Animal Models in PR

7/25/2019 Animal Models in PR

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ANIMAL MODELSIN

PERIODONTOLOGY


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INTRODUCTION

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The concept of animal models

!AT IS AN ANIMAL"

Et#molo$icall#% the &o'd (animal) de'i*es f'om theLatin animal meanin$ so+l,spi'it% th+s desc'i-in$li*in$ o'$anisms that a'e animated.

!AT IS A MODEL"

A model is an o-/ect of imitation% somethin$ thatacc+'atel# 'esem-les somethin$ else% a pe'son o'thin$ that is the li0eness o' ima$e of anothe'

An animal model is an animated object ofimitation, an image of Man (or other species),

used to investigate a physio- or pathologicalcircumstance in question

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Types of vertebrate tooth attachment1

2i-'o+s attachment Sharks

Teeth are attached at their base with mass of irregularcalcied tissue where bers from brous layer of jawcontinues in jaw.

An0#losis- sh reptiles.

!alcied union between teeth and bone.

!in$ed attachment "oby sh pike

#ncalcied brous hinge between tooth and bone.

Gomphosis $t is the only form of tooth attachment present in mammals.

%asticatory forces are transferred to bone with help ofsuspensory function of periodontal ligament.

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T#pes

E3plo'ato'#

aimin$ to +nde'stand a -iolo$ical mechanism% &hethe'is a mechanism ope'ati*e in f+ndamentall# no'mal-iolo$# o' a mechanism associated &ith an a-no'mal

-iolo$ical f+nction

E3planato'#

models aimin$ to +nde'stand a mo'e o' less comple3-iolo$ical p'o-lem

P'edicti*e

These models a'e +sed &ith the aim of disco*e'in$ and4+antif#in$ the impact of a t'eatment% &hethe' this isto c+'e a disease o' to assess to3icit# of a chemical

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!omolo$o+s

if the s#mptoms sho&n -# the animal and the co+'se ofthe condition a'e identical to those of h+mans

Isomo'phic

if the animal s#mptoms a'e simila' -+t the ca+se of thes#mptoms di5e's -et&een h+man and model

Pa'tial These models do not mimic the enti'e h+man disease

-+t ma# -e +sed to st+d# ce'tain aspects o' t'eatmentsof the h+man disease.

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T#pes


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Classi6cation of disease models

7. Ind+ced 8e3pe'imental9 disease models !ealth# animals in &hich the condition to -e

in*esti$ated is e3pe'imentall# ind+ced

:. Spontaneo+s 8$enetic9 disease models

Use the nat+'all# occ+''in$ $enetic *a'iants;. T'ans$enic disease models

Gene -ased


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Rationale fo' +sin$ animal modelin Pe'iodontics

&nimal models for testing periodontal regenerativeprocedures are necessary because controlled 'uantitativehistological analysis is re'uired to evaluate the 'uality ande(tent of newly formed supporting tissues. These studies are

not possible in man because of the need to retrieve teeth andsurrounding periodontium in large blocks appropriate forhistological analysis.

)roper evaluation of a new therapy necessarily involves the

use of treated and untreated controls which are di*icult toobtain in the human.

The testing of potentially harmful new devices and drugs maybe unethical in man prior to thorough evaluation in higher

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Choice of the -est animalmodel,'e4+i'ements

App'op'iateness as an analo$ T'ansfe'a-ilit# of info'mation

Genetic +nifo'mit# of o'$anisms% &he'e applica-le Bac0$'o+nd 0no&led$e of -iolo$ical p'ope'ties Cost and a*aila-ilit# Gene'alia-ilit# of the 'es+lts Ease of and adapta-ilit# to e3pe'imental

manip+lation Ecolo$ical conse4+ences Ethical implications !o+sin$ a*aila-ilit# Sie of animal N+m-e's needed Life span Se3 Amo+nt of data needed A$e of animal P'o$en# needed

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2o' S+'$ical Techni4+es

anatomic feat+'es s+ch as sie *a'iations.

St+dies of Pe'iodontal Disease% Etiolo$#% o+nd healin$ o'The'ape+tic 'esponses

M+st foc+s +pon the anatomic and -iolo$ic% 'elatedness toh+mans.

A$e The a$e of #o+n$ animals ma# -e dete'mined -# tooth

e'+ption% se3+al mat+'ation o' -one de*elopment in hand@&'ist 'adio$'aphs.

Yo+n$ ad+lts ma# -e p'efe'a-le fo' ce'tain st+dies -eca+sethe# do not displa# the se*e'e att'ition o-se'*ed in olde'animals.

It sho+ld -e noted that the a$e at &hich pe'manent toothe'+ption -e$ins and is completes *a'ies $'eatl# -et&een

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@The sie of the dentition of h+mans and di5e'ent non@h+man p'imates de*iates d'amaticall#

Cynomolgus monkey,

Macaca fascicularis

Squirrel monkey,

Saimiri sciureus


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Ch i f th - t i l


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Special e3amination methods

Di'ect o-se'*ation

Ma$ni6ed photo$'aphs

Ma$nif#in$ $lass

Ste'eomic'oscope

Radio$'aphs

!istomet'ic methods ena-le meas+'ement of thedimensions of /+nctional and poc0et epitheli+m%connecti*e tiss+e attachment le*el and al*eola' -onele*el

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e3pe'iments

B# compa'ison &ith h+man s+-/ects% animal models ha*e se*e'alad*anta$es

Constant en*i'onmental conditions can -e maintained o*e' lon$pe'iods of time% $'eatl# inc'easin$ the po&e' to detect $enetice5ects

Di5e'ent en*i'onmental conditions can -e imposed se4+entiall#on indi*id+als to cha'acte'ie $enot#pe@en*i'onmentinte'actions

Comple3 pedi$'ees that a'e m+ch mo'e po&e'f+l fo' $eneticanal#sis than t#picall# a*aila-le h+man pedi$'ees can -e$ene'ated

Genetic h#potheses can -e tested p'ospecti*el# -# selecti*ematin$s

Essential in*asi*e and te'minal e3pe'iments can -e cond+cted

An o-*io+s ad*anta$e of e3pe'imentation in animal s#stems isthe possi-ilit# of c'eatin$ pai'ed defects of e4+al sie% &hichsimpli6es statistical handlin$ of data

Limitations of animal e3pe'iments

Not all h+man diseases can -e 'ep'od+ced in animals. 1


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The Gnoto-iotic animal

P+'e s#stems of -iolo$ical mechanism

8i9 it po't'a#s the host eithe' &hen f'ee f'om $e'ms and left to its

o&n 'eso+'ces o' &hen modi6ed -# 0no&n mic'o-ial o' othe'associates%

8ii9 it pe'mits the st+d# of inte'o'a 'elationships &ithin the hosto'$anism.

