The four circles diagrammatically represent the factors involved in the carious process.all four factors must act concurrently (overlapping of the circles)for caries to occur Micro- organisms no caries no caries host & tooth Sub- strate caries no caries no caries time
Host factor: saliva What is saliva here mean? a. major saliva glands Saliva parotid, submandibular, sublingual b. minor gland c. gingival exudate
Why Saliva? • Animal experiments • Clinical observations
Animal experiment Effect of desalivation on caries in hamsters Group No. hamsters Avg. no. Avg. caries carious teeth score Intact salivary glands 20 2.3 4.0 Desalivated* 10 10.5 39.0 * Parotid, submandibular, and sublingual glands.
Clinical observations Xerostomia: decreased or lack of salivary secretion Cause: therapeutic radiation salivary glands disorder (e.g. sjogren syndrome) taking medicine
Caries in a patient with impaired salivary function as result of radiation therapy (courtesy of Drs Jansma and Vissink, RUG, the Netherlands.
The caries is different from common. Decay offer seen in cervical area, a rapid demineralization over broad surfaces with no cavity. the huge change in quantity of saliva is responsible.
In xerostomia The amount of bacteria The quality of plaque change S.mutans, Lactobacillus, Yeast, Actinomyce S. sanguis, Veillonella, Neisseria
Decayed, missing, and filled teeth prior to the anticholinergic therapy obtained from the patient’s dental records and roentgenographs
Full-mouth roentgenographs of patient showing rampant caries and pulpal involvement of mandibular anterior teeth
Decayed, missing, and filled teeth of a patient who received prolonged anticholinergic therapy for a duodenal ulcer. Note the steep caries increment (DMFT 27) that occurred during the time of xerostomia
Salivary composition and caries Relationship between salivary characteristics and caries prevalence Property Relationship Property Relationship Flow rate ± pH - Buffer capacity + Ca - PO4 - NH3 - Amylase Viscosity - Urea - + positive relation; ± some relation; - no relation.
Flushing and neutralizing effect refered as “Salivary Clearance” or “Oral Clearance Capacity”
The Dawes (1983) model of oral clearance. Saliva is produced at a rate dependent on the concentration of sugar in the saliva. When a maximum volume of saliva (Vmax) is reached, a swallow occurs and the salivary volume decreases to a residual volume (Resid), thereby eliminating some of the sugar
Flow rate of saliva Unstimulated 0.3ml/min 0.7~1.5L/day Severe xerostomia 0.05ml/min
A computer simulation of the effect of changes in the unstimulated flow rate on the clearance of sucrose after a 10% sucrose mouthrinse. The simulation assumed average values for Resid (0.8ml), and Vmax (1.1 ml)
Sucrose concentrations in saliva at different sites and times after a 10% sucrose mouthrinse WS=whole saliva; FUM=facial upper molars FUI=facial palatal upper incisors LLM=lingual lower molars FLM=facial lower molars
high flow rate high buffer capacity flow rate bicarbonate concentration Na+ Electrolyte concentration as a function of salivary flow rate. See also chapter 3
Salivary composition and caries : contradictory results, because of the difficulties in study
Relationship between salivary characteristics and caries prevalence Property Relationship Property Relationship Flow rate ± pH - Buffer capacity + Ca - PO4 - NH3 - Amylase Viscosity - Urea - + positive relation; ± some relation; - no relation.
Salivary buffers In saliva, two chief buffer system, bicarbonate-carbonic acid (HCO3-/H2CO3, PK1=6.1) AND phosphate (HPO4=/H2PO4-, PK2=6.8)
Dialysis of saliva, remove all ion, keep protein , no buffer capacity remained.
Diagram of a Stephan curve – the plaque pH response to a 10% glucose solution (Redrawn from Jenkins, The physiology and biochemistry of the mouth. Blackwell, London, 1978).
