aoh

aWm. Wrigley Jr. Company, 35bDepartment of Community DeSan Antonio, TX, USAcDepartments of Dental DiagnCenter at San Antonio and GeSouth Texas Veterans Health

Received 15 October 2004; received in

KEYWORDSSaliva;Aging;Diabetes;

population-based study cohort (NZ1130) indicate that there is an age-relateddecline in saliva output for unstimulated whole, stimulated parotid, unstimulated

saliva as a medium, fewer have studied saliva froma comprehensive perspective, and considered therole of this fluid in maintaining the health, comfort

Journal of Dentistry (2005) 33, 223233Introduction

The aim of this paper is to present an update andsynopsis of saliva and salivary gland function and

effects on oral health, including dental caries, aswell as to present some of our own data obtainedfrom recent work on aging, systemic disease andsaliva output. Although many workers have studiedsubmandibular/sublingual and stimulated submandibular/sublingual saliva, as wellas some compositional alterations in anti-microbial and other proteins. Some ofthese alterations also appear to be specific for certain age-related medicalconditions, such as diabetes mellitus.

Conclusions. These studies and data presented confirm the importance of saliva inmaintaining a healthy oral environment; the practitioner is encouraged to considersaliva output and medical conditions that may compromise it as part of routinedental treatment planning.q 2004 Elsevier Ltd. All rights reserved.Hypertension35 S. Ashland Avenue, Chicago, IL 60609, USAntistry, University of Texas Health Science Center at San Antonio,

ostic Science and Community Dentistry, University of Texas Health Scienceriatric Research, Education and Clinical Center, Audie L. Murphy Division,Care System, San Antonio, TX 78284, USA

revised form 15 October 2004; accepted 18 October 2004

Summary Objective. The aim is to present a review of the literature on humansaliva composition, flow rates and some of the health benefits of saliva, withemphasis on studies from our laboratory that have looked at effects of age and age-related diseases on saliva output and composition.

Data. Saliva influences oral health both through its non-specific physico-chemicalproperties, as well as through more specific effects. The proline-rich proteins,statherin and the histatins are salivary proteins that influence calcium phosphatechemistry, initial plaque formation and candida infection. Increases or decreases inmastication may affect saliva output. Our cross-sectional studies of saliva in a largeHealth benefits of saliva:

Michael W.J. Doddsa,*, Dorthea A. Jreview

nsonb, Chih-Ko Yehc

www.intl.elsevierhealth.com/journals/jdenand comprehensive recent review by Sreebny1

0300-5712/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.doi:10.1016/j.jdent.2004.10.009

650 2335.E-mail address: mdodds@wrigley.com (M.W.J. Dodds).and well-being of the human organism. An excellent* Corresponding author. Tel.: C1 773 650 7678; fax: C1 773

exemplifies this approach, and the reader is

initial secretion of an aqueous plasma-like primaryfluid by the acinar cells and its subsequentmodification during passage through the water-

Since, a healthy flow of saliva is deemed critical

They are multifunctional proteins, with separatebacterial and hydroxyapatite-binding domains and

M.W.J. Dodds et al.224impermeable ductal cell system. Secretion iscontrolled by the autonomic nervous system viasignal transduction systems that couple receptorstimulation to ion transport and protein secretorymechanisms. The volumes of saliva produced varydepending on the type and intensity of stimulation,the largest volumes occurring with cholinergicstimulation. Neurotransmitters released inresponse to secretory stimuli bind to specificprotein receptors on the acinar cell membrane.This causes alterations in membrane-bound G-proteins and a subsequent series of intracellularsecond messenger events is initiated. In the case ofmuscarinic cholinergic stimulation, the signal trans-duction system involves release of calcium fromintracellular stores by inositol triphosphate (IP3)and the subsequent activation of a variety of ionchannels and transport systems, ultimately leadingto the trans-epithelial movement of water.47directed to this and other reviews referenced.The effects of profound loss of salivary gland

function are well known, such as in the case ofradiation-induced xerostomia, or Sjogrens syn-drome. However, more subtle functional deficitsmay be less obvious. One reason for this apparentparadox may be the principle of a functionalreserve capacity of the salivary glands. Simplyput, most individuals are able to produce moresaliva when stimulated than could ever be requiredfor what are usually listed as the functions of thisparticular body fluid. Similarly, there is apparentfunctional redundancy in the ability of varioussalivary proteins to adsorb to hydroxyapatite andto bind and agglutinate oral bacteria.2,3 Perhapsthese facts in themselves point to the overwhelm-ing importance of saliva in homeostasis andprotection of the organism from deleterious extrin-sic influences.

