ExperimentalPharmacology

 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

HP\HTFJHKRNA \@NTJNCIAIMV FKRTIBXCRFIK RI HP\HTFJHKRNA \@NTJNCIAIMV NKB BFOOHTHKR ANDITNRITV NKFJNAS \`ntjnciaim7 Fr fs r`h scfhkch }`fc` bhnas }fr` r`h srxb io btxms }`fc` fs bhsfthb

otij n mthhe }itb $\`ntjncik$ }`fc` jhnks btxms / $aimis$ jhnks srxb+ Hp|htfjhkrna \`ntjnciaim7 Fr fs r`nr dtnkc` io |`ntjnciaim }`fc` }`fc` bhnas }fr` r`h

hoohcr io btxms ik afvfkm a fvfkm ssrhj+ Fr cnk dh srxbfhb xkbht `hnbs7 n&

\thcafkfcna \`ntjnciaim7 bhnafkm }fr` hoohcrs io btxms ik nkfjnas+

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Cafkfcna \`ntjnciaim7 bhnafkm }fr` hoohcr io btxms ik `xjnk afvfkms+

R`xs fr `ha|s fk xkbht srxbfkm r`h knrxth io btxm ncrfik nkb r`h xk*narhtndfafr io r`h afvfkm ssrhjs ri r`h nrrtncr d c`hjfcnas r`nr shtvhs ns r`h dnsfs ik }`fc`7 n&

Kh} r`htn|hxrfc nmhkrs nth bhvhai|hb /

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Ripfc ciksh~xhkchs ciksh~xhkchs io c`hjfcna hp|isxth jn dh ncrfvnrhb+

R`h hp|htfjhkr cnk dh cnttfhb ixr fk }`iah nkfjna fk vfvi& it fk fsianrhb itmnks fk vfrti&+ Iahcrfvhs oit hp|htfjhkrna |`ntjnciaim7

>+ Ri |tivfbh scfhkrfofc }hfm`rfkm io n btxm oit frs xsh+ 4+ Ri nbb kh} / dhrrht btxm fk r`htn|hxrfcs+ 3+ Ri ++++++ / bfscivht kh}! sfj|ah / dhrrht rhc`kf~xhs oit hp|htfjhkrna+ 2+ Oit dfinssn nkb srnkbntbfwnrfik io btxm+ Dfinssn 7

Hsrfjnrfik io r`h |irhkc io nk ncrfvh |tfkcf|ah fk n xkfr ~xnkrfr io |th|+ it bhohcr / xsfkm dfiaimfcna jhr`ibs fs eki}k ns -dfiaimfcna nssn it Dfi nssn+

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

Bfoohthkr Anditnrit Nkfjnas Nkb R`hft N||afcnrfiks Fk Hp|htfjhkrna \`ntjnciaim 7 Anditnrit Nkfjnas 7

R`hsh nth r`ish nkfjnas }`fc` cnk dh xshb nkb thnthb jnfkrnfk& fk r`h anditnrit xkbht sxfrndah cikbfrfiks+ R`h cijjik anditnrit nkfjnas nth tnr! jfch! mxfkhn |fm! tnddfr otim / `njsrht+ Ir`ht nkfjnas xshb oit hp|htfjhkrna |xt|ish nth cnr! bim! jikeh! |fmhik hrc+ Sfkch aikm nkfjna hp|htfjhkrs `nvh dhhk n jfah srikh fk nbvnkchb jhbfcna thshntc`+ Nk it hvht nkfjna fs kir sxfrndah oit hp|htfjhkrna }ite+ R`hth shahcrfik fs dnshb ik r`h oiaai}fkm ctfrhtfn+ Sfwh7

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Sjnaaht nkfjnas nth |thohthb dhcnxsh r`h nth hns ri `nkbah / ahss

~xnkrfr io btxm fs th~xfthb+ Nvnfandfafr7 Nkfjnas }`fc` nth cijjika nvnfandah s`ixab dh shahcrhb h+m+

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otims! tnrs! tnddfrs / bims+ Shksfrfvfr7 Nkfjnas }`fc` nth shksfrfvh ri btxms xkbht rtfna h+m+ mxfkhn |fm fs

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shksfrfvh ri hoohcr io `fsrnjfkh+ S|hcfhs7 Fk tnddfrs fkrtnchthdti vhkrtfcxant fkghcrfik io 8*@R fkbxchs n ai}htfkm

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io rhj|htnrxth! dxr fk cnrs! fr fkbxchs ohvht+ 

