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Etiology of Dental Caries 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 Microorganisms no caries host & tooth no caries Substrate 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 Clinical observation 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 A case report 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 Flow rate ± Buffer capacity + Property Relationship pH Ca PO4 NH3 Amylase Viscosity Urea + positive relation; ± some relation; - no relation. - - Why flow rate? 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 Flow rate ± Buffer capacity + Property Relationship pH 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) Bicarbonate is most important buffer system 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 Nacetylglucosamine and (N乙酰葡糖胺）, Nacetylmuramic 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-) 硫氰酸盐 from salivary glands 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 Statherins （富酪蛋白） Statherins a 43 residue protein, produced by acinar cell 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 The PRPs molecule is thought to bind to tooth surface via its aminoterminal segment. N C 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. Electron micrograph of a human dimeric IgA myeloma protein Polypeptide chain structure of human IgA Structure of human secretory IgA1 (sIgA1) Animal studies Animial caries model rodent or primates Diet containing sucrose (diet 2000) Infected test cariogenic bacteria Control group Caries development is determined by Keyes method 取唾液 本课题获国家自然科学 基金重点项目资助 取静脉血 Candidate antigen Whole cell Whole protein or peptide Part of peptide, one more dormain Cheramic peptide -- AgI/II~GTF DNA vaccin Active immunization SIgA, locally or via gut serum antibody, via systematic Passive immunization Passive immunization Monoclonal antibody against S.mutans Monoclonal antibody against the surface protein antigen of S.sobrinus (Pag) 4 3.5 3 2.5 血清抗PAc -IgG 血清抗PAc-IgA 唾液抗PAc-IgG 唾液抗PAc-IgA 2 1.5 1 0.5 0 A B C D E 各实验组大鼠血清及唾液中特异性抗体水平分析（OD405） A 重组质粒pCIA-P C 重组质粒pCIA-P E 生理盐水 B 重组质粒pCIA-P D 空载体制裁粒pCI 80 70 60 50 E级龋损 Ds级龋损 Dm级龋损 40 30 20 10 0 A B C D E 各实验组大鼠磨牙龋齿计分分析 5 4 Series 1 Series 2 Series 3 Series 4 Series 5 Series 6 Series 7 Series 8 Series 9 Series 10 3 2 1 0 A B C 茸毛链球菌占总的可培养细菌的百分数 C. PBS处理组 A 单抗处理组 B 腹水对照组 C PBS处理组 S.sobrinus S.mutans S.rattus Immunoelectron microscopy of PcAb against S.sobrinus 6715 whole cells reacted with the three bacteria S.sobrinus S.mutans Immunoeletorn microscopy of McAb ZS2/286 reacted with the three bacteria S.rattus Immunoeletorn microscopy of non-specific mice ascites reacted with S.sobrinus 6715 Polyclonal antibody against a S.mutans GTase-I overexpression strain Polyclonal antibody against caries in milk IgY against caries in hen egg-yolk Western blot of overexpress GTase-I strain Effect of specific bovine milk antibodies against dental caries construction of GTase-I overexpressing strain B29-33 intramuscular immunization specific cow milk antibodies mouse rinsing colonization level of S.mutan on teeth surface immunization milk collection ¡ý¡ý¡ý¡ý ¡ý¡ý ¡ý¡ý¡ý¡ý¡ý¡ý¡ý¡ý¡ý¡ý¡ý Scheme of cow immunization OD(405nm) 0.4 0.3 Two cows both immunized with the GTase over-expression strain developed good IgG in milk. 0.2 0.1 Series 1 0 3 25 50 60 75 days after parturition Specific IgG level in bovine milk by ELISA 95 OD405 0.5 0.4 0.3 0.2 0.1 0 4 30 62.5 temperature（℃） The effects of temperature on IgG in milk 100 Effect of specific IgY on prevention of dental caries killed S.mutans, S.sobrinus whole cells intramuscular immunization egg yolk IgY effect of specific IgY on S.mutans in vitro effect of specific IgY on caries prevention in animal models Host factors: tooth Tooth morphology and arch form Clinical Observation Pit and fissure area of posterior teeth are highly susceptible to caries. Food debris and microoganisms readily impact in the fissures. In same tooth, differences in surfaces regarding to susceptible to caries In mandibular first molars occlusal > buccal > mesial > distal > lingual In maxillary first molar occlusal > mesial > lingual (palatal) > distal > buccal Reason: Partly due to tooth morphology pit and fissure > smooth few caries in cuspal area In first molar, distal area is free to saliva for 4-5 year, whereas the mesia area readily form dental plaque in 4~5 day after eruption. Defect in tooth Plaque growth 24 hours after cleaning, on a central maxillary incisor of a patient who is an “abundant” plaque former. Note the spread along the gingival margin, the crack, and other surface defects. Extensive dental caries on the left side of maxilla and mandible in a patient who has received > 40 Gy radiation dose to the area of the left parotid gland Where dental plaque likely to form? Stagnation area (滞留区） Photograph of plaque accumulation in stagnation areas after omission of toothbrushing for 3 days. Note that accumulations preferentially occur along the gingival margin and interproximal spaces whereas no plaque accumulates in cuspal and incisal areas due to continuous mechanical wear on these areas Irregularities in arch form, crowding and over lapping of the teeth also favor the development of carious lesions. Because of more stagnation areas Clinical features immediately after removal of orthodontic appliances and cleaning. The orthodontic treatrment had lasted for 2 years. Noe the marked gingival reaction and the characteristic chalky surface appearance of the active enamel lesion. After 3 months with careful oral hygiene the gingival tissues have recovered and the active lesion has been completely arrested. The white appearance of the lesion has diminished markedly due to polishing away of the eroded outermost enamel surface Tooth composition Enamal surface is more caries-resistant than the subsurface Microradiograph of white spot lesionof enamel. Compare the extensive demineralization of the subsurface enamel with the better mineralized surface layer (original magnificaiton 100) The surface enamel has more mineral and organic matter but relatively less water. In addition, certain elements, including fluoride, chloride, zincaccumulate in the enamel surface. A-C Concentration gradients of different elements in enamel from the surface towards the enamel-dentinal junction Changes of the enamel, such as a decrease in density and permeability and a increase in nitrogen and fluoride content occur with age. This “maturation” maker the tooth more resistant to caries. Fluoride concentrations in surface enamel of deciduous canines as a function of dental caries prevalence in the deciduous dentition at the age of 6 years. No straightforward relationship to illustrate that a high fluoride concentration should be linked to a low caries prevalence is seen. However, when the caries experience is high, the fluoride concentration in enamel becomes high as well. Substrate: Diet and Caries Diet: food and drink taken by any person from day to day. Function: locally systemic Locally: react with the enamel surface and by serving as a substrate for cariogenic microoganisms. Systemically: Nutrition, on melabolic processes Difficulties in identify diet role in influencing caries Reason: difficulties in control diet for a long time information only from diet history Many researches indicate the sucrose in the “arch criminal” in the etiology of caries. Cumulative dental decay prevalence, expressed as DMF permanent teeth, in children ages 11 to 12. Corresponding annual 1959 per capita sucrose utilization data for 18 countries and the state of Hawaii, from the food and Agriculture Organization of the United ations. (Courtesy of Dr. T. Marthaler.) Relationship between dental caries and mean sugar intake (g/day) for South African males (16 to 17 years old) of four different ethnic groups. There is a direct relationship between percent population caries-free and sugar intake. (Drawn from the data of Retief et al.) Interventional human studies Vipeholm study Hopewood House study Plot of the mean number of DMF teeth per child versus chronological age in state schools of Australia and in children of Hopewood House (with standard error of means). Note the extremely low caries increment of the institutionalized children while under strict dietary control and the steep increase in caries experience when dietary supervision was no longer in effect – at above 13 years of age. (Courtesy of T. Marthaler) Special population groups hereditary fructose intolerance (HFI) Assessment of cariogenic potential of foodsuffs In vitro model of caries adhesiveness of food enamel demineralization production of titratable acid Monitoring of plaque pH changes acidogenicity is measured Animal testing Adhesiveness of foods adhesiveness: attacment between food and the tooth surface, sticky food Determining sucrose content Plaque-pH curves following the application of A: lactose, glucose, maltose, fructore and sucrose, and B: raw starch, cooked starch, maltose and sucrose. Telemetrically recorded pH