PHARMACoLOICAL8 ToviooLObicA SeREENNG MET HObS

MPT 1083

ATURE
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morning

Long Exercise Book

 Respinatony Model

Model ton CoPD_Ciganet9e Smoke induced model tor CoP

Taineiple lOPD is chanactetisBd by sevene
distecascd nhiah rnay maniest as bronchi-is nespinatany
and cmphysemo
Gronak ts on in?lammetHon brone hs is an esental featne
o disease ohich is -trigge ned by a partielte martten depon
=ted lagly in nespiriatory noed o a chronie smoken. The
Condition s prúnaily due to the expaune o -he Smoke
ciqnete and is ansociaded ath hypen seenetion o mueuAS

* Wth hme he condition may aggmavale to cmphy Sema.

* Frormn
<pidemialagy peind vicuo a'qanete smeke ts chosen
as an inducen so as to gain validity Along ith
bonchas he d'sease is also assoetated wh museulan the inlamed
ypenplaia and fntennal thickening
alyealan duet . The incneased asculatune bianchtal vessel and
alaag wh aternaion
in punonony arhieteetune can be eaosidenc d as inducen ot
disease Severt ty Hence -the choiee ciganette Smeke as
nducen quite justi7yable in -ihe coaiad o tholegieal
Jeatunes asociaded with cOPD

Yethodalog
kpics chotee i- qutnea Pig om nats migh be wed fon
Cspetmen

*The antmals ane capscd to cigaecte smoke eithen io an

Dcude chonie schedule.

For aote studies he animals ane Laualy exposed to he smo ke

ingiata glHen aigare-ke oonteiaing sandand armcuod
and nicotin
da
-and he Smeke is
qereaed rom
a olleten 5 elgarete fon a standand caleny oý Six
antmal's.
 animals_ncead fo. be eaposed to the
* fom ahrerie studfes
e? onementioncd bnand yon a dsng
Smoke ame tHe caninuing
iganete pen day gotm 5 dhys a wcek
Lpto 7 morths .
veelh lavgye
cpsune pesiod broncho alluids
*# eed ofthe eUde he aumuladed in dh lenen
to be done to
Hegpiratory tact
chemsk;.
along widh yto kineCanardbe
* The omtioidant cCencartrnechonestinstedatchich
inhe Crudedane
co Melaled wth -he ametonade poeohial af he cg

A he animal shoaiog Meduced aohoxidant cecentotioe in

ith in pto kioe and
ehemokn Concenstateo will fodcate «teti vcness he
schetule and Suchan?malet|/ be iocluded in
he study since hein Sensthvity to he induee gets
coninmed io the ptocess
ia
fon testing amelionahoo the aimals oeed -to b Sonded
nespeeivegroups and cvaluation is. based on -he. pana medens
alncacdy eakanedl aang with histapathelegical cvaluathon of
frtacheal. musculatune

* Nblume dersity o moenephage dceumulaia aso needs to be

estinade d o measLne he exdknt c? the

Maiicatiens
* The orDginal model has beeo modificd
on the basis a metens
estimoted `such as inenease inphophodiestenase (PRE4) en24me
Lohichcan as tndez of serertity
*In onchen medieaton CoPD hes been. Suceessfully induced in.
als Au asdilla ten elastase fo cembinotion wth Se, ohieh
foucd to t aggravett nduce leasen ideotcal ofo human
(ike
bron chii s prnc eeling emphysema
 h anathen modifieathen emphyscma in animals
aggtieva td wfth streptoaeceul pnumeniae ce inteeten
which onms the bases induced cOPD midels
o_LPS

Cnitical Asess menrl

* The propemtten ot nicoine ond tan in
imporrdand gon contnelf ng Sevenity f yrmptons since the
medel is associated h high' eretality nade
*In case o sevene ep asphyzla -he animals nccd to be kept
in sepanate chamken pnefenentha y tth zyqenatian te

faeili tate nevival

* Cane shauld be daker animals shaaing ans y
oneathlessnesi

Elastase inducedemphysema model

Tstoetple t- Enphyna a 'a candrHon chanten'zed by wide spmadg
breus tssue in ulmonary ssuc assoatade d with lass a