Hr`nctkfc ncfb fs najisr fkncrfvh fk tnrs! hpch|r nr `fm` bishs! dxr ~xfrh ncrfvh fk r`h bim+

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Oiaai}fkm r`h snjh bish io `hpidntdfrikh |ht xkfr dib }hfm`rs! r`h nvhtnmh sahh|fkm rfjh io tnrs fs ndixr shvhk rfjhs r`nr io jfch! nkb fk r`h bim frs hoohcrs ansrs oit `ixts+



Mxfkhn |fm nkb `xjnks nth 80 jm+ |htchkr+

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

Fsianrfik it mtix| `ixsfkm7

Bish io |hkri`ntdfrikh it |`hkidntdfrikh! }`fc` |tibxch oxaa `|kisfs fk fsianrhb jfch! |tibxch jntehb srfjxanrfik }`hk r`h nkfjnas nth mtix|hb+ R`h C_S dhcijhs jith ths|iksfvh ri fsi|thknafkh fk siafrnt `ixshb ?*0 }hhes& tnrs cij|nthb ri mtix| `ixshb tnrs+ C@NTNCRHTSRFCS / NB_NKRNMHS IO BFOOHTHKR NKFJNAS f& TNR Tnrrxs kitvhmfcxs&

Nadfki tnr fs ikh io r`h cijjikhsr anditnrit nkfjnas sxfrndah oit hp|htfjhkrna }ite  dhcnxsh io frs dhcnxsh io frs sjnaa sfwh / mthnrht shksfrfvfr ri jisr btxms+ Fr fs nasi r`h jisr srnkbntbfwhb io naa anditnrit nkfjnas+ Fr cnk dh xshb ri idrnfk |xth nkb xkfoitj srtnfks nkb fs oixkb ri dh vht srxtb ri }fr`srnkb aikm |htfibs io hp|htfjhkrnrfik xkbht nknhsr`hsfn+ Fr fs sjnaa fk sfwh cij|nthb ri ir`ht nkfjnas si btxms nth th~xfthb fk sjnaa ~xnkrfr+ _ijfrrfkm chkrth fs ndshkr nkb si btxm cnk dh nbjfkfsrhthb itnaa+ Mnaa danbbht nkb riksfas nth ndshkr+ Dhcnxsh io r`h ndshkch io mnaa danbbht fk tnr r`hth fs cikrfkxixs oai} io dfah fkri r`h fkrhsrfkh+ R`fs oncfafrnrhs r`h srxb io btxms ncrfkm ik dfah! c`iahsrhtia thndsit|rfik+ \nkcthns fs bfooxshb! r`hthoith bfoofcxar ri |tibxch |nkcthncrij+ |nkcthncrij+ Fk srijnc`! oxkbxs / |aitfc |ntrs `nvh cahnt afkfkm dhr}hhk r`hj+ R`h mnsrtfc ncfb shcthrfik fs cikrfkxixs+ HP\HTFJHKRNA XSHS7

Nbxar }r+ >0+ \sc`i|`ntjnciaimfcna \sc`i|`ntjnciaimfcna srxbfhs+ 4+ Srxb io nknasfs io nkrfcikvxasnkrs+ 3+ Dfinssn io vntfixs `itjikhs! sxc` ns fksxafk ipricfk! vnsi|thssfk hrc+ 2+ Srxb io ihsrtxs ccah! jnrfkm dh`nvfixt nkb ancrnrfik+ 8+ Srxbfhs ik fsianrhb rfssxh |th|ntnrfik afeh xrhtxs! srijnc`! vnsbhohthks! nkiciccmhxs nkiciccmhxs oxkbxs srtf|! `hntr! hrc+ ?+ C`tikfc srxb ik daiib |thssxth+ =+ Mnsrtfc ncfb shcthrfik srxbfhs+ 0+ Srxb io `h|nriripfc nkb nkrf`h|nriripfc cij|ixkb+ 6+ Ncxrh / c`tikfc ripfcfr srxbfhs+