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De6nitions

INBRED STRAINAn in-'ed st'ain is one that has -een

maintained -# si-lin$ 8siste' 3 -'othe'9 matin$s fo'

: o' mo'e consec+ti*e $ene'ations.


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Animals As Models

Small and ine3pensi*e'odents

Mice

Rats

!amste's

Min0s

La'$e' animals

Do$s Sheep.

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Non@h+man p'imates

Ba-oon

Maca4+e Chimpanee

Go'illa

Fa'io+s othe' species incl+de

Apes.

Cats.

!o'ses.

G+inea pi$s.

!ed$e ho$s. Pi$s.

Lem+'s.

Mon$ooses.

+S+'icates.+ol*es.+2o3es.+Racoons.+Ra--its.

+Coatis.+2e''et.+The Mon$olian $e'-il.+The least sh'e&+Cattle.

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RODENTS

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Mice

O+t of man# st'ains pop+latin$ the nat+'al ha-itat% onl#t&o st'ains of the dee' mo+se. 8Pe'om#sc+smanic+lat+sand Pe'om#sc+s o'eas9 ha*e -een e3amined and st+died-'ie#.

The pe'iodontal tiss+es of the contin+o+sl# $'o&in$

inciso's a'e 'a'el# a5ected -# pe'iodontitis. Onl# the mola'tiss+es a'e commonl# a5ected

In-'ed st'ains that att'acted attention &e'e RAP al-ino

The C> BR , dcHN The C>L , !eN The C>BL , HN DBA , :HN

STR , N SR , N

BL , !eNThe hilJte S&iss e-ste'AKR@le+0emic

C2 le+0emic and non@le+0emicThe sho't li*ed s&issal-inoBN=The G'e# lethalThe poc0et mo+se

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Mice as &ell as othe' 'odents p'esent comple3 se'iesof ph#siolo$ical alte'ations in*ol*in$ the mola' 'e$ion

C'o&n &ea's o+t


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Bae' and Be'nic0 87>9


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In Mice S+- lethal doses of 3@'a# i''adiation 8+pto > 'ad9

Tooth De*elopment

Rampant pe'iodontitis &ith tooth loss

These lon$e' c'ate'@li0e poc0ets e3tendin$ to the apices of theteeth &e'e pac0ed &ith -acte'ial deposits attached in pa't of the'oot s+'face.

The spontaneo+s fo'ms of le+0emia occ+' in se*e'al st'ains of hi$hl#in-'ed mice% -+t not at all animals ha*e -een p'edisposed to

pe'iodontitis.

G'e# lethal mo+se% is a m+tation of the ho+se mo+se% ca''#in$ a sin$le'ecessi*e $ene C% it seems to ha*e $enetic s+scepti-ilit# to pe'iodontaldisease

One can hardly escape the conclusion that basic physiological phenomena such

as continuous growth and tooth eruption, occlusal wear, cementum deposition,and the resulting changes in tooth position are of varying magnitude in the

dierent strains of mice, and that these phenomena have been in part mistakenfor evidence of periodontal disease.

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Most e3tensi*el# st+died than in an# othe' 'odents Tho+$h in pa'tic+la' dental and pe'iodontal st'ains di5e' in

sie.. P'inciples of tiss+e st'+ct+'e and $'o&th phenomena a'eidentical in all st'ains

Most f'e4+entl# +sed in-'ed


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The White lobund

Wistr lbino !ts

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Simila'ities

St'+ct+'e of the dento@$in$i*al a'ea in the 'at%

Incl+din$ the /+nctional epitheli+m and itsattachment to the tooth s+'face%

The con6$+'ation and topo$'aph# of theepithelial tiss+es at the $in$i*al ma'$in and

The *e'# shallo& $in$i*al s+lc+s &ith the f'ee

s+'face of the /+nctional epitheli+m at its-ottom o' at the le*el of the $in$i*al ma'$in

Di5e'ence Onl# si$ni6cant di5e'ence is c'e*ic+la'

epitheli+m% in 'ats is 0e'atinied.

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S"rgue#$ley rt

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Pe'iodontitis in 'ats is a -acte'ial disease% st'on$l# inte'fe'es&ith ph#siolo$ical $'o&th phenomenon'es+ltin$ in local c'ate'in$% $ene'alied de$'adation of theal*eola' p'ocess in the a-sence of a ch'onic imm+nopatholo$icin6lt'ate

inc'easin$ the pe'centa$e of s+c'ose added to a 6nel# po&de'eddiet accele'ates the 'ate of disease p'o$'ession.

A$e dependent $'o&th phenomena Se'ies of 6nel# t+ned and inte''elated tiss+e chan$es..

G'o&th of the /a&sea' of occl+sal s+'faces Contin+o+s e'+ption of teethApposition of cement+m and -one.

Some o-se'*ations !ei$ht of anatomic c'o&n


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"ingivitis in pla'ue susceptible rats showed that pla'uecollected from pla'ue susceptible rat was very much similarto human dental pla'ue.8A+mo7>9.

List$a'ten 87>9observed epithelial relationship in thegingiva of rat.

,ral pithelium in rats is well keratinied and containsnumerous keratohyalin granules

!ells of ,ral Sulcular pithelium are connected to /unctionalpithelium by intercellular junctional in spite of di*erence of0eratiniation

The attachment of the /unctional pithelium to both toothand connective tissue was mediated by basal lamina and

hemidesmosomes

1ong-term e*ect of systemic tetracycline administration onthe severity of induced periodontitis in the rat showed thattetracycline treated animals demonstrated signicantly less

resorption alveolar bone. 2eine'7>9 1


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!amste's

St'ain most commonl# +sed fo' pe'iodontal'esea'ch


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!amste's 0ept on a coa'se con*entional diet &itho+t hi$hca'-oh#d'ates% de*elop pe'iodontal lesions spontaneo+sl#.These di5e' f'om lesions seen in hamste's cons+min$ hi$h@ca'-oh#d'ate diets in &hich the# ha*e a di5e'ent fo'ms andocc+' late'. Lesions a'e spo'adic and appea' p'efe'entiall# in

the ma3illa'# 'e$ion -+t not p'io' to the a$e of a-o+t months. Actinom#ces *isco+s is p'ominent -acte'ia in diseased

hamste's. The diet dependant pe'iodontal s#nd'ome in the hamste' &as

'eco$nied as a potential candidate fo' +se as an e3pe'imentalanimal.