clashety enayme pnévtlaqe Lahteh seleefively deatrey hx pretein

Hespoostble or pulmonany' elastieity h phystolegiea isue theenhance
aatity o´elastese ts ghtly eotrelled by he iypsin
he aatty o elastase ohich destro y the ea stn pretein
Heneeelastase colagen peveleat io pulmsnany Hssue
Can be used feateinducer ieemphysema

fon todueton human neuthopbt l clastase is -he besd chotee

sinee Bens he achantage grcaten skstni buchiarn in ihe
daget#ssue theugh poneioe pancneatie elastase has also been
gor hepuripoSe The clau is Considened to be an

fodteated by h estimate 4 elastese od olhen in?lammaroy

mediatorts.
 Jrocedune i albino ras.
Speaies4 CheieeMale wssten

Netadeiegy
* Animals ave asigne d to eapeetive gop
and theated with

hurman neurtrophil elastase at a

dese
cilhen Salin e
200 Irtennoienol unid

haemanthogi<
* Soon Hen the en2yme odminietation he accumuletian of
qets aetivated, eadoq .to congesshon and
ielommatar1y redades ta the ouen respiratomy noei
llowcd by spanade dyspnca
* Fon betten blty a symptoms elastase nced sto be Spmead
usiden portioo o ttachea hiah is oahie ved by uie
micnasprayo
* The animals ane Sacaified & wecks otten f the
eta and palmooary Asue is subjeekd to histapethalgia
eraluateo

* Hoemmenhoge is neated as wide sprand hiataleglcal. dem

Qcceompanied by netve phil accumulaian in the penany ts
tissue ta osoafotion wth aretia cbanges
* Exteo o tise ncmodelng is daken asa paramelen :
evaluation Lung velume s also esttonate d in denms of
funetonal
* Broncha olveo lan lauge s alsa penfermed he extaad o
rtapulmapa try exaudate to delekne neutropbil count ar
hacma globin cenknt
* Model jen emphysema has been modied by using difonesi
indueen as el as by aking end poin + Jorn masunemerts.
Platelet detved growth foator A s considened
piveta o Hecperaion myofbrobkbut genenaten has been
Siggested on re liable mankens

* Mgaton and aetyation o neutrophil.

Caitiaaldsses meosl -
* lo ploce of Toneaat pancneata elastase ; human etaph:l
elastose be sed
gon greoten distribuion o damget
elasdant.
AsTHMA
Bmonehtol Hypen neactivi-ty in Gunco Pias
Btn'ple
* The dest meand to estonade the potentaI a drug unde
ion to Heved boelk the
investigt
to allessgens tke histamfne Con yulsfons duc to asphyz'a are
death ginea p epesed to aleagens whieh may leod to

# The canulstve episode fs as

dyspocs and ngiy teamedypiclly
pHoaecded by a state o
phe -conulsive dyspnea (eD)
sdate

* he tfme o cnsed ohts state is

gencra lly taken as slhe pana
-meter Jdgemerl Pntkls madel.The drug s satd to be
podenal anti-asthmatte i Hcon de lay -he onse- o PCD
along th -he cortrol o asso cfaled
ymptems.

Spetes of Chotce ’ Male Grutnca gs.

 Mehadelort
* Test
isuncertaken
kohich
in a poctaly datgoe d fahalaton chambc,
Senves -lhe enelasuns faY. detveny o allegen:
Suspended în the ortm o mist so as to ensune Susteîned
expesue .
* Afn lw fo lhe enelosuhe ismafodained at a constant Mate
1:5 in and he enctesure ls dRided ioto 2 cubiaals
Sepanaded by apengorated paretioo Aall ahfeh senves_ os
meanS.
to the fo deliveny og spasaagens fn -he Jonom acresl
othert chambèn.
* The atnal is plosed to one e
Hhe chanmbens and penfonatien
on he stpamating boal fs gpcn leiog the nesal a the
Cosieal Qask deltvern a metencd dose o spasmagsos pen
aatuattoo The conical lask 2s Rled h o%
o hisla noine atached to an solutioo
ultnasoud nebulizen.
Fon settng the base ne
-the animal is erposed to a mis
ollegens cneatkd by he nehultzcn uati tsheuss the
* Upon ezhibition o such
symptoms che animal nemeve d
eharaben and allowed to nevtve în
pRO air.
* Subseguenlly he antmals
ane placed fa anerthen
kchens
soluetfenhey ane expased -hreygh
o dest
chamben
dnug on gtandarnd .and
upan epasu ne to time of onse7
CIheneaten în usual ashianSpasmegen is estfmatte d

The model has bceo

Briewn Natuoay Rods. coicdot Sucen lly in sensichaed
*Immune logiea! factons nelaled to brenchial bypen octtity ane
vafous and henee octorn speeifie leison s in -the rrspinatory
Hroct hos been chanoc-teni sed Yom neenence .