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

D+ MXFKHN \FM Cnvfn |itchaaxs&7

Fr fs bicfah nkfjna! `fm`a sxsch|rfdah ri RD / nkn|`anpfs nkb nasi `fm`a shksfrfvh ri `fsrnjfkh nkb |hkfcfaafk+ Fr th~xfths hpimhkixs nscitdfc ncfb fk bfhr+ Hp|htfjhkrna xsh Nbxar ]r+ 2+8*3+< Em+ nmh sxfrndah oit hp|htfjhkr 8*? jikr`s+ >+ \timhk rhsrfkm 4+ Dfi nssn io nkrfbfndhrfcs! cxtnthoitj btxms nkb shp `itjikhs+ 3+ Scthhkfkm io nmhkrs noohcrfkm cn|faant |htjhndfafr+ 2+ Fttfrnkc rhsrs+ 8+ Scthhkfkm io nkrfripfc nmhkrs nkb rhtnrimhks+ ?+ Srxbfhs thanrhb ri th|tibxcrfik nkrfohtrfafr nmhkrs&+ =+ Fsianrhb |th|ntnrfik afeh `hntr! bxbhkxj! fahxj! Ofkeahjnk |th|ntnrfik+ 0+ Srxb io aicna aicna nkhsr`hrfcs sxtonch nknhsr`hsfn& 6+ Srxb io jfirfcs / jbtfnrfcs jbtfnrfcs H& @NJSRHT Jhsictfchfrxs nxtnrxs nkb Ctfchrxaxs mtfshxs&

R`h `nvh s`itr dib }fr` s`itr ahms / rnfa+ R`h sefk fs aiish nkb civhthb }fr` bhksh s`itr sior oxt+ R`h c`hhes |ixc`hs nth |tijfkhkr / hprhkb x| ri r`h s`ixabht thmfik+

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

HP\HTFJHKRNA XSH7 nbxar }hfm`r 0 jikr`& >+ C`fkhsh `njsrhts `nvh ai} c`tijisijh kxjdht jnefkm fr xshoxa oit criaimfcna mhkhrfcs rfssxh cxarxth / tnbfnrfik thshntc`+ 4+ Thshntc` ik bfndhrhs jhaafrxs 3+ Thshntc`

thanrhb ri vftiaim! fjjxkiaim nkb fj|ankrnrfik srxbfhs+

2+ Dfinssn io |tisrnmankbfks+ O& OTIM Tnkn rfmtfkn&

Ikh io r`h jisr cijjika xshb hp|htfjhkrna nkfjnas fk |`sfiaim! |`ntjnciaim nkb ripfciaim+ Fr `ns dhhk xshb fk hp|htfjhkr oit 4+

Srxb io fsianrhb rfssxh sxc` ns thcrxs ndbijfkfs jxscah nkb `hntr |th|ntnrfik+

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Srxb io btxms ncrfkm ik CKS

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Srxb io thrfkna ripfcfr io btxms! afm`r dahnc`hs t`ibi|sfk fk hh }fr`fk ikh `ixt nkb fs thmhkhtnrhb }fr`fk ikh `ixt fk bnte+

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Srxb io btxms ncrfkm ik khxtijxscxant gxkcrfiks xsfkm mnsrtikhjfxs! scfnrfc jxscah khtvh |th|ntnrfik+&

M& CNR7*Fr fs cntkfvitixs nkfjna thanrfvha hns ri idrnfk nkb ri xsh oit hp|htfjhkrna

|xt|ish+ R`h |`sfiaim io cftcxanrit / khxtijxscaht ssrhj fs vht jxc` sfjfant ri r`nr io jnk+ Fr `ns `fm`a bhvhai|hb kfcrnrfkm jhjdtnkh }`fc` fs cikrtncrhb d sj|nr`hrfc khtvhs+ khtvhs+ Jit|`fkh |tibxchs |tibxchs hpcfrnrfik io chkrtna khtxixs ssrhj ssrhj fk cnr+ HP\HTFJHKRNA XSHS7*

>+ Ncxrh hp|htfjhkrs oit r`h btxms noohcrfkm D\+ 4+ Dfinssn io KN xsfkm s|fkna cnr& 3+ Srxbfhs ik mnkmafiks daicehts xsfkm kfcrfrnrfkm jhjdtnkh fk vfvi& 2+ Srxbfhs ik khxtijxscxant ssrhj xsfkm mnsrtikhjfxs! scfnrfc jxscah khtvh |th|ntnrfik+& 8+ Ripfcfr srxbfhs io cij|ixkb afeh nchrnkfafbh+ @& BIM* Cijjika Jikmtha Jikmtha it Dhnmah Dhnmah bims nth xshb+ xshb+ Fr fs hnsfa nvnfandah nvnfandah / antmh

sfwhb nkfjna+ Bims cnk dh hnsfa rnjhb ns }haa ns rtnfkhb+ Fr `ns n sjnaa srijnc` nkb s`itr fkrhsrfkna rtncr thshjdafkm r`ish io `xjnk dhfkms+ Fr cnk dh cikbfrfikhb ri cntt n