Anti-iotics s+ch as penicillin G% A+'eom#cin% Spi'am#cin andFancom#cin p'e*ent pla4+e fo'mation in !amste's

Pe'iodontal disease in the hamste' 'esem-les in t#pe% feat+'esand patho$enicit# *e'# m+ch &hat has -een o-se'*ed in the 'at

Dia-etic Chinese hamste' has simila'it# to h+man dia-etics. The condition in the Chinese hamste' &as p'ima'il#

panc'eo$enic. The -eta cells e3hi-it de$'an+lations0a'#ol#sis

Thic0enin$ of -asement mem-'ane of small -lood *essels

and dela#ed healin$ &as seen1


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Min0s

Cha'acte'istic dental feat+'es of min0 incl+de the p'esenceof diastema distal to the ma3illa'# thi'd inciso's% &hichaccommodate the mandi-+la' canines &hen the /a&s a'eclosed% and +n+s+all# la'$e ma3illa'# thi'd p'emola's andmandi-+la' 6'st mola's

B'oad spect'+m of pe'iodontal alte'ation


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DOGS

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Do$ is an e3cellent e3pe'imental animal to st+d#

$in$i*al and pe'iodontal disease

Relati*el# small% eas# to handle and e3t'emel#coope'ati*e d+'in$ e3pe'imentation

O'al tiss+e especiall# the $in$i*al@dental /+nction% thepe'iodonti+m% and the sie of thei' teeth a'e 4+itesimila' to those of h+mans

ell cha'acte'ied species is the Bea$le% -+tmon$'els% Ge'man pointe's a'e also +sed.

Pe'iodontitis occ+'s spontaneo+sl# -oth in do$s -'edand 0ept in la'$e colonies


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DOGS

Pe'manent teeth of the do$ consists of ;

inciso's% 7 canine% = p'emola's and ; mola's inthe mandi-le and : mola's in the ma3illa8Na*ia 79.

In *ie& of thei' docile tempe'ament andnat+'al s+scepti-ilit# to pe'iodontal disease%do$s% pa'tic+la'l# -ea$les% a'e +sed in dental'esea'ch fo' the st+d# of pe'iodontal disease

p'o$'ession% $+ided tiss+e 'e$ene'ation% tiss+e&o+nd healin$% and dental implants.

Do$s maintained pla4+e f'ee -# 'epeatedscalin$s and metic+lo+s pla4+e cont'ol cande*elop clinicall# health# $in$i*a.

Dental 2o'm+la I 7,;% C 7,7% M ;,; and I ;,;% C 7,7% Pm =,= M :,:9.

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The etiolo$ic facto's of pe'iodontal diseaseseem to -e identical in h+mans and do$s8Attst'm et al. 7>% E'icsson et al. 7>% Gad79

Do$s ma# the'efo'e -e of *al+e as a model fo'

e3pe'imental $in$i*itis.

The fact that it is possi-le to maintainpe'iodontal health in sites &he'e pla4+eacc+m+lation &as p'e*ented con6'ms simila''epo'ts in h+mans 8Lindhe N#man 7>%Theilade Attst'Qm 7>9

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O'i$inall#% it &as 'epo'ted that pe'iodontaldisease -e$an slo&l# in #o+n$ do$s andinc'eased &ith a$e 8Gad 79% p'o$'essin$a-o+t >3 faste' in do$s than h+mans 8E'icsson

et al. 7>9.

Late'% it &as doc+mented that the 'an$e andse*e'it# of $in$i*itis and pe'iodontitis *a'ied in-oth #o+n$ and olde' do$s and that $in$i*itis in#o+n$e' do$s did not necessa'il# p'o$'ess intope'iodontitis 8!+ll 7=9.

Gin$i*al 'ecession is an o+tstandin$ feat+'e in

do$s &ith pe'iodontitis 8E'icsson et al. 7>9. 1

DOGS


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DOGS

Di5e'ences e3ist -et&een do$ and man in thelocation of the inammato'# in6lt'ate in ea'l#$in$i*itis.

In the do$% the initial in6lt'ate located in thema'$inal pa't of the $in$i*a% p'oceeds alon$ the/+nctional epitheli+m lea*in$ the connecti*e tiss+ein a 'elati*el# no'mal state.

In health# do$s 0ept pla4+e f'ee fo' p'olon$ed

pe'iods of time% a $in$i*al s+lc+s is not e*ident% -+ta poc0et de*elops &ith the onset of $in$i*itis8Lindhe R#lande' 7>9.

Gin$i*itis did not necessa'il# p'o$'ess intope'iodontitis and a *a'iet# of facto's ma# in+ence

this con*e'sion 8Lindhe et al. 7>9. 1


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DOGS

It has -een demonst'ated that ind+ced $in$i*itis in #o+n$-ea$le do$s can p'o$'ess into pe'iodontitis% simpl# -# allo&in$additional pla4+e to acc+m+late 8Soames Da*ies 79.

This p'ocess can -e accele'ated -# the placement of li$at+'es

8Lindhe E'icsson 79.

!istolo$ic feat+'es a'e cha'acte'istic of an ad*anced lesion%&ith the ma/o'it# of tiss+e dest'+ction occ+''in$ &ithin the 7st= &ee0s follo&in$ li$at+'e placement 8Sch'oede' Lindhe7>9.

Class II and III f+'cations ma# -e fo+nd in the -ea$le do$. i0es/ et al. 87=9 &as a-le to c'eate the same li$at+'e@

ind+ced int'a-on# defects demonst'ated in mon0e#s -# Catonet al. 7% 7=.

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Do$s

This &as done -# s+'$icall# 'emo*in$ al*eola' -onea'o+nd the ci'c+mfe'ence of mandi-+la' p'emola'si0es/ et al. 7=.