Basic concepts of saliva secretion

Saliva is produced by three pairs of major salivaryglands (parotid, submandibular and sublingual) plusnumerous minor salivary glands. Salivary glandsconsist of highly specialised epithelial-derived cellswith two fairly well defined morphological andfunctional segments, that is, the end pieces (aciniand intercalated ducts) and a system of glandularducts of varying complexity. Saliva secretion isgenerally accepted to be a two-stage process, withwhen adsorbed to the tooth surface, may providehighly specific sites of attachment for certain oralbacteria. It has been suggested that adsorption ofPRPs to hydroxyapatite/enamel causes a confor-mational change in the protein, thus exposingOrganic constituents of saliva

Saliva contains a wide variety of proteins which areunique to this fluid and which have biologicfunctions of particular importance to oral health.Many of these proteins contain high levels (3540%)of proline, and are therefore, designated proline-rich proteins (PRPs). PRPs, which comprise almost70% of the total protein content of human parotidsaliva, are further divided into three groups basedon charge and degree of glycosylation: acidic, basicand glycosylated basic PRPs.12 Since amylasecomprises most of the remainder of the totalprotein content of parotid saliva, the other proteins(such as lysozyme, lactoferrin, peroxidase, andsecretory IgA) that have received more attention inattempted linkages between saliva and oral healthare, in fact, relatively minor components.

The acidic PRPs exhibit genetic heterogeneity13

and are found in the acquired enamel pellicle.14for the maintenance of both oral and generalhealth8 factors that affect the development, func-tion and state of differentiation of salivary glandcells would have an effect on the health and well-being of the whole organism.

Salivary composition

Inorganic constituents of saliva

Although the primary secretion is a plasma ultra-filtrate (that is, isotonic), energy-dependent reab-sorption of NaC and ClK in the ductal system resultsin a markedly hypotonic final secretion. Thisfacilitates taste. Bicarbonate allows buffering,while calcium and phosphate allow for maintenanceof tooth mineral integrity. Early work defined theeffects of flow on electrolyte composition.9,10

Interestingly, the pH and ionic composition mayalso influence the activity of organic components inthe saliva. For example, lysozyme activity isinfluenced by electrolytes and salivary anions oflow-charge density.8 Thiocyanite, the anionic pro-duct of the salivary peroxidase system, alsopotentiates lysozyme activity.11

bacterial binding sites (termed cryptipopes) hidden concentrations than the histatins. It is interesting

Saliva and health 225in the tertiary structure.15,16 As well as theseproperties, PRPs bind dietary tannins, and theirexpression in rodents is dramatically increasedby ingestion of tannins.17 This suggests an evol-utionary role in protecting the organism from thepotentially deleterious effects of a toxic substancecommonly found in the human diet.

Another protein, statherin, allows saliva tomaintain its state of supersaturation with respectto calcium and phosphate salts.18 Statherin and thePRPs provide attachment to tooth and other oralsurfaces for a variety of oral microorganisms,including Streptococcus mutans (but interestinglynot S. sobrinus), Actinomyces viscosus and Candidaalbicans species.15,16,19 Thus, these protein com-ponents contribute greatly to the maintenance ofan intact dentition through their binding andinhibition of spontaneous calcium phosphate pre-cipitation and crystal growth, while at the sametime providing possibilities for heterogeneities inmicrobial colonization through their specific bac-terial binding patterns.