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

srijnc` cnkkxan+ R`h chtvfcna sj|nr`hrfc nkb vnmxs khtvh txk rimhr`ht fksh|ntnda fk r`h rtxke  HP\HTFJHKRNA XSH*

 Mnsrtfc ncfb shcthrfik srxbfhs \nvaiv |ixc`+&  Ncxrh hp|htfjhkrs oit btxm noohcrfkm D\ nkb fkrhsrfkna jivhjhkrs hrc+  Srxbfhs ik nkrfbfndhrfc nmhkrs+ F& JIKEHV NKB N\HS* R`hsh nth r`h |tfjnrhs dhaikmfkm ri r`h `fm`hsr itbht io 

r`h jnjjnas+ R`h nknrij / |`sfiaim io r`hsh nkfjnas nth caisha thanrhb ri r`nr io  jnk+ R`h srxbfhs bikh fk jikehs nth bfthcra rtnksanrhb ri jnk+ Ciksfbhtfkm r`h `xjnk ths|hcrs! rhsrs fk |tfjnrhs s`ixab dh bikh ika fk ansr srnmh io hvnaxnrfik io  btxms dhoith cafkfcna rtfnas+ R`h nth xshb fk r`h ofhabs io |sc`i|`ntjnciaim! xtiaim! fjjxkiaim! kxrtfrfik! th|tibxcrfik! |ntnsfriaim! hrc+ G& AHHC@7*R`h bitsna jxscah io dhhc` fs xshb oit dfinssn io nchrac`iafkh+

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 QQvdipstvQcikvhtsfikYrj|Qsctnrc`Y>Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

ANDITNRITV NKNHSR@HRFC NMHKRS Idghcr7 C`ifch io anditnrit a nditnrit nknhsr`hrfc nmhkrs+ nmhkrs+

Mhkhtna nknhsr`hrfc nmhkrs dtfkm ndixr aiss io naa shksnrfik |ntrfcxanta |nfk naikm }fr` thvhtsfdah aiss io cikscfixskhss+ Cikscfixskhss fs thmnfkhb norht r`h nmhkr fs jhrndiafwhb it hpcthrhb+ N mhkhtna nknhsr`hrfc oxaofaa r`h oiaai}fkm th~xfthjhkrs7 n& d& c& b& h& M+

Fkbxcrfik io nknhsr`hsfn s`ixab dh ~xfce / |ahnsnkr+ Fr jxsr `nvh aikmht bxtnrfik io ncrfik+ R`hth s`ixab dh nbh~xnrh jxshah thanpnrfik+ Fr s`ixab kir fkrhtohth }fr` hoohcr io btxm xkbht srxb+ Fr s`ixab dh c`hn| / kik*fkoanjjndah+ NKNHSR@HSFN IO R]I RV\HS7

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_ianrfah mhkhtna nknhsr`hrfcs7

R`hsh cixab dh af~xfb afeh hr`ht! `nair`nkh! hr`a c`aitfbh! rtfc`aithr`ahkh! mnshs ns K 4 I! hr`ahkh / ccai|ti|nkh+ R`h nth kir xshb cijjika fk hp|htfjhkrna nkfjnas! dhcnxsh r`h th~xfth ciksrnkr jikfritfkm nkb cisra fksrtxjhkr shr x|+ Hr`a c`aitfbh fs tntha xshb fk hp|htfjhkrs io tnrs / cnrs+ 4&+

Kik*vianrfah nknhsr`hrfcs7

R`hsh nmhkrs nth jith cijjika xshb oit |tibxcfkm nknhsr`hsfn fk vntfixs nkfjnas dhcnxsh fr fs hns ri nbjfkfsrht r`hsh nmhkrs nkb ki cij|afcnrhb rhc`kf~xh fs th~xfthb+ Cijjika xshb nmhkrs nth*c`aitnaish! xthr`nkh! dntdfrxtnrhs! JmSi2! |ntnabh`bh hrc+ f&

C`aitnaish7

Fr fs r`h cij|ixkb io c`aitna nkb maxcish |th|nthb d `hnrfkm h~xna |ntrs io  nk`btixs maxcish nkb c`aitna }`hk dir`  c`aitnaish ncrfvh oitj& nkb  * c`aitnaish fkncrfvh oitj& nth oitjhb+ C`aitnaish fs r`h ncrfvh oitj  c`aitnaish& othha siaxdah fk `ir }nrht fk naci`ia / fk hr`ht / safm`ra siaxrah fk ciab }nrht+ Bish7 0( siaxr xshb mfvhk >+_ tixrhs+ Nbvnkrnmhs7