Cntteal Asse sument i

The ne bulize M preSswne needs to be optmided and he boso
onset needs to be opttmtsed aso wth Hespeet t
the
ealany
hoNZETT_KossLER
use d.

MoDEL OF BRONCHOsPASMOL73s
* Thts methad is based on rthe quantitattve estmation atr
volume ahanges of a iving anñmal in a clesed ystm using
pae ap he respiratory fassage capable causog andpresune
denence hus alawing measunemen oq presune
enceSS stfafo -he closcd cineut

* Bnonchespasrm suo lly deeneases othe elume o} inspined ainthene

-by Snercasing he volame eg The parmedn comnelate
the dseose and the drug ts lenmed
to bepotential anti - asthamatic i it Can neduce the velume
eree an

Methodelagy
Trceedunei
* The antoals ane anesthetizcd wth unethane and the ttachea
is expauel by midltne Socisien.

*Absence o ony spontanceus nespinatory pulses 1s ascerdaina

prten
The cxpase d tnachca is Cannalated with a tridenl onnua
-tom. One am Conneetled to a nespiatorty
pump he orthen to trans ducemohile the 3* one
upto he Mespinarto My passge
 fegueney f
* The antonal is ani eialy ventlated at a
60_stho kes per mia

colleels oto tbe cubical

* Excess ain not taken ep by lungs
Qnis Necon ded by a
easien kveny
akn veio is abo Cannulated fon
test substance Camotid andeny cannulatkd fa.
measuni blood pressune

* Each animal is placed in supne pasition in cesed eentinen

to 0.25%. histarnine soletien sprayed dieathy iato epen
trachea one haun aten she dng
expasane
The onimals shos a head drop as a sigo asphyia

ioto Consideratioo a
* he volume o excess ain is alsa takeo
indicaded by he ttansducen
* The pctkohal ant- ashmake can pralanq the lateney
wth Hhe subscquend deancasea ain

ALLERGleAsTHHA MODEL
Meac hon hit
I
seeming hanmess allengia.
Shous up upon being Sensitzed to asthma is asoai ated
envineomeotal tetggchs.The allengics
fo ovon ScCretor
hypen esponics to alengens leadting
Mucus bloc king the
allangens thi ) ypollens hesehon ioclade
* Sprfe
ovalbumio (c¡g h%le
pe
and abo latez
 Troce dure -
Speaies a ehotee i- Male wise ats

Methedology
* The antmals Sensitzed to the allemgen by 3 consebetive iy.
deses o oval bum)o and a chalenge
wth the game
twicea week oVeH peniodo 2 weeks allergen
*.Some wene also maiotained as eortol.

Sympeamaie evaluaton is camni ed otl on weck 1 and

wek 2 to ensune /he persisdonce o air oay
inglamma
Han.

# fon evaluatoo dteneotal cell couns ane eannicd out

On btoncho alveola exeuded eallee ted 48 houns aten -he
last alleygen ohalleng
The brorcho aleclan Kavagc qluid s uscd gorn he
estmatongytekines Uke 1Í-4, 2L-5 an TNF &and
aresubjeeted to histo poriholegy and fmmuno his te pat tho lo
gical. onalis to ascerdoin letson spreic polhogoesBs.
Bleosyein lndueed Palmorany flonosis
* Falmonasny bnosts is often asoci oded ith asthma sohiah
indicates he chroniety o the d'scose. Some antmals ane
pataln
ahiah
Suseepiale to gilbrosis indueed by bleamyein.
ineude Synfao hamstes, albino rats and miee
Howeren the qolden Synfan hamsden is theahosen speeics
sensitiväty
Mehadol
Speeiesggy o? chtce -Male fobden Synion Hamsten.
 iostille d
Prgtcdune
* The aninals Otte kegd
on standad dietaod werte

intratrechea
bleomyein .
day3,7 o, 4 and 21.
* The aninals ahe soanijiacd
biechermical esthnatioo subseguent
subjeetkd to evaluatoa incud Lipid
hamegenísatisa Thepasamatens aettuity and sone.
penexidathon, pnelfne evaluatioo is also done wih
hycaxy prnoline Histapathal
bioahsmieal caluatian.

