. p.136-55.

28. Isokangas P, Tiekso J, Alanen P, Makinen KK. Long-term effect of xyli-tol chewing gum on dental caries. Community Dent Oral Epidemiol1989;17:200-3.

29. Mandel ID. The function of saliva. J Dent Res 1987;66:623-7.30. Iontcheva I, Oppenheim FG, Troxler RF. Human salivary mucin MG1

selectively forms heterotypic complexes with amylase, proline-rich pro-teins, statherin, and histatins. J Dent Res 1997;76:734-43.

31. Slomiany BL, Murty VL, Poitrowski J, Slomiany A. Salivary mucins in oralmucosal defense. Gen Pharmacol 1996;27:761-71.

32. Tabak LA. Stucture and function of human salivary mucins. Crit Rev OralBiol Med 1990;1:229-34.

33. Levine MJ, Reddy MS, Tabak LA, Loomis RE, Bergey EJ, Jones PC, et al.Structural aspects of salivary glycoproteins. J Dent Res 1987;66:436-41.

34. Scannapieco FA, Levine MJ. Salivary mucins and dental plaque formation.In: Bowen WH, Tabak LA, editors. Cariology for the nineties. Rochester,NY: University of Rochester Press; 1993. p.87-105.

35. Mandel ID. Impact of saliva on dental caries. Compend Suppl 1989:S476-81.

36. Lagerlof F, Oliveby A. Caries-protective factors in saliva. Adv Dent Res1994;8:229-38.

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38. Edgar WM. The role of saliva in the control of pH changes in human den-tal plaque. Caries Res 1976;10:241-54.

39. Bibby BG, Mundorff SA, Zero DT, Almekinder KJ. Oral food clearance andthe pH of plaque and saliva. J Am Dent Assoc 1986;112:333-7.

40. Rugg-Gunn AJ, Edgar WM, Geddes DA, Jenkins GN. The effect of differ-ent meal patterns upon plaque pH in human subjects. Br Dent J1975;139:351-6.

41. Steinberg LM, Odusola F, Mandel ID. Remineralizing potential, antiplaqueand antigingivitis effects of xylitol and sorbitol sweetened chewing gums.Clin Prev Dent 1992;14:31-4.

42. Richardson CF, Johnsson M, Raj PA, Levine MJ, Nancollas GH. The influ-ence of histatin-5 fragments on the mineralization of hydroxyapatite. ArchOral Biol 1993;38:997-1002.

43. Margolis HC. Enamel-plaque fluid interactions. In: Bowen WH, Tabak LA,editors. Cariology for the nineties. Rochester, NY: University of RochesterPress; 1993. p.173-81.

44. Perinpanayagam HE, ManWuyckhuyse BS, Ji ZS, Tabak LA. Charact-erization of low-molecular-weight peptides in human parotid saliva. JDent Res 1995;74:345-50.

45. McNabb PC, Tomasi TB. Host defense mechanisms at mucosal surfaces.Annu Rev Microbiol 1981;35:447-96.

46. Biesbrock AR, Reddy MS, Levine MJ. Interaction of salivary mucin-secre-tory immunoglobulin A complex with mucosal pathogens. Infect Immun1991;59:3492-7.

47. Mandel ID. Nonimmunologic aspects of caries resistance. J Dent Res1976;55:C22-31.

48. Lassiter MO, Newsome AL, Sams LD, Arnold RR. Characterization of lacto-ferrin interaction with Streptococcus mutans. J Dent Res 1987;66:480-5.

49. Pollock JJ, Lotardo S, Gavai R, Grossbard BL. Lysozyme-protease-inorgan-ic monovalent anion lysis of oral bacterial strains in buffers and stimulatedwhole saliva. J Dent Res 1987;66:467-74.

50. Cowman RA, Schaefer SJ, Fitzgerald RJ. Specificity of utilization ofhuman salivary proteins for growth by oral streptococci. Caries Res1979;13:181-9.