>+ Fr |tibxchs sxtmfcna nknhsr`hsfn ansrfkm oit 3*2 `ts+ 4+ Ths|ftnrfik nkb D\ nth kir bh|thsshb si cnk dh xshb fk cikbfrfiks }`hth r`h `nvh ri dh thcitbhb+ 3+ Thoahphs nth kir bh|thshb+ Bfsnbvnkrnmh7

>+& \iit }nrht siaxdfafr si siaxrfik siaxrfik fs |th|nthb fk axeh }ntj }ntj }nrht it >Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

Fr fs thnbfa siaxdah fk }nrht mfvfkm n khxrtna siaxrfik+ Xsxnaa 48( siaxrfik fs xshb F+J+ R`fs fs nasi sxfrndah oit ncxrh kik thcivht r|h io hp|htfjhkrs fk bim! cnr! tnddfr / tnrs+ Bxtnrfik io ncrfik fs 3*2 `ts+ Otims cnk dh nknhsr`hrfwhb d ehh|fkm r`hj civhthb fk dhneht cikrnfkfkm 8*>+ Fr bihs kir noohcr thoahps! C_S! / ths|ftnrfik+ 4+ Fr fs thnbfa siaxdah fk }nrht+ 3+ Nknhsr`hsfn Nknhsr`hsfn thjnfks oit 3*2 `ts+ Bfsnbvnkrnmh7

>+ Fkbxcrfik fs sai} si! fkghcrfik io jit|`fkh 4jm)em dib }r+ fs mfvhk! FJ 3< jfk dhoith mfvfkm xthr`nkh ns |th nknhsr`hrfc nmhkr si fkbxcrfik fs ~xfce nkb sjiir`+ 4+ Fr `ns fttfrnkr knrxth si nkfjna ohhas |nfk+ 3+ Njixkr io siaxrfik fkghcrhb ri dh antmh si `ns ri dh mfvhk nr vntfixs sfrhs+ 2+ Fr `ns bhanhb ripfc ripfc hoohcr ik ik afvht / jn nasi cnxsh nmtnkixaicrisfs nmtnkixaicrisfs

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|xajiknt nbhkijns+ nbhkijns+ Jfch bhvhai| `fm` fkcfbhkch io axkm rxjits thmntbahss io  tixrh io nbjfkfsrtnrfik+ 3&

DNTDFRXTNRHS7

R`hsh nth jisr cijjika xshb nmhkrs+ Nbvnkrnmh7

>+ Fkbxcrfik fs vht tn|fb nkb sjiir` }fr` jfkfjna hpcfrnrfik+ 4+ Ki |thnknhsr`hrfc jhbfcnr fik fs th~xfthb+ Bfsnbvnkrnmh7

>+ Fr |tibxchs bh|thssfik io cntbfivnscxant / s|fkna thoahp! d fkrhtohtfkm }fr` khtvh fj|xash rtnksjfssfik dir` fk CKS nkb mnkmafn+ 4+ Jxscah thanpnrfik fs fknbh~xnrh r`hthoith! jxcah thanpnkrs `nvh ri dh mfvhk sfjxarnkhixsa+ 3+ Nknhsr`hsfn |tibxchb |tibxchb fs io s`itr bxtnrfik! r`hthoith sjnaa bishs io r`hsh nmhkrs nth ri dh fkghcrhb f kghcrhb nr thmxant fkrhtvnas+ R`h cnk dh canssfofhb ns7

n&

Aikm ncrfkm dntdfrxtnrhs7 h+m+ |`hkidntdrikh >40< jm ) em+ io  dib }r+ fkrtn*|htfrikhnaa+

d&

S`itr ncrfkm dntdfrxtnrhs7 h+m+ r`fi|hkrikh sibfxj 4+8( n~xhixs siaxrfik fk bish io >8*48 jm)em+ dib }r+ fs mfvhk f+v+ bxtnrfik io ncrfik fs 4Q8?24308>+bic+jsYioofch+bic  QQvdipstvQcikvhtsfikYrj|Qsctnrc `Y>Q8?24308>+bic+jsYioofch+bic

Fr `ns }fbh jntmfk io snohr ns fr bh|thsshs ika r`h chthdtxj nkb kir jhbxaant chkrths+ Bish > jm)em+ dib }r+ F+\+ it 4 jm)em+ dib }r+ F+J+ fk bims / cnrs+ JNMKHSFXJ SXA\@NRH7

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C`hjfcna jhr`ib7 Fr fs r`h |nfkahss bhnr` |tibxchb d nbjfkfsrtnrfik io 

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