of interdental plaque (5 days old) in a subject during and 17 min after rinsing with 15ml of 10 per cent test solutions of Lycasin, xylitol, sorbitol, sorbose and sucrose. PC=3min paraffin chewing; U=2 min urea rinse. Other dietary components and caries Phosphates cariostatic activity animal experiment support that adding phosphate in diet reduce caries in animal, by local effect. Human study: not convincing Reason: difference in animal and human and in experiment. Trace elements Relationship of mineral elements to caries Frequency of eating and caries Vipeholm study Results of the Vipeholm dental caries study. Sugar in various forms was given either between or with meals over several years, and the rate of caries increase was studied. The caries increment was much lower wen sugar was given with meals compared with sugar between meals. (courtesy of B.E. Gustafsson.) The effect of between – meal eating on caries activity in 5- to 6-yearold children. The more snacks children eat, the higher is the caries increment. (def) Decayed, extracted, filled (teeth). (Courtesy of Weiss and Trithart.) Animal studies Early theories of caries etiology Worms: 虫牙学说 Humors体液学说: ancient greek; four fluid of body are not in balance Vital theory (活体学说) 18 century, disease originate tooth itself. Chemieal theory (化学酸学说) parmly (1819) suggest acid may induce caries. Parasitic or septic theory (寄生腐败学说) microorganism may play role, by microscope, many bacteria on tooth were found. proteolysis-chelation theory First organic matter dissolved, degraded, then, the end product may have chelating effect and thereby dissolve the minerals in the enamel. This process may happen at neutral or alkaline pH Miller chemico-parasitic theory acid was present in caries many food mixed with salive and incubate at 37℃ could decalcify tooth Several oral bacteria could produce acid to cause caries Different bacteria invade caries lesion Current concepts of caries etiology Microorganisms no caries host & tooth no caries Substrate caries no caries no caries time Clinical classification of caries Rate of caries progression 1950’s study: it took one year the enamel fissure caries develop into dentine. 1989’s study: only 50% fissure developed into dentine within 2 years. Fluoride application may retard caries progression The progression rates of proximal caries lesions from initial enamel caries to dentinal caries in permanent dentition was estimate to 68 (2 years at age 7, 4 years at age 12). Classification according to progression rate Acute caries: progress fast, often in children and teenagers, light colored cavity. Rampant caries, many tooth involved at same time acute caries feature often accompanied by systematic disorder. Such as sjogren syndrome or saliva reduction after radiation. Caries in a patient with impaired salivary function as result of radiation therapy (courtesy of Drs Jansma and Vissink, RUG, the Netherlands). Chronic caries progress slowly, black or brown colored cavity hard remaining dentine Arrested caries caries stop progressing because of the local etiological change Secondary caries (recurrent caries) caries recurred after treatment. Often at the margin the filling materials restoration or beneath The shadow located on the mesiolingual cusp adjacent to the larger occlusal amalgam restoration on the maxillary right first molar indicates the presence of carious dentin Classification according to the involving site Occlusal caries Root caries Smooth surface caries Classification according to the deepness Superfacial caries(浅龋) white spot lesions, visibly frosted surface brown spot Dentin caries (中龋) cavitated lesion involving the up part of dentin Deep caries (深龋) cavitated lesion involving the pupal third of dentin Diagnosis • Visual change •Probing: rough surface or trapping point pain upon probing • Temperature test • X-ray examination • Transillumination Visual change Matte, white, active cervical lesions Probing: rough surface or trapping point pain upon probing The explorer tip can easily damage white spot lesions Temperature test X-ray examination transillumination Proximal caries lesion is detected in an anterior tooth with the use of transillumination Superfacial caries(浅龋) White spot or brown, dark lesion, rough upon probing No complaint, no hyper sensitivity Dentin caries (中龋) Cavity, hypersensitivity upon probing, hot or cold stimulus. Deep caries (深龋) Deep cavity, very sensitive and some pain upon stimulus, however the pain disappear as soon as the stimulus is taken away.