51. Carlen A, Borjesson AC, Nikdel K, Olsson J. Composition of pelliclesformed in vivo on tooth surfaces in different parts of the dentition, and invitro on hydroxyapatite. Caries Res 1998;32:447-55.

52. Tenovuo J. Antimicrobial function of human saliva—how important is it fororal health? Acta Odontol Scand 1998;56:250-6.

53. Valdez IH, Fox PC. Interactions of the salivary and gastrointestinal systems.I. The role of saliva in digestion. Dig Dis 1991;9:125-32.

54. Hatton MN, Loomis RE, Levine MJ, Tabak LA. Masticatory lubrication. Therole of carbohydrate in the lubricating property of a salivary glycoprotein-albumin complex. Biochem J 1985;230:817-20.

55. Mandel ID. Salivary diagnosis: promises, promises. Ann NY Acad Sci1993;694:1-10.

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56. Slavkin HC. Toward molecularly based diagnostics for the oral cavity. J AmDent Assoc 1998;129:1138-43.

57. Malamued D. Saliva as a diagnostic fluid. Br Med J 1992;305:207-8.58. Mandel ID. A contemporary view of salivary research. Crit Rev Oral Biol

Med 1993;4:599-604.59. Zelles T, Purushotham KR, Macauley SP, Oxford GE, Humphreys-Beher MG.

Saliva and growth factors: the fountain of youth resides in us all. J Dent Res1995;74:1826-32.

Reprint requests to:DR SUE P. HUMPHREY, RDH,MSED

DEPARTMENT OF ORAL HEALTH PRACTICE, ROOM D-440COLLEGE OF DENTISTRY, UNIVERSITY OF KENTUCKY

CHANDLER MEDICAL CENTER

LEXINGTON, KY 40536-0297FAX: (606)257-1847E-MAIL: [email protected]

Copyright © 2001 by The Editorial Council of The Journal of ProstheticDentistry.

0022-3913/2001/$35.00 + 0. 10/1/113778

doi:10.1067/mpr.2001.113778

Passivity of fit and marginal opening in screw- or cement-retained implant fixed partial denture designsGuichet DL, Caputo AA, Choi H, Sorensen JA. Int J OralMaxillofac Implants 2000;15:239-46.

Purpose. Early designs of implant-supported restorations called for screw retention of the pros-thesis to allow for its retrieval. With increasing predictability of the osseointegration process, therehas been an increase in the usage of nonretrievable prosthesis designs that use cement retentionof the final restoration. This study compared the marginal fit of prostheses to support abutmentswhen restorations were cemented versus screw-retained. In addition, the study evaluated thestress patterns in a photoelastic model of the implants with the 2 different methods of prosthesisretention.Material and methods. A simulated mandibular model was created with 10 mm implants(Branemark System, Noble Biocare, Yorba Linda, Calif.) in the positions of the left first and sec-ond premolar and first molar teeth. Five prostheses were fabricated to fit to EP ConicalAbutments (Implant Innovations Inc, Palm Beach Gardens, Fla.) for the screw-retained design,and 5 prostheses were fabricated to fit to EP 2-piece abutment posts (Implant Innovations Inc,Palm Beach Gardens, Fla.) for the cement-retained design. Marginal integrity was assessed usinga traveling microscope (Gaertner, Chicago, Ill.) before cementation or screw tightening and againafter cementation and screw tightening. Photoelastic models were assessed for both types of pros-thetic restorations with stress concentration ranked for comparison purposes.Results. There were no significant differences in marginal openings before cementation, beforescrew tightening, or after cementation. Marginal closure did occur when the retaining screwswere tightened, resulting in a significant improvement of fit (P<.05). Photoelastic analysis showedhigher stress concentration with the screw-retained restorations.Discussion. Both methods of prosthesis connection have advantages and disadvantages. Passivityof fit has been described as an important factor for maintenance of osseointegration, but this con-cept recently has been questioned. Ongoing research on this topic and on methods to improvefit was suggested. 35 References. —SE Eckert

Noteworthy Abstractsof theCurrent Literature