An incneas e o pnotein io deamyein treated gnoup eshbli

-Shes sucaeul eata blis bmend o pathelegy
seyena speoies
mode l has beca caried o t io
k The
alder nime
dexametba sonc has beeo tested as poteatia
k Law_ dose
by sthts model
ame lionato a the condiion
Cattieol Assessmen1i hleamyein ioduecd
laten o oni dotive damoge to
* The ne chanoatenise d by this model.
be
rbrosis
 INFLAMMATORy MobEL FoR Se EEN ING ANT
IuFLAMmATORY Ac TIvIT Y
3.|.22
Qhat the mode on
actiity Senechîng anti ingommatony

Ghenenaly 3 ypesinglommoction produced.

lommartion
b.
Canagecnan
Hisiamine
foduae d pacdema.
iodueed
9 *istom:Nedema.
(5-HT steod
e aiadykioin induce d paw edema.
d. Deztnan oducedpawedema
&Lypopely sacehanide indueedaw cdema (Les)
Anaahidonic induced ca edema
Croon oi indueedean edema (TPA)
Oza2one ynduced Cay edemo
cy Acertie aeid iodueed vasculan permeabi Gity.

i) Sub aourte inglammastion

a Granulsa pauch mode L

Cottanpallete induced granulema

b. Fozmaline ioduced paw edema
C. CFA
Spduced anlhatis (Cemplete eund
Adjaven).
avngeenen induced paw edema. Advandog)
T4 9s themostprccned model inglomma fian as
Ihe in ormmation pho duced is neproduei ble.
Hutt Haltiple meehanism iaveed ohich makeg
hese model Os.
pri iminy choice gon scnecning
Gni -ilannmoto ruy gent
As the ,prodced ?4 allow lhis
biphasie nespone
model to amteipot biologicok -laget hat ane
prtobable gr est
o the dng inglomma tion,
 model s suitable or teoting the drug
Snhibit Cyelooygeno se.
Lmftatico n
(1) Thes mode needs alleost 1 week fom moi ntaror
anfmaS boone start the cxpenimend .
(w) Taned peso o ane needed
to iovestigateresut
eproducible
the acti,
fom hecemdinq sBable and

DextronInduced Paw Edema!

Proce dune,- In this mode administraion of dextan rele.
Ses mediatos (Gke histamine and Senotonin via
Soeneesed vaseulon permeabiity Ond kinin aetratier
eohene Hhese mediatons get 'ioteracted with.
Hespective Heceptoy Lti, ty 85HT,) which
develop the osmotic edema havig minimua
neutnoehi! and proteio. This mode eods to
develspmenrd fast and Shont dema
Adyandage ai
-Ihis model develop cdema heleasing by
histamine and Sene tonintle nce
-to evaluate the +his model usEd
anti
having onth hisdominic inglammatorvy actity chuge
aso used analyse he hesut cbtained ty
paw e dema induce d by Caunageenon.
Disadvantage i
(3) hs model is not sto ble for the
Qnti n9larn matore eect ethen han shouwirg
anti bstamini
Cke mechaniSm.
 Cnoton 9 Induced Ean Edemo
Phocedne i
CHoton oi causes cdema and ane uscd to
evaluate anrli lammatoty octBon
TPA model is used to study Syithestieond
ani iozlommao Cenpound. osodatan Js coused by
tepicaluse wbicb îneneases Prmea
-biity blecd vessel tesulting înte îux
neucttre phil hat ptoduce echosonatehich
TPA
helease s histooine and serotonin. ohile the
Causes Protein acfivationohich
MAP K
nespensi ble on aetvaton
Aetivate d Protein Kinase) as welt as phesphoLye
A actvaton
Adeadege
) Stencidal & no0-stensidal
onti tn lommatoi dtre
Can be SCneerdpropenly by csicg his medeL

isadvantage
ane
genenaly Saanieed aten experiment