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2002-14-2-99-104

2002-14-2-99-104

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Published by Meetika Pahuja

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Published by: Meetika Pahuja on Jun 15, 2012
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01/31/2013

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Introduction
S
aliva can be described as an essential biologicaloral fluid known for its importance in combattingthe different microbial diseases that might affectthe oral cavity such as dental caries andinflammatory mucosal diseases. Manconstituents of saliva have proven and potentially protective roles in local immune and non-immunedefense mechanisms. The antimicrobial ability has been the focus of many studies thatinvestigated the different antimicrobial factors inhealth and disease. Studies are also continuously carried out to investigate the natural defensefactors of the body so as to utilize them either inpreventionortreatment.Salivaryfactorswhichhavebeenproventoplaa significant protective role against caries includethebicarbonateandcarbondioxidebuffersystem,andcalciumandphosphateions. Togetherthesehelp to resist dental dissolution and encourageremineralisation. Othersalivarycomponentshaveantibacterialpropertieswhichincludetheabilitytoaggregate bacteria and so prevent the
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 Variations of some salivary antimicrobial factors in differentdisease states: A review 
Najla S. Dar-Odeh*, BDS, FDS, RCS (Ed) and Mohammad Awni Al-Kayed, BDS, PhD
 The antimicrobial properties of saliva had been recognized for a long time owing to their importance in the natural defensemechanismofthebody,particularlyindiseasesthathavelocaleffectsonthetissuesoftheoralcavity. Theimmuneandnon-immuneantimicrobial salivary factors have been measured in different disease states to observe the variations in their levels in an attempt tounderstand the pathogenesis of some systemic diseases and to formulate better lines of treatment particularly for diseases that areeitherdifficulttocureorthatarenottreatableyet.Theaimofthispaperwastoreviewtheliteratureonsomeantimicrobialfactorsandtheir variations in some disease states and to understand the inter-relationship between the salivary antimicrobial factors andsystemicdisseasesasffectingtheoralcavity.Inordertohaveabetterunderstandingofthefactorsaffectingsalivarysecretions,therehas to be a more standardized approach for saliva collection and analysis, more so because of some differences between thecompositionofmixedsalivaandthatfromtheindividualsalivaryglands.
colonization of mucosal and tooth surfaces. Inthe vast majority of individuals wounds of the oralmucosa caused by direct mechanical trauma healrapidly. This is in part due to the excellent bloodsupply to the mucosa, the antibacterial propertiesofsalivaandthepresenceinsalivaoffactorswhichappear to promote wound healing, possibly by speeding coagulation and possibly also by stimulatingneuralandepithelialcellgrowth. This paper will review some antimicrobialproteins of saliva which were consideredsignificant in the antimicrobial process and wereinvestigated by many scientists either to know their mechanism of action or to find out the effectof disease on such factors. It will also discuss thedisturbances that might affect these factors inconjunctionwithrelevantsystemicdiseases. There are few diseases that were noted not tobe associated with changes in the level of salivary IgA.
123,5
Review Immunefactors(IgA)
Received 11 April 2001; Revised 24 September 2001; Accepted18November2001*Assistant Professor, Department of Oral Medicine, OralSurgeryandPeriodontics;and Associate Professor, Department of Conservative Dentistry and Prosthodontics, Faculty of Dentistry, University of Jordan, Amman,Jordan
 Addressreprintrequeststo:Dr.NajlaDar-OdehSportcity P.O.Box961315 Amman11196 Jordan
Saudi Dental Journal, Vol. 14, No. 2, May - August 2002
99
 