Histatins are another group of proteins that havereceived much interest. These are small (35 KDa),basic, histidine-rich proteins found in both parotidand submandibular/sublingual saliva.20 Of particu-lar interest is the fact that the histatins have potentanti-candidal effects, and it has been suggestedthat these activities could be exploited as a naturaldefense against candida.21 A major breakthrough inthe application of molecular biology to treatmentof disease occurred when a recombinant adenovirusvector containing histatin-3 DNA was successfullytransferred into rat parotid glands.22 Furthermore,the expressed protein was secreted into the ratsaliva (histatins are not found in rodents) and hadbioactivity against candida.

Mucins, the major organic component of sub-mandibular/sublingual saliva, are large glyco-proteins consisting of two major groups,arbitrarily defined as MG1 (103 kDa) and MG2 (130150 kDa). Their high degree of glycosylation andpotential for hydration prevent desiccation, theirviscoelastic properties provide lubrication. Theymay also bind to toxins, agglutinate bacteria,interact with host cells, and are important com-ponents of the acquired pellicle and plaquematrix.2325 It has also been suggested that themucins protect the oesophagus in gastroesophagealreflux disease.26 Thus, reductions in the output ofmucins could have a number of effects on oral andsystemic health, as well as quality of life.

Other anti-microbial proteins of saliva includelysozyme, lactoferrin, peroxidases and sIgA,although these are present at much lowerthat, paradoxically, concentrations of both lyso-zyme and histatins are elevated with candidacarriage, implying that there is a reactive increaseto infections.27,28

In summary, there are a number of proteins andglycoproteins in human saliva that may have aninfluence on many aspects of oral health. However,whether variations in expression and concen-trations of any of these proteins has a measurableinfluence on specific oral diseases remains to beproven.29

Mastication and salivary flowEvidence from animal and human studies suggeststhat increased mastication may increase salivaryoutput, whilst reductions in the masticatory efforthave the reverse effect. For example, parotid glandatrophy and reductions in the concentrations ofproline-rich proteins in the parotid saliva followinitiation of a liquefied diet in rats,30,31 whilstparotid gland enlargement and an increase in thesalivary flow rate follow implementation of a dietwhich requires more mastication.32 In humans,reduced flow rates of stimulated parotid, andboth unstimulated and stimulated whole salivawere found after subjects started to consume aliquid diet.33,34 Modification of the diet of institu-tionalised children to be less acidogenic, lessretentive and of firmer texture resulted in a 40%increase in the flow rate of stimulated parotidsaliva, as well as an increased plaque pH.35 Weshowed that salivary flow rates were significantlycorrelated with maximal bite force.36 The flow rateof unstimulated whole saliva was significantlyincreased when human subjects chewed four sticksof sugar-free gum per day for eight weeks.37

Frequent consumption of sugar-free chewing gumfor two weeks resulted in increases in stimulatedparotid saliva flow rates and reductions in plaqueacidogenicity.38 However, EMG assessments ofmasseter muscle activity during eating and gumchewing suggest that diet alteration alone isprobably insufficient to produce the extent ofmasticatory stimulus required for a measurableincrease in salivary gland function in community-dwelling adults.39 The use of sugar-free gum toenhance remineralisation by stimulation of salivaryflow is now an accepted preventive therapy, andhas been successful in the market place as well.40

Dawes41 described a computer model of salivaryclearance that was expanded to define the effectsof some of these variables on clearance.42,43

Crucially, it was not the stimulated flow ratethat had the greatest influence on clearance, butthe unstimulated flow rate. Again, this ties into

concepts of reserve capacity. Perhaps the reason

Salivary composition and caries

phenotype with caries severity. Results have typi-

Quantitative studies relating salivary concen-trations of the predominant protein componentshave rarely been conducted. Mandel et al.62 found

