Omic - Dental Caries

Front 1

Where do carious lesions form?

Back 1

begins at a dental site where the adjacent dental plaque harbors high numbers of cariogenic bacteria (eg. Strep. mutans).

Front 2

Caries development

Back 2

1) The first change in enamel is a SUBSURFACE DECALCIFICATION which is covered by a very thin layer of intact enamel.
2) Early lesion appears as a white spot or line in the enamel and is called a WHITE SPOT LESION or an ENAMEL INCIPIENCY.
3) the thin enamel layer will break or dissolve forming a CAVITATION. Left untreated the “cavity” will progress and penetrate into the enamel and eventually the dentin.

Front 3

Rate of progression to the pulp in permanent teeth

Back 3

penetration of a carious lesion to the pulp takes between 1 to 5 years, with a mean of 4 years.

Front 4

Rate of progression to the pulp In primary teeth

Back 4

penetration to the pulp takes between 6 months to 3 years, with a mean of 2.5 years. more rapid progression in primary teeth is due to the reduced thickness of enamel and dentin compared to permanent teeth

Front 5

Why is there a wide range in rate of progression?

Back 5

The wide ranges have to do with caries susceptibility of the patient,

Front 6

The etiology of dental caries (4 things that must be present)

Back 6

1) a susceptible tooth, or mouth,
2) a specific plaque microflora,
3) a cariogenic diet (frequent consumption of sucrose and other fermentable carbohydrates) and
4) simultaneous and persistent presence of the latter 3 factors for a sufficient period of TIME (usually several weeks). Elimination or management of one or more of the above factors stops the carious process.

Front 7

When are enamel caries most common?

Back 7

1) during GROWTH SPURTS, especially the teen-age years growth spurt which has the highest caries rate of any age group,
2) 4 to 6 year olds,
3) Incidence of ROOT SURFACE CARIES is progressive with age after about 55. Above this age over half of the population in the United States will experience root surface caries. From ages 20 to the 50’s, incidence of new carious lesions on intact enamel surfaces is relatively low.

Front 8

caries before the 1800s

Back 8

Mostly root surface caries and NOT enamel caries since refined sugar was not available (know this from studying skulls)

Front 9

The Trista da Cunda studies

Back 9

Trista da Cunda is an island in the mid-Atlantic which was colonized by the British in the early 1900’s. Initially, no dental enamel caries was found in the native population. After several years of British dietary influence, ie. high consumption of confectionary foods, dental caries was found to be present in half of the population.

Front 10

What was the most cariogenic regimen with In vivo animal studies

Back 10

Strep. mutans infection plus high sucrose diets; Absence or alteration of either of these factors was associated with only mild to moderate cariogenesis.

Front 11

Vipeholm Dental Caries Study

Back 11

In vivo human study that looked at effect of diet on caries; Compared diets were control group (normal diet), sugar,bread, chocolate between meals, 8 toffees between meals, and 24 toffees between meals; * After the experimental protocols were completed, all groups received the control group diet for an additional year. Microbial studies of lactobacilli were done but cariogenicity of streptococci was not yet discovered so they did not study those, and dental hygiene, which was mostly absent, was not a research variable.

Front 12

Results of Vipeholm Dental Caries Study

Back 12

1) Rate of caries from highest to lowest: 24 toffees, 8 toffees, chocolate, bread, sugar, control group.
2) detectible sugar appeared in the mouth of the 24-Toffee group 58% of the day in contrast to a value of 13% of the day in the Sugar group.
3) mean number of carious lesions/year went back to normal during sugar restriction post-study (actually less caries than control

Front 13

Conclusions of the Vipeholm Dental Caries Study (4)

Back 13

1) Retentive (sticky) sugar-foods were more cariogenic than non-retentive ones, ie. toffees were more retentive than chocolates.
2) Sugar consumption between meals was more cariogenic than that consumed only at mealtime.
3) The FREQUENCY of sugar intake/day was more important in caries initiation than the amount of sugar consumed/day. (Total daily sugar consumption was lower in the 24-toffee group than the Sugar or Bread group.)
4) Sugar-restricted diet was enough to inhibit new caries formation, even in individuals with a history of frequent dental caries, eg. the 24-toffee group.

Front 14

5 Shortcomings of the study

Back 14

The study did not divulge 1) key microbiological aspects (The role of mutans streptococci and sucrose in cariogenesis had not been discovered yet.),
2) cariogenicity of non-sweetened starch,
3) caries preventive effect of normal dental hygiene measures
4) cariogenicity of sweetened LIQUIDS consumed several times a day between meals and 5) cariogenicity of sugar type. Surose was the main sweetner used but this was not a research variable.

Front 15

Stephan curve studies

Back 15

Stephan built an antimony pH microelectrode which could be inserted into dental plaque in vivo to examine longitudinal pH variations in plaque following exposure to various dietary substrates.