The s+'$icall# c'eated -on# defect in the do$ isdi5e'ent than that of a nat+'all#@occ+''in$ -on#defect.

Fa'iations in attachment loss -et&een ad/acent

s+'faces ma0e it di5ic+lt to doc+ment thep'es+'$ical sie of the defect and to e*al+ate theposts+'$ical healin$ 'esponse 8Sel*i$% 7=9.

A m+ch faste' -one t+'no*e' 'ate% and a di5e'enta'chitect+'e and thic0ness of -one limit thes+ita-ilit# of do$s fo' 'e$ene'ati*e st+dies

8Gianno-ile et al. 7=9. 1


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Do$s

Ea'l# implant 'esea'ch +tilied do$s% as &ell as 'ats%hamste'% $+inea pi$s% 'a--its and cats to e3plo'e thepathoph#siolo$# of tiss+e in/+'# and 'epai'.

Osseointe$'ation &as demonst'ated in *a'io+s pa'tsof the animal s0eleton &hen titani+m 63t+'es &e'e

placed B'anema'0 7;.

E*en tho+$h do$s ha*e -een +sed most f'e4+entl#d+e to thei' sie and the simple mo'pholo$# of the'oots% the'e a'e di5e'ences in the distances of the

ante'io' and poste'io' teeth 'elati*e to the point ofmandi-+la' a'tic+lation.

2+'the'mo'e% eatin$ mo*ements consistin$ of -itin$and $'aspin$ pla#s di5e'ent f+nctional demands onthe -one 8Na*ia 79.

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Do$s

Altho+$h the feat+'es of $in$i*itis and pe'iodontitis lesionsin do$s closel# 'esem-le those in h+mans% the'e a'e stilldi5e'ences.

Inammato'# lesions in do$s -e$in in the most co'onal

po'tion of the connecti*e tiss+e at the $in$i*al ma'$in% 'athe'than late'al and apical to the -ase of the $in$i*al s+lc+s as inh+mans.

ith inc'easin$ se*e'it# of $in$i*itis% the enti'e thic0ness ofthe ma'$inal $in$i*a is in*ol*ed and not /+st the tiss+e late'al

to the $in$i*al poc0et &all 8Matsson Attst'm 79.

Limitationsof the +se of a canine model incl+des $'eat inte'@animal *a'ia-ilit#% e3pense% limited n+m-e' of -on# defectsa*aila-le and faste' -one fo'mation 8Gianno-ile et al. 7=9.

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The patte'n and p'o$'ession of ch'onic pe'iodontitis in

the colon# do$s o-se'*ed -# Pa$e and Sch'oede' 8779

&as ma'0edl# di5e'ent f'om that seen in domesticdo$s. In the colon# do$s% the thi'd and fo+'th

p'emola's and than the 6'st mola's a'e late and onl#

pa'tiall# in*ol*ed. Se*e'e -one 'eso'ption appea's

soone' and mo'e se*e'el# in the -if+'cation 'e$ionsthan inte'dental 'e$ions the 6'st and second p'emola's

a'e the teeth most f'e4+entl# lost. In the sample of

domestic do$s pe'iodontitis &as st'ictl# localied%

+np'edicta-l# a5ectin$ sin$le 'oots of eithe' f'ontteeth o' p'emola's and e*en of the second mola's.

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Ca5esse 879studied the e*ects of guided tissue

regeneration 2"T34 in the treatment of class $$ furcation

defects in beagle dogs. Si( female beagle dogs with

naturally occurring periodontitis were treated with "T3 on

test side. Teeth receiving only surgery acted as controls.

"ore-Te( material was removed one month following

surgery. &ll dogs were sacriced at 5 months. %esio-distal

sections were evaluated by descriptive histology. The

results showed the application of "T3 principles improved

the modality of wound healing of class $$ furcation defects.

6ew cementum connective tissue and alveolar bone

regeneration were predominant in the test sites.

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Bone healing around implants placed in a jawdefect augmented with Bio-Oss in dogs.

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2ERRETS

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Not as st+died as p'e*io+s species.

2i'st desc'i-ed -# Kin$ et. al in 7>=

S+ita-le models fo' st+d#in$ calc+l+s

St'+ct+'e..simila' !#d'o3#apatite

Main di5e'ence .. Less mine'alied

Diet in+enced -+t not as m+ch as m+ch in 'ats

Pe'iodontal p'o$'ession is simila' to h+mans


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S!EEP

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La'$el# domestic animals and -'ed in la'$e n+m-e's

Some st+died st'ains


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Spontaneo+s Pe'iodontitis

: t#pes

A5ectin$ the inciso's

7 P'emat+'e loss.. Sheddin$ of pe'manentinciso's.. E3cessi*e st'ess on inciso's ""

7 Red+ction in -ite d+e to mola' att'ition alsos+$$ested..

7 Othe' facto's.. Genetics< infection f'om

pa'tic+la' -acte'iaA5ectin$ the inciso's and the mola's

Some 6ndin$s in sheep a'e as follo&s..

P'emat. Loss of tooth associated &ith pe'iodontitis

A-no'mal e'+ption and e3cessi*e &ea' of pe'm inciso's

2'e4+ent p'esence of denti$e'o+s c#sts

Ant mand 'adio$'aphs


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NON@!UMAN PRIMATES

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In desi$nin$ an# medical o' dental animal st+d#% it is oftenad*anta$eo+s to select an animal that is ph#lo$eneticall# simila'to h+mans.

The &ide 'an$e of non@h+man p'imate species allo&s

app'op'iate selection fo' di5e'ent in*esti$ations. Each species has +ni4+e simila'ities and dissimila'ities to

h+mans.

Non@h+man p'imates ha*e simila' o'al st'+ct+'es to h+mans andha*e nat+'all# occ+''in$ dental pla4+e% calc+l+s and $in$i*itis%-+t small inc'ease in poc0et depths.

The ma/o'it# of non@h+man p'imates ha*e simila' decid+o+s andpe'manent dental fo'm+las as man &ith closel# 'elated dentalanatom#% altho+$h the sie of teeth a'e d'amaticall# smalle'.