M.W.J. Dodds et al.226The influence of saliva on the caries process isfundamental; in some way, saliva affects all threeof the components of Keyes classic Venn diagramof caries aetiology (that is, tooth, plaque andsubstrate). Flow rates and clearance, pH and buffercapacity, calcium phosphate homeostasis andeffects on bacterial metabolism, adsorption tooral tissues and elimination from the oral cavityare all obvious manifestations of the saliva/cariesinteraction. Many studies have attempted to relatecertain aspects of salivary output and compositionto caries susceptibility. Most of those studies lookedat either the physico-chemical properties of saliva(flow rate, buffer capacity)4650 or specific com-ponents of saliva with anti-microbial activity, suchas salivary IgA, lactoferrin, lysozyme, and thesalivary peroxidase-hypothiocyanate system.5157

With the possible exception of the hypothiocyanatesystem and IgA, the consensus is that a relationshipbetween caries experience and activity of any ofthe salivary antimicrobial proteins cannot bedemonstrated.

The PRPs of human parotid saliva exhibit geneticpolymorphisms13 that have lead to a number ofinvestigations attempting to relate their geneticwhy so few studies have been able to definitivelylink saliva flow and caries activity is that they havemeasured the wrong variable. Stimulated wholesaliva and parotid saliva have frequently been takenas the index of salivary function. However, what ifstimulated flow is within normal limits, and theunstimulated flow is affected? Sreebny describedhow the greatest contributor to total salivaryoutput during the diurnal cycle is the unstimulatedflow.44 Similarly, an individual affected by xerosto-mia may actually be noticing the discomfortassociated with a lack of unstimulated saliva bath-ing the oral tissues. Dawes reported that thesubjective symptoms of dry mouth did not occuruntil the unstimulated whole saliva flow rate hadfallen from between 40 and 50% of initial values insubjects receiving doses of anti-cholinergic drugs.45

Interestingly, the major contributor to unstimu-lated flow is the submandibular gland, whichproduces the less serous, mucin-rich saliva thatcoats the oral tissues, providing lubrication andrelief from desiccation. Parotid flow increasesdramatically during stimulation, and its main rolemay be to produce copious, highly buffered, fluid toprotect against extrinsic insult (for instance, acid).no difference in parotid saliva proteins betweencaries-resistant and caries-active adults. Balekjianet al.63 found that a caries-rampant group exhibiteda significant reduction in the proportion of basicproteins and a significant increase in amylasecompared to a caries-resistant group. Conversely,Mandel and Bennick found no differences inconcentrations of the acidic PRPs between caries-free and caries-susceptible subjects.64 While quan-titative studies of salivary composition and cariesactivity have been inconclusive, there is evidencethat similar proteins in saliva from caries-active andcaries-free individuals may have different levels ofbiological activity.6568 Our laboratory found nodifferences in parotid saliva flow rates and buffercapacity in caries active versus caries-free youngadults, although the caries-active group hadslightly, but significantly, higher parotid salivarypotassium and chloride concentrations.69 Salivaregulates the plaque pH by minimizing the pH-lowering effects of sugars,47 whereas increasing theflow of saliva by chewing wax or a sugar free gumresults in an increase in plaque pH.40,70

Many cross-sectional studies have attempted torelate salivary flow rates and/or composition andcaries. However, a fundamental flaw of any suchstudy is the use of the DMF index as a measure ofcaries activity. The DMF index is a life-timecumulative index of dental disease and treatment,and may have little bearing on caries activity at aspecific point in time. Similarly, a one-timedetermination of stimulated whole saliva flow ratedoes not pass muster as a comprehensive evaluationof salivary function. Other, more sensitive, indi-cators of caries activity need to be used, possiblycombining in vivo demineralisation/remineralisa-tion models with other indicators of caries activitytogether with repeated, standardised and compre-hensive salivary collections.

Saliva and aging

Mouth dryness (xerostomia) is a common clinicalcomplaint in the elderly.71 Numerous studies haveinvestigated the effect of aging on salivary glandcally been contradictory in terms of finding arelationship between caries prevalence (DMFS)and salivary genetic phenotype. Some studieshave shown such a relationship,58,59 while othersfound no correlation.60,61

secretion, but these effects remain unclear, asconflicting results, especially regarding wholesaliva and submandibular/sublingual salivasecretions, have been reported. While some studiesreport age-related decreases in whole and glandu-lar salivary output,7275 others show no age-relateddeclines in healthy non-medicated subjects.7678

Sreebny, in his excellent and comprehensivereview,1 published summary tables of the literatureon salivary function and aging.

