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1 ) ' ( %&!"#$ 0. * / -"+, + "! "#$% " & # './ "0 %1 ( )* +,-% % )* 8 %1 ( )* +,-% " # 8 +,#-9 = 5 )> 2< 31 ; : $9 *%&'(') azimakbarzadeh@pasteur.ac.ir 7 +':/. 6:<; ::1 2 3+, /89/ (,'/#0#+,-(.+,-+'/ = C'-7D,<A)= 68, $@)6/A)68,B@,'/,<A,(,4568,? >= 3+,-.#0?#"?#? : "G)H ;F +,456# (,'/#0#+,-686,>?5E ) C'-7D,< :6 :I4L+).P <; 7 I KLM(7,N 6HO 75).F,J ; )7 I %<(!) ; +,-+'/+,- 7 I7,(','/6,QRH :I6:C?$= 6: 76:):,':S T:,!/1 H6G L/F (,4).5/E )I4L+) 6:C"?68 7U ;F +,- 5= 5F W+'/. 1 <6,X;%$>(+,V, 6O U <68F [! 68 ;A,'ZH T 6C 6:86<.; 6/I[6^?. 6= 6 V!</;G)H,\4].0?"?@6C2 = <7. 6,4,E ) ;51!= 5 ).= 6,V,$@^@_@>= <??µg/ml. :+,- 5= 5;F A,Z'V'!<G)H I- IH+'/-6J. = 5Z ::" : = : :56:,H ;: ) G)H+,.I$ >µg/ml. ) G)H+,4.I0??µg/ml ; 6% )Z,%E ).I, Z+)6, ;F :,< <+'/a 6b Lc I 6Q 6 1!`H.+'/7 I 54 #3&!"#$!%& '()* #$'+!,& -./',0"1.2 $; 6/ )%<(!) 67 ;).F,J d(!)d+,-+'/ $" $"#"!
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3 -/ )? N H6 4H9 HV HD% "H#9?6 = 1-H% ;H O H H% H: Ha>. - >: 5j = 1-%?0CH% f%hq H ; "D O]-, "L% % 5H H HA H% y 5 x0 cdsm-iv-trb = u1: %( r L9 #/ Diagnostic and statistical Manual of Mental H% H I1 H: H>/ B $Q H cdisorders H H I1 H: H 1 H?% H% H >. D,d% H cdysthymiab HF5z: " D, 4% "" > O""H Ha> #ID% * di = u1 : 5H H H H/>( B Hi 4 %9 H )"H _ CH9 H phv Q # B H B H$Q O"" * B * ){x% H "H- B H Hj5?% pv ; :, =?0C H% H x H0 "Ha> )H% ',7,<, % fdf% "D = %( Ocb " -/ ;FFG% " 48 ' H9 EH9 ( H = HS*(!) ). H% H "H H #H "HD B 6 = HS "HD #,H /=.1% = DQ% D,d% H> )"Hb "H H% O"- P > ( "HD E9 ]G% #D% c/ ) )" B 6H 7 = "% )" 48 F. 2N N / (H = S Ocb " -9 E9 "D / B H Gd : 49 = ^ E9 ]G% B LH _ 5CH9 cerythemab H H%. / -, cedemab 4 = HHH0 cindurationb >"HHH K H%( EH9 H/ ]H?.O"H "H# B 0 H>/ H H% H8,D% H>/ O" 48 - #H "HD - /B?.% * = %( *: Ocb " B?S B >%48 = HH%( HH HH +,9HH/ ;*H%H _ 5V D% X N B 5% H% H/ HcIH <o!n#h #% b I' # ;H ]%H H/ Hj%OB H )" 48 " ]H^0 ; % ( ( B A5` K HL qh9 HB /I ; % ; OB /( "H,9 IH0 +,#-9 = 5 Oco7b B H HD,d% ;H *:I4L :F,I![b f = "% b ; % ;D% % r L% & ( WHO P 4 c" 6 ]?. / s HL ;HD9 B H$Q OcJb "H 4H8 H5% ]-9 = "H%H ]."0 " _ 5V D,d% % B DQ EV #@ /B 9 X/ )% 3 "H% curinetoxicoloyiesb H/H H H8% H` H/ H5 U C% 4"6 #?% "#% H D,d% IV EV #@ O" B %1H #% = %( OB > 48 X/ ECG H- H/K H%( ]%H - Q Oc<b H H: H H# : K %( ]%H K /th ; )" a )" I` % r HF "" = u1: % Z1\H% "HH%H% H% H HIV 1 5Q canalgesicsb H/;v-% /)"## M 0 H/)"H## HG9 O" ) )X cantipyreticsb cimmunomodulatorsb H/_ 9 # H HQ% 961 V f#% 49 )X & ( >"H H% H w % - E % H ; H% B B Di % 5Q E r : )X pv Q ]G% B 6 = "% H caddiction severity index HASIb 6 = " H 5H H _ H5V H H/ :H HF.!'?0C% r : ; OcNb B > = ^ = 1-H% K HL B HX/ ( V B $> "B0!