The o'$aniation of colla$en 6-e's in $in$i*al and pe'iodontalconnecti*e tiss+e a'e also simila' to that of h+mans. 1

NON@!UMAN PRIMATES


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The st'+ct+'e and feat+'es of the dental andpe'iodontal tiss+es of non@h+man p'imates closel#'esem-le those of man

All species a'e diph#odont.

Maca4+es ha*e dental fo'm+la

8I :,:% C 7,7% Pm :,:% M ;,;9%

hile ma'mosets ha*e

8I :,:% C 7,7% Pm ;,;% M :,:9.

1


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Clinicall#% health# mon0e# $in$i*a is histolo$icall#indistin$+isha-le f'om h+man $in$i*a.

A shift in the composition of pla4+e o'a f'om an ea'l#$in$i*itis to a late' sta$e is also compa'a-le to h+mans8K'#$ie' et al. 7;%Scho+ et al. 7;9.

The inammato'# in6lt'ate associated &ith pe'iodontaldisease is mic'oscopicall# simila' to h+mans in somespecies s+ch as the c#nomol$+s mon0e#s (Macaca

fascicularis), -+t the s4+i''el mon0e#s (Saimirisciureus) and ma'mosets ha*e limited n+m-e's of

l#mphoc#tes and plasma cells% ma0in$ theminapp'op'iate models fo' st+d#in$ patho$enesis ofpe'iodontitis. 8Sho+ et al. 7;% B'ec3 et al. 7>%Ko'nman et al. 77a%List$a'ten Elle$aa'd 7;%Pa$e Sch'oede' 7:% Pa$e et al. 7:9.

1

NON@!UMAN PRIMATES


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It &as fo+nd that the incidence and de$'ee of an$+la'defects &as not a5ected -# the p'esence o' a-sence oft'a+matic in/+'# 8Polson 7=9.

Mon0e#s ha*e -een +sed &idel# as an animal model fo'

st+d#in$ pe'iodontal s+'$ical p'oced+'es.

Smalle' non@h+man p'imates s+ch as ma'mosets ha*esmall o'al ca*ities &hich ma# p'ecl+de thei' +se fo'ce'tain pe'iodontal p'oced+'es.

La'$e non@h+man p'imates ha*e a nat+'all# occ+''in$pe'iodontitis% -+t it occ+'s late' in life and the lesions a'eas#mmet'ical 8Caton et al. 7=9.

The'efo'e% if osseo+s lesions a'e needed fo' clinicalst+dies% the# a'e +s+all# e3pe'imentall# ind+ced.

1

NON@!UMAN PRIMATES


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Simila' dental anatom#% pe'iodontal &o+nd healin$8Caton Ko&als0i 79% s+ita-ilit# of f+'cationsites 8Gianno-le et al. 7=9 and e3pe'imentall#ind+ced defects that do not spontaneo+sl#'e$ene'ate% ma0e mat+'e ad+lt c#nomol$+s and

'hes+s 8Macaca mulatta9 species $ood models fo'st+d#in$ li$at+'e@ind+ced pe'iodontitis.

Pe'iodontal lesions in these animals a'e alsos+ita-le fo' e*al+atin$ pe'iodontal 'e$ene'ati*ep'oced+'es 8Sho+ et al.7;9% especiall# sincehistomet'ic anal#sis needed to 4+antif# theamo+nt of ne& cement+m% pe'iodontal li$amentand al*eola' -one fo'med as the 'es+lt of'e$ene'ati*e pe'iodontal s+'$e'# 8Caton et al.7=9% can onl# -e done &ith animals% +s+all#mon0e#s o' do$s. 1

NON@!UMAN PRIMATES


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In the o'i$inal non@h+man p'imate modeldesc'i-ed -# Caton Ko&als0i 879%e3pe'imentall#@ind+ced pe'iodontal disease &asc'eated &ith elastic li$at+'es that &e'e 'emo*edafte' ;1 months.

The'eafte'% Caton et al.87=9 desc'i-ed ; t#pesof e3pe'imentall#@ind+ced pe'iodontal lesions.

The ac+te defect model 'e4+i'ed s+'$ical'emo*al of -one% cement+m and pe'iodontalli$ament to c'eate the defect &he'e spontaneo+s'e$ene'ation of the defects occ+'s.

The ch'onic defect model% 'e4+i'ed theplacement of o'thodontic elastics a'o+nd theci'c+mfe'ence of teeth to c'eate defects &hichma# ta0e +p to months to p'od+ce% &ith deepdefects fo+nd mo'e li0el# in p'o3imal sites than

on the facial and lin$+al s+'faces.

NON@!UMAN PRIMATES

1

NON !UMAN PRIMATES


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The ac+te,ch'onic defect model also c'eatesdefects s+'$icall#. These defects ente' ach'onic inammato'# state -# placement ofstainless steel -ands into the defects andpla4+e 'etenti*e li$at+'es.

D+e to the possi-ilit# of o-tainin$ -loc0-iopsies% the 'hes+s mon0e#% c#nomol$+smon0e#% and -a-oons ha*e -een +sed to st+d#osseointe$'ated o'al implants.

A st+d# 82'it et al.79 s+$$ested thatli$at+'e@ind+ced pe'iodontitis a'o+nd teethand li$at+'e@ind+ced pe'i@implantitis follo&simila' dest'+cti*e patte'ns% namel# alte'ation

of mic'o-iolo$ical o'a.

NON@!UMAN PRIMATES

1


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Altho+$h *a'io+s species of non@h+man p'imatesa'e ade4+ate fo' st+d#in$ di5e'ent aspects ofpe'iodontal diseases% mon0e#s a'e e3pensi*e top+'chase and maintain and a'e fe'ocio+s.

ild capt+'ed mon0e#s can -e disease ca''ie's.

Mycobacterium tuberculosis.Herpes SimplexType B, Shigella species and Simian B *i'+s a'einfectio+s to man 8Sho+ et al. 7;9.

Mon0e#s a'e also p'one to s#stemic infectionsand diseases% and pose di5ic+lties in cont'ollin$post@s+'$ical infections and t'a+ma.

NON@!UMAN PRIMATES

1

Gala$o sene$alensis -'attic+s


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G'ant et al 87;9 st+died the -+sh -a-#% ap'osimian 'esidin$ Cent'al and East Af'ica.A -'eedin$ pai' and its o5sp'in$ &e'e +sed.