Since many of the previous studies were either insmall populations, or did not measure all salivarysecretions, we undertook a study investigating

reports on salivary function and aging, this inves-tigation used a large, community-based population,with a demographic profile and health problemsrepresentative of the population at large.

With the exception of UP saliva, the flow rates forall the salivary secretions measured declined withage. Table 1 shows the age-related declines for thetotal population and for sub-populations (healthysubjects, those with diabetes, hypertension, orother, that is, those taking other medicationsassumed to affect saliva output). There was adecrease in saliva output for all of the majorsecretions, although SP flow appeared to be least

ane in

.01%

.00

ge g

Saliva and health 227effects of age, medications and certain age-associated systemic diseases (type 2 diabetesmellitus and hypertension) on salivary flow ratesand composition in a community-based cross-sectional cohort,27,79,80 described in the followingsection. A total of 1130 subjects, completed thestudy, with a mean age of 59.9 years (range: 3581years). 635 were female, and 495 male.

Saliva was collected from all major salivaryglands, and defined as follows: unstimulatedwhole (UW), unstimulated (UP) and stimulated(SP) parotid saliva, unstimulated (US) and stimu-lated (SS) submandibular/sublingual saliva. Flowrates were determined and compositional analysiswas also completed for the following variables:(1) electrolytes (Na, K, Ca, Cl); (2) total protein;and (3) individual proteins (histatins 1, 3, and 5;mucins, MG 1 and MG 2; albumin, lysozyme,lactoferrin, secretory IgA,cystatins and peroxi-dases). Details of the methods are to be found inearlier publications.7981

Results of this study indicated that there are age-associated alterations in certain aspects of salivarygland function. Specifically, flow rates of unstimu-lated whole saliva, stimulated parotid saliva, aswell as unstimulated and stimulated submandibu-lar/sublingual saliva all decreased with increasingage. These results confirm the consensus that, inthe general population, salivary secretion declineswith increasing age. Unlike many of the previous

Table 1 Age-related declines for the total populationvalue for the linear regression analysis, with the R2 valu

N UW SP

Total 1130 p!0.0001 (0.021) P!0Changea K29% K41Diabetes 233 Ns NsHypertension 227 ns NsHealthy 240 p!0.05 (0.028) NsOther 430 p!0.05 (0.013) p!0

a Percentage change of mean values for youngest vs. oldest aaffected statistically, if not numerically. With theexception of SP saliva flow rates, this decrease wasapparent for all the disease category groups, imply-ing that there is a primary effect of aging on salivaryoutput, independent of disease and/or pharmaco-logical therapy. These effects are illustrated for USsaliva, which showed the most significant age-related decline in flow rates, (Fig. 1). There werealso sex differences in flow rates as indicated inFig. 2. Females had lower flow rates than males forUW (p!0.0001; Fig. 2A) and US saliva (p!0.05;Fig. 2B). Fig. 2A shows that in healthy, non-medicated females, therewasa noticeabledecreaseinUWflowratebetween the4554and5564yearagecategories. Since this non-medicatedgroupexcludesfemales taking hormone replacement therapy(HRT), it is possible that this is indicative of a flowrate alteration coincident with menopause, pointingto hormonal effects on salivary flow rates. Fig. 2Bshowsthat forUS saliva the sexdifference tends tobenegated in the older age groups.

Table 2 indicates the age-related alterations(represented as increases ([) or decreases (Y),followed by the p value) in total protein andelectrolyte concentration and output as determinedby linear regression analysis in the whole popu-lation. It is evident that some of the concentrationeffects are flow rate-dependent (for instance, SPprotein output), but not the majority of theparameters.

d each of the sub-populations, represented by the pparentheses.

US SS

(0.009) P!0.0001 (0.048) P!0.0001 (0.069)K40% K40%p!0.05 (0.021) p!0.001 (0.053)p!0.001 (0.051) p!0.01 (0.034)p!0.01 (0.04) p!0.0001 (0.106)

1 (0.029) p!0.01 (0.021) p!0.001 (0.033)

roups.