Front 16

8 Findings of the Stephan curve studies

Back 16

1) At least 3 days of no oral hygiene was necessary before dental plaque produced enough acid to measure.
2) The resting pH of most plaques, when not exposed to dietary substrates for at least 2 hours, was close to neutrality.
3) Within 3 to 10 minutes after sugar exposure, the pH of plaque dropped to between 5.5 and 4.5, a level which supports dental decalcification (ie. dissolution of calcium and phosphate ions from enamel). It remained at that pH for 30 to 45 minutes, even after sugar was removed from the mouth by water rinsing. *This latter acidity resulted mainly from glycolysis of intra-cellular polysaccharide (ICP) which was formed and stored within the bacteria during the initial exposure to sugar.
4) In the final phase of the Stephan curve, called the pH RISE PERIOD, the pH gradually returned to the resting pH (despite the absence of salivary stimulation and buffers) and RECALCIFICATION of all dissolved tooth minerals occurred. Alkalogenic bacteria in the biofilm were responsible for this outcome. (Note: sugar increased the salivary flow rate with acid-neutralizing buffers during the initial pH drop, but the acid formation overcame these.)
5) People who already have caries generate more acid than those who do not when exposed to the same amount of sugar,
6) Chewing of paraffin after the subject rinsed with a sugar solution caused the pH-rise period to occur sooner compared with no paraffin chewing. This was attributed to increased buffer in saliva when the salivary flow increased.
7) SUGAR ALCOHOLS did not produce pH drops in plaque.
8) sugar substrates with concentrations between 1.0% and 50% yielded essentially similar Stephan curves. (This suggests a THRESHOLD EFFECT in plaque acidogenesis, and that foods with decreased sugar content are not necessarily less cariogenic.) 8) Exposing plaque to sugar before its return to a resting pH (eg. every 20 minutes after first exposure) caused the pH to remain at an acidic level for as the exposures continued.

Front 17

Categories of Mutans streptococci (MS) - 4

Back 17

Can be separated into diff. 1) Serotypes (ie. different ANTIBODIES were formed to each species),
2) Biotypes (ie. Categorized biochemically - enzymes for breaking down various substrates were either present or absent),
3) Genotypes,
4) Host preference

Front 18

Host preferences of MS

Back 18

Two common species of MS cause infections in monkeys only (Strep. downei and Strep. macacae), while the others infect only humans or rodents.

Front 19

Common characteristics of all MS species

Back 19

1) DIETARY SUCROSE, but not other sugars such as glucose, was required for rampant CARIES induction in MS-infected animals.
2) MS produced ENzYMES which yielded ACID from the sugar alcohols, sorbitol and mannitol whereas other oral streptococci did not.
3) Only MS streptococci formed GELATINOUS PLAQUES on wires suspended in sucrose broth.

Front 20

most important species of MS in human cariogenesis (2)

Back 20

Strep. mutans and Strep. sobrinus.

Front 21

Where does MS tend to colonize in the mouth (3)?

Back 21

1) only hard tissue or surfaces (eg. tooth or appliance); it is an early colonizer of the tooth and it occupies the deep regions of plaque adjacent to teeth,
2) Prefers supragingival “stagnation” sites, particularly dental pits and fissures (“stagnation” sites have resting pH’s below neutrality),
3) Other preferred sites are ones adjacent to either orthodontic brackets, or partial denture clasps.

Front 22

Where do humans originally get MS from?

Back 22

Infants get it from Their mother;

Front 23

Window of infectivity

Back 23

Colonization period of MS - MS transmission to infants occurs between the time of dental eruption to roughly 31 months of age.

Front 24

At what age can MS no longer be transferred to someone from another human?

Back 24

After 3 years of age; * This means that transmission from patient to dentist is unlikely, but it is possible to TRANSMIT MS FROM ONE SITE TO ANOTHER within the same mouth.

Front 25

Optimal pH for MS

Back 25

MS is SLIGHTLY aciduric and pH of 6.0 is optimal

Front 26

What concentration of MS in plaque will induce caries?

Back 26

approximately 10 to 30% of the plaque microflora

Front 27

Mixed infection

Back 27

Since MS never comprises 100% of the plaque microflora,

Front 28

What conc. of MS in SALIVA puts patient at risk for caries?

Back 28

When MS become dislodged from dental biofilms and enter the saliva, the patient is considered to be at risk for dental caries when levels exceed 105/ml of saliva. *Saliva testing is sometimes used to assess caries risk

Front 29

What streptococcal species does MS INHIBIT (2)?

Back 29

MS are antagonistic to other streptococcal species in the biofilm and can inhibit Strep. gordonii and Strep. sanguinis (formerly Strep. sanguis)

Front 30

How does MS inhibit other sterp species?

Back 30

by its acid and MUTACIN, a bacteriocin controlled by quorum sensing.

Front 31

In response, how can Strep. sanguinis inhibit MS? Strep. Gordonii?

Back 31

1) Strep. Sanguinis: Inhibits MS by its HYDROGEN PEROXIDE,
2) Strep. Gordonii: Inhibits MS via CHALLISIN, a proteolytic enzyme which destroys quorum sensing molecules of MS and thus mutacin production.

Front 32

Clonal variants of MS

Back 32

Clonal variants emerge in a longstanding sucrose environment to become more aciduric and consequently more acidogenic than wild-types of MS; These are the most virulent stains of MS.