B# 7= months of a$e $in$i*al inammation&as appa'ent. In some specimens f'om

animals : #ea's old the /+nctionalepitheli+m &as located on the 'oot s+'face%some t'ansseptal 6-e's had -een dest'o#ed%and -one 'eso'ption &as appa'ent.

In one #ea' old animal% an a-scess &asnoted &itho+t the f+'cation 'e$ion of onemola'. Cemental 'eso'ption and 'epositionoften 'es+lted in an0#losis of the teeth tothe -one.

1



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1

Macaca :


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Macaca : Hohnson and his co@&o'0e's ha*e assessed the nat+'e

of the inammato'# cell in6lt'ate in connecti*etiss+es at *a'io+s sta$es of spontaneo+sl#de*elopin$ $in$i*itis in M.fascic+la'is as &ell as inanimals &hose teeth &e'e cleaned and chlo'he3idineapplied fo' ; &ee0s and then left to acc+m+latepla4+e.

The composition of the inammato'# in6lt'ate in the$in$i*al tiss+es of #o+n$ M.fascic+la'is allo&ed toacc+m+late pla4+e &as assessed in a *a'iet# of+n'elated specimens 8Hohnson and !opps% 7>9.

Biops# specimens &e'e ha'*ested at *a'io+s timesfo' +pto :=; da#s afte' the -e$innin$ of pla4+eacc+m+lation and f'om olde' animals allo&ed tocollect pla4+e fo' ; #ea's.

1

Macaca :


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The clinical and histopatholo$ic feat+'es ofpla4+e ind+ced $in$i*itis in M.m+latta &e'est+died -# List$a'ten and Elle$aa'd 87;9.

In the animals on the tooth cleanin$ 'e$imen%

inammato'# cells contin+ed to -e p'esent inmost of the -iops# specimens% altho+$h thei'n+m-e's +ct+ated.

Le+0oc#tes in the a'ea of the in6lt'ate and

ne+t'ophils in the /+nctional epitheli+m -othinc'ease in n+m-e'.

In addition to l#mphoid cells and ne+t'ophils%mac'opha$es% mast cells and la'$e clea' cellsconside'ed to -e sic0 6-'o-lasts &e'e o-se'*ed.

Macaca :

1

Maccaca


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Maccaca

1


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Maccaca-Skulls

1


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Marmosets :

Gin$i*itis and pe'iodontitis ha*e -eenst+died e3tensi*el# in &ild ca+$ht andcolon# maintained ma'mosets.

Gene'all#% cotton tops 8s.Oedip+s9 and

cotton ea's 8C.Hacch+s9 ha*e -een +sed. Ea'l# 'epo'ts indicated that ma'mosets do$et ch'onic pe'iodontitis.

That the p'e*alence is hi$h and that thelesions closel# 'esem-le those seen in

h+mans. Mo'e e3tensi*e st+dies &e'e late' done on

&ild ca+$ht and colon# maintained animals8Pa$e et al% 77% 7: Le*# 779.

1

Marmossets


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Marmossets

71

Baoons :


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Baoons :

!odosh et al 8779 assessed the pe'iodontalstat+s of = Af'ican -a-oons% P. an+-is andThe'opithec+s $elada% app'o3imatel# @7 #ea'sold.

Clinical manifestations of $in$i*itis &e'eo-se'*ed in ;; of the = animals% and in ;%

pe'iodontal poc0ets &e'e fo+nd -+t &itho+t'adio$'aphic e*idence fo' -one loss. Gin$i*itis is cha'acte'ied -# the p'esence of

s+-$in$i*al pla4+e and calc+l+s and apicaldisplacement and p'olife'ation of the /+nctionalepitheli+m -+t &itho+t +lce'ation of the

epitheli+m o' s+pp+'ation. A dense inammato'# in6lt'ate consistin$ mostl#

of plasma cells and l#mphoc#tes is located in theconnecti*e tiss+es late'al to the poc0et.

1

B


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The most o-*io+s clinical feat+'e &as soft tiss+eh#pe'plasia.

The $in$i*al inde3 and o'al h#$iene inde3 sco'es a'e4+ite hi$h.

The /+nctional epitheli+m is con*e'ted to poc0etepitheli+m &hich is -# ne+t'ophils and l#mphoc#tes%incl+din$ T -lasts.

Pe'iodontal disease in the -a-oon is th+s st'i0in$l#simila' to the disease in h+mans% -oth clinicall# andmic'oscopicall#.

Baoons :

1

Baoons


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1

!himpan"ees :


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!himpan"ees : Gin$i*itis closel# 'esem-led that seen in

h+mans% &ith ne+t'ophils p'esent in the/+nctional epitheli+m and the $in$i*al *essels%alon$ &ith an in6lt'ate comp'isin$ mostl#plasma cells and l#mphoc#tes 8A'nold andBa'am% 7;9.

Patholo$icall# alte'ed 6'-'o-lasts &e'ep'esent &ithin the in6lt'ated connecti*etiss+e. In an animal of #ea's of a$e% se*e'epe'iodontitis 'es+ltin$ in tooth e3foliation andcon6ned to the 6'st mola's and inciso's &aso-se'*ed 8Pa$e et al 7>9.

The disease in this animal appea'ed to -e aco+nte'pa't of /+*enile pe'iodontitis inh+mans. 1


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CHIMP!"##S

1

#on-$uman %rimates &sed in Studies of %eriodontal


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#on $uman %rimates &sed in Studies of %eriodontalDisease %athogenesis:

2o' ethical 'easons% initiation and p'o$'essionof pe'iodontal disease as &ell as ce'tain t#pesof pe'iodontal t'eatment cannot -e st+died inh+mans.

The ina-ilit# to e3amine initiation andp'o$'ession of pe'iodontal disease and toassess ce'tain the'apies in h+mans has led to a$'eat inte'est in the +se of animal models inpe'iodontal 'esea'ch.

Some of the most p'ominent animals +sed a'enon@h+man p'imates in pe'iodontal health% inthe t'ansition f'om health to $in$i*itis tope'iodontitis% and in e3pe'imental $in$i*itisand pe'iodontitis. 1

h i-l th lt f th


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he'e possi-le% the 'es+lts of thesest+dies a'e compa'ed &ith 'es+lts f'omh+man st+dies.