Figure 1 Mean flow rate of US saliva (ml/min/gland) against age group for disease categories (healthy, hypertension,ean

M.W.J. Dodds et al.228Alterations with age in the concentrations ofspecific anti-microbial and other proteins in SP andSS saliva as determined by linear regression analysisin the whole population are indicated in Table 3.The decrease in concentration of both the histatins,and mucins with age may have important impli-cations with respect to both oral comfort (mucins)and resistance to candidal infection (histatins).These appear to be specific decreases, as proteinconcentrations either increase with age (SP, US) or

diabetes). Error bars indicate the standard error of the mremain stable (SS).

Figure 2 A. UW flow rates (ml/min) broken down by age cshows healthy (non-medicated sub-population. B. US flow raet al.79 with the kind permission of Editrice Kurtis SRL.One condition that has frequently been associ-ated with alterations in salivary flow and compo-sition is diabetes mellitus. Reduced salivaryflow rates in diabetic subjects were noted insome reports,82,83 but not others.84,85 In ourstudy, diabetic subjects had significant reductionsin output of both stimulated and unstimulatedsubmandibular/sublingual saliva, although notstimulated parotid or unstimulated whole saliva.80

Analysis of the protein components of saliva

.revealed significant increases in the concentrations

ategory, sex. Bars indicate whole population; line graphtes in whole population. Fig. 2A is reproduced from Yeh

Arguably the single most common side effect of

ases (K) or decreases (Y), followed by the p value) inoutput as determined by linear regression analysis in the

liva US saliva SS saliva

0.0001 [, p!0.001 no change0.0001 Y, p!0.01 Y, p!0.00010.0001 [, p!0.0001 [, p!0.00010.01 [, p!0.0001 Y, p!0.00010.0001 [, p!0.0001 [, p!0.0001

ange Y, p!0.05 Y, p!0.00010.01 Y, p!0.0001 Y, p!0.0001

ange No change Y, p!0.00010.01 Y, p!0.05 Y, p!0.0001

ange Y, p!0.01 Y, p!0.0001

Saliva and health 229of a number of proteins in the diabetic subjects,including SP lactoferrin (Fig. 3A), myeloperoxidaseand salivary peroxidase, as well as SS total protein,albumin, lactoferrin (Fig. 3B) and secretory IgA.Most notably, mean myeloperoxidase concen-trations in SP saliva showed nearly a four-foldincrease in diabetic subjects, and SP lactoferrinconcentrations were 70% higher. Lysozyme concen-trations were 26% higher, sIgA concentrations 30%higher, and salivary peroxidase concentrationsincreased 128% in diabetic versus healthy subjects.

These disease effects differed in many cases withthe age category. For example, in the younger agegroups, flow rates for subjects with either diabetesor hypertension tended to be lower than in non-medicated controls of the same age group; in theoldest age group this effect was not apparent.Conversely, lactoferrin concentrations tended to beelevated in diabetics (and to a lesser extent inhypertensives); however, this effect was negated in

Table 2 Age-related alterations (represented as incresalivary total protein and electrolyte concentration andwhole population.

N (SP/US/SS) SP sa

A. ConcentrationTotal Protein (mg/ml) 808/1111/1092 [, p!Na (mEq/L) 672/714/861 Y, p!K (mEq/L) 672/714/861 [, p!Cl (mEq/L) 808/837/1092 Y, p!Ca (mEq/L) 672/714/861 [, p!

B. OutputTotal Protein (mg/min) no chNa (mEq/min) Y, p!K (mEq/min) No chCl (mEq/min) Y, p!Ca (mEq/min) No chthe oldest age group in SS saliva (Fig. 3B), althoughnot in SP (Fig. 3A). Other alterations in lysozyme,IgA and albumin were noted in SS saliva only, mostof which were due to elevated concentrations ofthese proteins in the diabetic group.