In a number of diseases, the level of salivary IgA was reduced. Sudh investigated agroup of 25 Crohn's patients. IgA of unstimulatedsaliva was determined by ELISA technique. Although the difference in the level of salivary IgAbetween patient's group and control group wasnot statistically significant, 3 patients hadundetectablesIgA.It was also found that children prone torecurrent respiratory infections have lower levelsof salivary IgA. Saliva from lymphoma patientsreceiving chemotherapy showed decreasedconcentrations of IgA, however other salivary defensive factors showed no significantdecreases. Lymphoma patients who are oncytostatic drugs had total salivary IgA decreasedduring cancer therapy, which returned to thebaseline level after termination of treatment.Significantly lower levels of IgA were found inresting saliva of children with chronic protein-energy malnutrition. Also in thalassaemia majoranalysis of the parotid saliva showed that theconcentrationofIgAwassignificantlylower. Theparotid IgA was found to be significantly reducedin HIV-infected patients contributing to therecurrent oral infections that these patientsfrequently acquire. Challacombe and Sweethave also found that whole and parotid salivacontainedlowerIgAconcentrationinHIVandAIDSpatients. However an earlier study done b Atkinson found that the saliva of HIV-positive patients contained increased levels of lgAinstimulatedsubmandibularsaliva. A study conducted by Schiodt revealedthat HIV patients with salivary gland disease hadsignificantdecreaseinthelevelofsalivaryprotein,and increase in salivary IgA. Insulin- dependentdiabetes was shown by Tenovuo to beassociated with higher levels of salivary IgA thanhealthy patients. Samplesconsisted of stimulated whole saliva which were collected from 35 insulin-dependent diabetic patients. Non-insulindependent diabetics were also shown to haveincreased levels of salivary IgA. Chronicleukemic patients also had increased level of salivary IgA. Patients with primary Sjogren'ssyndromeshowedhigherconcentrationsofIgA,in whole and parotid saliva reflecting the localinflammatoryactivityofthesalivaryglands. Fordobserved a positive trend in theconcentration of total protein and salivary IgAfollowing the administration of radioactive iodineused for the treatment of hyperthyroidism.Patients undergoing open heart surgery alsoshowed increased salivary secretion of IgA. In
et al.et al.et al.et al.et al.
4467891011 1212131414151617181920
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one variant of amyloidosis, the concentrations of salivaryIgAwereobservedtobehigherinpatientsthaninnormalsubjects.1. This salivary enzyme was found to beunaffected by some systemic diseases.Lysozymewasshowntobereducedinanumberof diseases. Patientsundergoingopenheartsurgery showedadecreaseinthesalivarysecretionofnon-immune host defense factors includinglysozyme. Pinducciu found that insulin-dependent diabetes mellitus (type one) wasassociated with significantly decreased salivary lysozyme concentration. Other diseasesassociated with a significant decrease in lysozymeconcentration include HIV infection associated with salivary gland disease. In thalassaemiamajor analysis of the parotid saliva showed thatalthough the concentration of lysozyme waslower, the difference was statistically notsignificant. Meurman investigated agroup of 22 patients treated for Hodgkin's diseaseand non-Hodgkin's lymphoma by chemotherapy.Lysozyme of stimulated saliva was assessed with amodifiacation of the lysoplate method. Theobserved that saliva had decreasedconcentrationsoflysozyme. Anearlierstudydoneby the same author found that lymphoma patients who are on cytostatic drugs had significantincreases in albumin secretion and lysozymeconcentrationofsaliva.Mandel found that salivary lysozyme was increased in HIV patients and that it increasedin concentration with time. The saliva of HIVpositive patients was also found to containincreased levels of lysozyme in stimulatedsubmandibular saliva. Patients with chronicleukemia exhibited normal lysozyme content of saliva which was elevated in those patients withsevere periodontal disease. In one variant of amyloidosis, the concentrations of salivary lysozyme, were higher in patients than in normalsubjects.2.Normal values of salivary lactoferrin werenoticed in a number of diseases. Otherdiseases were associated with reduced levels of salivary lactoferrin. Lactoferrin output was shownto be significantly reduced in HIV-positiveindividuals. However, when examining thestimulatedsubmandibularsaliva,Atkinson
Non-immunefactors
LysozymeLactoferrin
3-4,2420 221410 782313173-4,24,261113
et al.et al.et al.et al.
DAR-ODEH AND KAYED
Saudi Dental Journal, Vol. 14, No. 2, May - August 2002
 