The effect of restricting the access of saliva to plaque upon the shape of the Stephan curve (Reproduced from) Jenkins, the physiology and biocbemistry of the mouth. Black well, London, 1978)
Mean Stephan curved following rinsing with sucrose alone and following parafilm chewing or cheese chewing. Reproduced from Higham and Edgar; Caries Res 1989;23:42-48
Concept of “Critical pH” In normal concentration of calcium and phosphate, the critical pH is 5.5.
Antibacterial factor of glandular origin
Lysozyme （溶菌酶） Hydrolytic enzyme, cleaves the 1-4 linkage between N-acetylglucosamine and (N-乙酰葡糖胺）, N-acetylmuramic acid (N-乙酰胞壁酸）a structure of cell wall of bacteria.
lysozyme, exist in many tissue fluid such as tear, egg, saliva etc. • Many bacteria is resistant to lysozyme by capsule and extracellular polymers. • Animal test show lysozyme alone could not prevent caries. • Lysozyme function by affecting the ecological balance between microorganism.
Salivary peroxidase system (唾液过氧化物酶系统） Salivary peroxidase Thiocyanate ion (SCN-) from salivary glands 硫氰酸盐 Hydrogen peroxide from bacteria
Peroxidase H2O+SCN- OSCN-+H2O OSCN- 硫氰酸盐中间产物，包括二氰代硫、氰亚磺酸、氰磺酸等
OSCN- inactivate various enzyme of the glycolytic pathway and therefore inhibit growth, respiration and metabolism of many bacteria.
Lactoferrin（乳铁蛋白） • Ferric iron (Fe3+) is an essential microbial nutrient • Lactoferrin binds ferric iron, make it unavailable for microbial use. • Unbound lactoferrin may also have bactericidal effect on some microorganisms such as S.mutans
Microorganism’s policy against LF • Some bacteria produce a protein (enterochelins) binding Fe++ more effectively • Some bacteria degraded LF and use the released Fe++
Amylase （淀粉酶） A calcium metalloenzyme hydrolyses the alpha 1-4 bond of starch
Amylase may help clean the teeth of carbohydrate debris. But why appear in tears, serum, brohchial (支气管）, male and female urogenital secretions? Recent discovery: amylase may specifically binds to some oral micro-organism.
Histatins （富组蛋白） A group of small histidin-rich protein. Inhibitor of candida albicans (白色念珠菌）and S.mutans. Unstimulate saliva: 2~30nmol/ml
a 43 residue protein, produced by acinar cell Statherins • Inhibit primary precipitation of calcium phosphate, entire molecule is needed. • Inhibit secondary precipitation (crystal growth). Only first six residues are needed.
Why inhibiting precipitation? In a given pH, only supersaturated saliva would prevent demineralization (脱矿) and promote remineralization (再矿化). However, supersaturated with calcium phosphate will promote crystallization of calcium phosphate salts onto tooth surface.
Proline-rich proteins (PRPs,富脯蛋白) • 3 PRPs was identified, with around 150 amino acid residues. • Inhibition of crystal growth calculus formation, remineralization and calcium phosphate precipitation the first by 30 residues at the amino-terminal part • Important constituent of acquired pellicle • Interaction with oral bacteria, modulation of adhesion of selected bacteria to tooth surface
N C The PRPs molecule is thought to bind to tooth surface via its amino-terminal segment. tooth Binding of this segment is sufficient to fulfill the primary role (inhibition of crystal growth), and leaves the carboxy-terminal region of the molecule, which has a different composition, directed to the oral cavity, and free to interact with oral bacteria.
Caries Immunology Immunological prevention of infection disease achieved vast success in this century. smallpox, poliomyelitis etc. How about dental caries?
Theoretically, antibody may control cariogenic bacteria by • inhibit colonization, surface protein（表面蛋白）, glucosyltransferase（葡糖基转移酶GTF） • Opsonize（调理）bacteria, permitting phagocytosis
Humoral and cellular factors at the plaque/ tooth interface. Saliva provides secretory IgA, which can reach plaque both at the gingiva and at occlusal fissures. Gingival exudate provides both humoral (IgG, IgM, and IgA) antibodies and cellular components (neutrophils, lymphocytes), but only to plaque in the gingival region.