The implication of these data is that thesediseases, or their treatment, may have a greaterrelative detrimental effect in younger than in olderindividuals. The increased lactoferrin concen-tration in diabetes could indicate either thatthere is specific induction of lactoferrin secretionby acinar and/or ductal cells, or that there is aglandular lymphocytic infiltrate associated withchronic sialadenitis.86 Although there is a signifi-cant negative correlation of SP and SS lactoferrinconcentrations with flow rates, the lactoferrinalterations in diabetics were not related to flowmany drugs is dry mouth.87,88 Although theseeffects are well known, there have been surpris-ingly few studies that have looked at objectivemeasurements of salivary flow and taking medi-cations. There is certainly evidence that, as thenumber of medications being taken by an individualincrease, there is a corresponding decrease in salivarate, at least in SP, as lactoferrin output wassignificantly higher in diabetics than non-medicatedcontrols. Further investigation of specific effects ofdiabetes on salivary protein components aresuggested by these findings as there is a strongimplication that salivary function and, thus oralhealth are compromised in diabetes.

Effects of drugs on salivary functionoutput.

Table 3 Alterations with age in the concentrations ofspecific anti-microbial and other proteins as determinedby linear regression analysis in the whole population.

Protein N (SP/SS) SP saliva SS saliva

Lactoferrin 672/953 [, p!0.01 [, p!0.0001Lysozyme 672/953 No change Y, p!0.0001SIgA 675/954 [, p!0.05 no changeAlbumin 674/954 [, p!0.05 no changeCystatin 958 nd no changeMG1 833 nd Y, p!0.0001MG2 833 nd Y, p!0.0001HRP1 80/80 no change Y, p!0.01HRP3 80/80 Y, p!0.05 Y, p!0.01HRP5 80/80 Y, p!0.01 Y, p!0.01

ndZnot determined.

patients. Unfortunately, at least part of theproblem is that, for the most part, there is not a

disciplined preventive practices to deter the nega-tive effects of reduced salivary flow.

g/m

M.W.J. Dodds et al.230Effects of radiation on salivary function

Other groups of patients with high caries activitythat may be associated with decreased salivary flowinclude patients who have received radiationtherapy for head and neck cancer. Despite theirlow rate of cell turnover, salivary acinar cells areexquisitely sensitive to radiation, and xerostomia isan early and persistent sequela of head and neckirradiation.89 Both parotid and submandibular/sublingual glands are susceptible to radiation-induced damage.90 Damage depends on the radi-ation dose and fields, but typical doses required totreat most squamous cell carcinomas of the oralcavity, oro- and naso-pharynx, tonsils and tongueare in the range of 5070 Gy in divided doses over aperiod of several weeks. It has been suggested thatto maintain parotid function radiation dosage to the

91

Figure 3 A. SP lactoferrin concentrations (mparotids should be 26 Gy or lower. This wellexceeds the threshold for damage to salivarygland tissue. It has been suggested that the earlyradiation effects on salivary output may be due tomembrane damage affecting signal transduction atthe receptor/G protein level, with later damageoccurring at downstream elements of thecascade.92

Conclusions

Clearly, saliva has profound effects on the oralcavity, but as Sreebny1 has noted, few dentalpractitioners bother to ask the necessary questionsor make the necessary observations and/ormeasurements to determine whether there is anylevel of salivary gland hypofunction in theirAcknowledgements

This work was supported by NIH DE 10756. We aregrateful to the many skilled technicians whoassisted in the sampling and analysis of the data.simple fix to a broken saliva flow. We can only hopethat future trends in molecular biology researchmay allow the xerostomic patient to regain func-tion. Until then, dentists should be more aware oftheir patients salivary function and include morel); B. SS lactoferrin concentrations (mg/ml).References

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Saliva and health 233

Health benefits of saliva: a reviewIntroductionBasic concepts of saliva secretionSalivary compositionInorganic constituents of salivaOrganic constituents of saliva

Salivary composition and cariesSaliva and agingEffects of drugs on salivary functionEffects of radiation on salivary functionConclusionsAcknowledgementsReferences