Onl# a fe& st+dies ha*e compa'ed indetail the anatom#% ph#siolo$#%imm+nolo$#% and tiss+e inte'actions inmon0e#s &ith those of h+mans.

ith the e3ceptions of di5e'ences and*a'iations in sie of the dentition% then+m-e' of each tooth t#pe as &ell asla'$e' canines% p'esence of diastemata

-et&een ante'io' teeth% and an ed$e@to@ed$e 'elationship of the inciso's% thedental and pe'iodontal anatom# of non@h+man p'imates seem 4+ite simila' tothat of h+mans. 1


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GENERAL C!ARACTERISTICS

1


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So+'ces of Animal S+-/ects

Most < &ild .. Capt+'ed in thei' nat+'al ha-itats

P'o-lems fo' in*esti$ato'


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The hi$h incidence of latent and s+-clinical diseasesMa'-+'$ disease% t+-e'c+losis% 'a-ies% and

Salmonella,Shi$ella infections

necessitates specialied handlin$ p'oced+'es fo' s+chanimals.

Some *i'+ses% s+ch as Simian B *i'+s%

@ fatal &hen t'ansmitted to h+mans.

@Ens+'e that in*esti$ations do not incl+de sic0 p'imates

-Sc'eenin$ fo' disease and maintenance in 4+a'antine

@Anti@infecti*e the'ap#


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Th'eat to E3istence

A$'ic+lt+'e

Th'eatened

2+t+'e


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1

-.Conside'ations fo' SpeciesS l ti


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Selection

The ta3onomic o'de' (p'imate) is e3t'emel#

hete'o$eneo+s. Some species a'e te''est'ial somea'-o'eal.

Some a'e p'edominantl# he'-i*o'o+s% &he'easothe's a'e p'edominantl# ca'ni*o'o+s.

Acco'din$ to &ei$ht% sie of dentition% n+m-e' o'each tooth t#pe% and food% the cha'acte'istics'an$e f'om *e'# simila' to h+man to *astl#di5e'ent.

It is the'efo'e of $'eat impo'tance of select ananimal species that is app'op'iate fo' the speci6cst+d#.

The choice of species fo' 'esea'ch sho+ld -e$+ided -# a n+m-e' of facto's a*aila-lela-o'ato'# facilities% p'esence of a -'eedin$colon#% cost% ease of handlin$% and ease of ho+sin$.

1

-.Conside'ations fo' SpeciesS l ti


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2+'the'mo'e% 'elatedness to h+mans andlimitations imposed -# the sie of o'alst'+ct+'es% as &ell as the a*aila-ilit# ofapp'op'iatel#@sied pe'iodontalinst'+ments% m+st -e conside'ed.

Selection of species fo' in*esti$ations ofs+'$ical techni4+es ma# p'ima'il#conside' anatomic facto's s+ch as sie%

&he'eas st+dies of pe'iodontal diseaseetiolo$#% &o+nd healin$% o' the'ape+tic'esponse m+st foc+s +pon the anatomicand -iolo$ic 'elatedness to h+mans.

Selection

1

-.Conside'ations fo' Species


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A$e is anothe' impo'tant facto' #o+n$ ad+ltsma# -e p'efe'a-le fo' ce'tain st+dies -eca+sethe# do not displa# the se*e'e att'ition o-se'*edin olde' animals.

The a$e of #o+n$ animals ma# -e dete'mined -#tooth e'+ption% se3+al mat+'ation% o' -onede*elopment in hand@&'ist 'adio$'aphs.

It sho+ld -e noted that the a$e at &hich

pe'manent tooth e'+ption -e$ins and iscompleted% *a'ies $'eatl# -et&een species.

!o&e*e'% the'e a'e c+''entl# no 'elia-le meansfo' dete'minin$ the a$e of ad+lt% se3+all# mat+'e

&ild@capt+'ed p'imates.

-.Conside'ations fo' SpeciesSelection

1

'ges of %ermanent (ooth )ruption in #on-


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Species

Firstpermanent

tooth eruption

Lastpermanent

tooth eruption

Cynomolgus monkey(Macaca fascicularis) 18 80

Baboon (apio anubis) !! to !" ""

Cotto#ear marmoset(Callithri$ %acchus) ! to & 11 to 1'

'ges of %ermanent (ooth )ruption in #on-$uman %rimates *'ge in months+

1



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The small o'al ca*ities of se*e'al non@h+manp'imates necessitate selection of speciale3amination methods.

Di'ect o-se'*ation of ma'$inal inammationhas -een pe'fo'med in s4+i''el mon0e#s% -+t inma'mosets% ma$ni6ed photo$'aphs% ma$nif#in$$lass% o' ste'eomic'oscop# m+st -e +sed.

Radio$'aphs ha*e 'o+tinel# -een +sed in

maca4+e species and s4+i''el mon0e#s% -+tc+stom 6lm pac0s ma# -e necessa'# in thema3illa of the maca4+e species d+e the atpalatal *a+lt and the# a'e a necessit# in -oththe ma3illa and mandi-le of *e'# smallp'imates li0e s4+i''el mon0e#s.

-.Conside'ations fo' SpeciesSelection

1



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As an alte'nati*e to clinical and'adiolo$ical methods% histomet'icmethods ena-le meas+'ement of thedimensions of /+nctional and poc0et

epitheli+m% connecti*e tiss+e attachmentle*el% and al*eola' -one le*el and a'eespeciall# +sef+l fo' the e*al+ation ofdi5e'ent pe'iodontal t'eatmentp'oced+'es.

These methods ha*e -een +sed in s4+i''elmon0e#s and also in la'$e' p'imates.

pSelection

1

pp ca on o an ma mo e s npe'iodontolo$#


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Pe'iodontal tiss+e 'e$ene'ation st+dies Animal models can-e +sed in the st+dies conside'in$ $'o&th facto's% -one

$'afts,mate'ials% $+ided tiss+e,-one 'e$ene'ation% EnamelMat'i3 De'i*ati*e 8EMD9 application% colla$en,s#ntheticmem-'anes% Bone Mo'pho$enetic P'oteins 8BMPs9application% pe'iodontal tiss+es% 'e$ene'ati*e facto's andosteo$enesis -# means of -iolo$ical cells.