101
foundthatsalivaofHIVpositivepatientscontainedincreased levels of lactoferrin. A study conductedby Schiodt revealed that HIV patients withsalivary gland disease had significantly reducedsalivary lactoferrin levels contributing to therecurrent oral infections that these patientsfrequently acquire. Significantly lower levels of lactoferrin, were found in resting saliva of children with chronic protein-energy malnutrition. Non-insulin dependent diabetics were shown to haveincreased levels of lactoferrin. Lactoferrincontent was also increased in parotid saliva of irradiatedpatients.3. This enzyme was found to be reduced inconcentration in certain diseases like the case of lymphoma patients receiving chemotherapy.However, Laine . found that lymphomapatients who are on cytostatic drugs had nochange in total protein and amylaseconcentrations by chemotherapy. Patientsundergoing open heart surgery have also showeda decrease in the salivary secretion of non-immune host defense factors including amylase.In one variant of amyloidosis, the concentrationsof salivary amylase were higher in patients than innormalsubjects.4.Lal . found that Histatins weredecreasing in AIDS patients. However, Atkinson. (1990) found that the saliva of HIV-positivepatients contained increased levels of histatins instimulatedsubmandibularsaliva.5.Normal values of salivary peroxidase werefound in a few diseases. Lundgren .found that total protein is high while peroxidaselower in patients with Papillon-lefèvre syndrome. The patients' group consisted of 16 patients withthe syndrome. Salivary peroxidase in stimulatedsaliva was determined using the method of Gothefors and Marlund. Patients undergoingopen heart surgery also showed a decrease in thesalivary secretion of non-immune host defensefactorsincludingperoxidase.In insulin-dependent diabetics the only non-immune factor of saliva that is altered(increased in concentration) is peroxidase. Non-insulin dependent diabetics also had increasedlevels of salivary peroxidase. Mandel .found that salivary peroxidase was increased in
7
et al.et al et aet al et al et al 
149162520821294,24 3201516 21
 AmylaseHistatinsPeroxidaseHIV patients and that it increased in concentration with time. In one variant of amyloidosis, theconcentrations of peroxidase were higher inpatientsthaninnormalsubjects. This review of literature aims at realizing theassociation of important systemic diseases withsalivary antimicrobial proteins. In order to be ableto study the association of a certain disease withsalivary composition, a relatively large number of patients has to be included in the study. This isessential to overcome the individual variations insalivarycomposition.Itisalsoofprimeimportanceto standardize all the other variables that areknown to affect the composition of saliva.However,thisisextremelydifficulttoachieve. Thecomposition of saliva varies according to thesalivary flow rate. For example, as the flow rateincreases, the concentration of proteins rises.Resting saliva is the ideal state to study saliva as itis the predominant state for most of the day.However, it does not yield the required amount of salivarysamples. Another important issue that faces theinvestigator is whether the salivary sample mixed(whole) or collected from a particular salivary gland. This is important since the source of salivamay well affect its composition. Intake of foodand the circadian rhythmic variations in theconcentration of many salivary constituents aretwo more factors governing the composition of saliva. Considering that salivary collectionproblems are overcome, there is still one essentialfactor to be considered. Salivary samples have tobe treated and analyzed with caution as many salivary constituents are liable to decomposition if notstoredandtreatedintheappropriateway. The salivary antimicrobial property may bepotentiated by the synergistic action exhibited by some of them. It was shown that salivary antimicrobial proteins may interact in a commonsystemtoinfluencetheoralecology. Thisnaturaldefense system may be influenced by the varioussystemic diseases. It was shown that systemicdiseases can induce changes in the salivary composition.It can be observed that the changes that affectsaliva composition in the different diseasesdepend partially on the severity of the diseaseprocessandwhetheritaffectstheimmunesystemof the body. These changes may also beinfluenced by whether the salivary glands areaffected or not. In certain diseases they are
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Discussion
SALIVARY ANTIMICROBIAL FACTORS
Saudi Dental Journal, Vol. 14, No. 2, May - August 2002

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