Front 33

Why does MS fail to thrive AFTER cavitation has occurred?

Back 33

Once cavitation occurs, accessibility to saliva and buffering mechanisms diminish causing the environmental pH to decrease to a level where MS are no longer competitive.

Front 34

What bacteria dominates AFTER cavitation?

Back 34

Lactobacilli (LB), a very aciduric bacteria that can reach levels of up to 90% of the biofilm microflora in deep enamel and dentin. * MS is considered to be the initiator of the carious lesion and LB a secondary invader. Without the presence of MS most enamel cavitations will not occur.

Front 35

What can impede the progression of lesions AFTER cavitation?

Back 35

only drastic sugar restriction, fluoride exposure, salivary access and/or restoration will impede or stop progression of the lesion.

Front 36

Optimal pH for LB

Back 36

pH of close to 5.0.

Front 37

What 3 species of LB dominate in deep carious lesions (dentinal lesions)?

Back 37

1) L. casei, 2) L. fermentum and 3) L. rhamnosus

Front 38

Characteristics of LB (oxygen requirements and metabolism, reproduction)

Back 38

Most LB are facultative and saccharolytic, producing mainly lactic acid as a by-product; However, LB are NOT AS ACIDOGENIC AS MS and MULTIPLY MORE SLOWLY

Front 39

Where else does LB colonize in the mouth?

Back 39

soft tissue, particularly the tongue, and can achieve high levels in the mouth

Front 40

What kind of sugar causes LB to multiply?

Back 40

ANY TYPE OF SUGAR, not just sucrose

Front 41

When are salivary levels of LB the highest?

Back 41

1) when unrestored dentinal lesions are present, 2) in association with orthodontic or other appliances, 3) in patients with severe caries (eg. xerostomic patients)

Front 42

Best treatments for MS? (3)

Back 42

FLUORIDE or antimicrobial agents CHLORHEXIDINE or XYLITOL

Front 43

Treating LB

Back 43

Not as susceptible to the treatments that work with MS; Best controlled by reducing dietary sugars and levels of MS

Front 44

Mechanisms of Attachment and proliferation in MS

Back 44

1)Attach via adhesins, 2) Sucrose allows for creating extra-cellular polysaccharide (ECP) after attachment, which enhances proliferation in biofilm

Front 45

Sucrose

Back 45

DISSACHARIDE OF glucose + fructose

Front 46

ECP formation

Back 46

1) MS (and other oral streptococci) possess constitutive enzymes (always present and do not have to be induced) on its cell surface called GLUCOSYL-TRANSFERASES (GT; also called glycosyl-transferases) which bind to sucrose , 2) GT splits the disaccharide bond of sucrose to liberate fructose and glusoce, 3) GT adds the glucose molecule to the end of a polymer of glucose units called a GLUCAN, 3) This polysaccharide is an ECP which is attached to GT and hence to the bacterial cell. *The liberated fructose molecule becomes free to be metabolized as an energy source by this organism or other bacteria in the biofilm.

Front 47

Glucan formed by MS

Back 47

called MUTAN; unique because insoluble in water and can be degraded only by MS enzymes so it can act as a protective barrier; Also increases plaque volume, which discourages penetration by salivary buffers *Mutan itself does not directly harm dental surfaces

Front 48

Molecular structure of mutan

Back 48

Contains alpha 1 to 3 linkages (the #1 carbon atom of a glucose molecule is attached to the #3 carbon of the adjacent glucose molecule);

Front 49

The glucan formed by most other oral streptococci

Back 49

called DEXTRAN, which is water soluble and can be metabolized for energy by many biofilm residents

Front 50

Molecular structure of dextran

Back 50

Contains alpha 1 to 6 linkages;

Front 51

Glucan binding site (GBS)

Back 51

protein adhesins in MS attached to the cell wall that bind to any type of glucan and do not have enzymatic functions. This method of linking progeny of MS (daughter cells) or other MS cells in the area to the tooth-bound MS colonizers allows a MICROCOLONY to form; * The concentrated and localized nature of the MS microcolony enhances acid from sucrose metabolism onto the dental surface

Front 52

Non-bacterial plaque

Back 52

GT enzymes may become dislodged from cell walls by mechanical forces and can bind to other oral surfaces like pellicle where they will retain their ability to synthesize glucans from sucrose on their own. This phenomenon will result in BACTERIA-FREE GLUCAN PLAQUE that can act to increase plaque volume

Front 53

starch and glycogen

Back 53

Glucans found in nature containing mainly alpha 1 to 4 linkages; WATER SOLUBLE

Front 54

cellulose

Back 54

Glucan found in nature containing a beta 1 to 4 linkage; WATER INSOLUBLE

Front 55

The most acidogenic species in the mouth

Back 55

MS

Front 56

What mechanisms does glycolysis trigger in MS?

Back 56

cellular mechanisms to make them more aciduric and acidogenic and multiply faster

Front 57

Sucrose consumption and lactic acid formation in caries-active sites vs non-active

Back 57

In caries-active sites, higher MS and LB population are found and these plaques show higher rates of sucrose consumption and lactic acid formation.