Bone !ealin$ In*esti$ations Fa'io+s animal models can -e+sed in the st+dies conside'in$ -one healin$ of a'ti6cialdefects.

Pe'iodontitis Model Desc'iptions 2e''ets can -e +sed as

models to e*al+ate the assessments in pe'iodontal defects%e3pe'imental,ind+ced pe'iodontitis o' $in$i*itis%inammato'# mediato's in $in$i*itis o' pe'iodontitis%compa'isons -et&een h+man and animal in te'ms ofpe'iodontal patho$enesis and o'al patholo$# in*esti$ations.Since the co+'se of the pe'iodontal lesion in fe''ets follo& a

simila' path as in h+mans

1

Application of animal models inpe'iodontolo$#


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Calc+l+s fo'mation st+dies Bea$le do$s% 'ats and fe''etsco+ld -e s+ita-le fo' calc+l+s fo'mation and 'esea'ch st+dies.

Implant St+dies Fa'io+s animal models can -e +sed in the

st+dies conside'in$ e*al+ation of di5e'ent t#pes of dentalimplants.

Bone Re$ene'ation In*esti$ation Non@h+man p'imates can-e +sed in the st+dies conside'in$ -one ind+cin$ mate'ials.

Pe'i@implant Tiss+e St+dies Rhes+s mon0e#% c#nomol$+smon0e# and -a-oons ha*e -een +sed to st+d# osseointe$'atedo'al implants d+e to the possi-ilit# of o-tainin$ -loc0-iopsies

1

pe'iodontolo$#

Concl+sion


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Concl+sion

1

The choice o' selection of animal modeldepends on a n+m-e' of facto's 'elatin$ to

the h#pothesis to -e tested -+t also on mo'ep'actical aspects associated &ith the p'o/ectand &ith p'o/ect sta5 and e3pe'imentalfacilities. The +sef+lness of a la-o'ato'#

animal model sho+ld -e /+d$ed on ho& &ellit ans&e's the speci6c 4+estions it is -ein$+sed to ans&e'% 'athe' than on ho& &ell itmimics the h+man disease.

Concl+sion


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Toda#% -'ea0th'o+$hs in medicine a'eth'eatened -# some &ell@6nanced animal'i$hts,&elfa'e o'$aniations that see0 to

impede o' stop the +se of animals in 'esea'ch%testin$% and teachin$

1

Concl+sion

B+t the comple3it# of li*in$ o'$anisms'e4+i'es 'esea'ch and testin$ on animals

that a'e simila' to h+mans to attain 'elia-leand e5ecti*e 'es+lts. Blindness cannot -est+died in -acte'ia o' hi$h -lood p'ess+'e intiss+e c+lt+'es.

Refe'ences


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Refe'ences

Pe'iodontitis in man and othe' Animals A compa'ati*eRe*ie&. Ka'$e' 7: Pa$e R.C. Sch'oede' !.E.

Non !+man p'imates +sed in st#+dies of pe'iodontal diseasepatho$enesis a Re*ie& of lite'at+'e. H. Pe'iodontol7;==@>

La-o'ato'# animal models in Pe'iodontolo$#. HCP 7:;;>@;=

Mic'o-iolo$ical and imm+nolo$ical aspects of e3pe'imentalpe'iodontal disease in 'ats). H. Pe'iodontol 77:>@;.Kla+sen B.

Simila'it# of epithelial 'elationships in the $in$i*a of 'at andman. H. Pe'iodontal 7> == @. List$a'ten

Chlo'he3idine $l+conate to inhi-it dental pla4+eacc+m+lation in Macaca speciosa. H. Pe'iodontol 7 :7@::. Reed M.H

1


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T!ANK YOU


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Resea'ch methodolo$#

Cate$o'ies of 'esea'ch

1

(si& )""lied

*m"eri&l Theoreti&l

+unttie +ulittie

Scienti6c method


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Scienti6c method

3efers to series of standardied procedures used inresearch to increase likelihood that information gatheredwill be relevant reliable and unbiased.

Steps

8. )roblem formulation9. :ypopthesis formulation

5. ;ata collection

riting a report

1

Data collection


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?ualitative?uantitative

;ata collected on basis of attributes

,r 'ualities like se( malocclusion

cavity etc

?uantitative data can be discrete or continuous.

;ata can be collected through

a.)rimary source@ data obtained by investigator

himselfb.Secondary source@ data already recorded is utilied

to serve the purpose of objective of the study. g opd records

1

Data collection

;ata collectedthroughmeasurements using

calipers arch lengthwidth etc

hat is a PICOT V+estion"


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The )$!,T 'uestion format is a consistent AformulaA fordeveloping answerable researchable 'uestions.

V+estion Templates fo' As0in$ PICOT V+estionsP )opulationBdisease 2 i.e. age gender ethnicity with a certain

disorder4

I $ntervention or Cariable of $nterest 2e(posure to a disease riskbehavior prognostic factor4

C !omparison@ 2could be a placebo or Abusiness as usualA as in nodisease absence of risk factor )rognostic factor D 4

O,utcome@ 2risk of disease accuracy of a diagnosis rate ofoccurrence of adverse outcome4

T Time@ The time it takes to demonstrate an outcome 2e.g. the time

it takes for the intervention to achieve an outcome or how longparticipants are observed4.

6ote@ 6ot every 'uestion will have an intervention 2as in a meaning'uestion4 or time 2when it is implied in another part of the'uestion4 component.

1

E3amples


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>hat is the duration of recovery 2,4 for patients with totalhip replacement 2)4 who developed a post-operativeinfection 2$4 as opposed to those who did not 2!4 within therst si( weeks of recovery 2T4F

&re kids 2)4 who have obese adoptive parents 2$4 at$ncreased risk for obesity 2,4 compared with kids 2)4without obese adoptive parents 2!4 during the ages of veand 8G 2T4F

;oes telelmonitoring blood pressure 2$4 in urban &frican&mericans with hypertension 2)4 improve blood pressurecontrol 2,4 within the si( months of initiation of themedication 2T4F

1

!#phothesis


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& supposition arrived at from an observation or reHection.

Methods of fo'min$ an h#pothesis

%ethod of di*erence

%ethod of agreement %ethod of concomitant variation

%ethod of analogy

T#pes of h#pothesis

6ull hypthesis

&lternate hyphothesis

Animal Models in PR

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