4 ; % D% ; % ; B C% # Di% ]G9 ; % ; ]HG% )" : : " DHi % ]%H cdhi % s 5d%H = HSb E9 B Gd s $, = 0 /B L B 0 gh gh N H HF% H H HQ 4H9 H H H5: H9 e H5L% H/; ;H s 5d%H = HS OHH% EH9 * ; g ) ; % H9= "H% )9 9e X: 9@1% ; % # ;H / ( B 0 Di% O" "H^ W H H H H5: 9 / B = 1x6 * > )" % B H :H "H % K cs $, S b / H5: /; B? )" )"/% B & %( 2N N XH^ / % ]^ = HS 4H9 OB H > = H^ ;H EH9 ]?.<N CH% )> / % ]^0 s 5d% HX! )X N )>?5V O"% "#I"Q H B HQ H )H> H 2NN NN,' _ H99 H 4H H9 I H/)H> H/H% H,H5% ; 4>-% H*/ HO"H EH9 ", 5x6 2N NX^ )> / O" DQ%<N H( *: < 7 ' /)% H( "HF% H>)" ; B C% O"%( ]6 ELISA 5H H ; H% H )th )" ",9 H 4 )X ]5G9 89 Oc!b " 48 SPSS 600 µg/ml!n "#!)#)!"#C!#(!#" "# "$% & ' ( )*+ %", -$.! 100 µg/ml!n "#!(#* #!# #!# B H 12.5 µg/ml!n "#!)#) B 0g/ml!n!)#( $ % &',-. /01 2 3&'456% 7!8 9$:. 2 ; 2. <=&:0. A 2= D EF G % &' D EFG% IJ4,KG L.MJM% = 5NO. MP Q R = M4$ 3EST 0 "B0! $0
5 -/ )? "(# "() B)+) +*H *#( (#+ +*) H#+H +*) a "# $+ %"$ "# !/ :,R M,EQ. MM$. M0U V4 ""# )B )#+* "+() H#+B H+HC B) *#+) (+*" H# * (#+B "+H) )C H)+" +" "#* ##+( #+ # #( H#+ "+*" H C#+B C+H )( H)+B C+HH )# B *#+B B+(" "##( ##+ C+)C (#H ##+C (+C( C# H+* B+ #+( "#) ##+) "+B B)B )#+* )+#) *)C H)+" +H (# HB B+) #+) H#C C#+" +B "" #+B C+B) H) )#+H H+#" "# H+( B+" #+ )) )#+) +C" )C H)+" )+B) B)B )#+* # (#+* "+B #+" B# "+B #+B( "C( "+ #+C( B#) 0µg/ml XK@ <M S.D. +)µg/ml XK@ <M S.D. ##µg/ml XK@ <M S.D. (##µg/ml XK@ <M?KW OM OM"# OM"# OM"# *&'()%&!"#$a.3+,%2&&µg/ml'(%(/()(0%& -+&,1-&&µg/ml'./0%& -&&,+-.,+µg/ml' (=)> 7(!? (@AB (:5'() ("'$6 78)# 9:5';6<"' 4 )5 )+)H "+) #+(B S.D. ' DE5"$5"C "H H% K C% ; ;-% w?9 H H NW7 C " % K q% % ; H/ "HD,O" )" C% "F% ; H% xd " % K # 7W C uh H% K H = \O" )" D,d% H I )H> V e 5L% /)> X ' # ;% "D W' µg/ml mg/ml 4 )>, " ;D9 D,d% % H% H HX J #H ;H, "D NN 7W< C )" B?S % % ;9u O" ;D9 D,d% c2nn µg/mlb H )> % ;H H"H )"/H% EH9 ;H% "HD B 6 2! U C H% #H ]H?. B H,0 K H HS H$#9 OB H >= H^ 7W CH% H#D ; _ H.D% H H% P ;H H wh% s 5d%H 8 " 8 C% w?9 B C% ID% "0 16 % ' 9 gh HS ; )16O" )"/% E9 ]G% "HF% H DHi% s 5d%H = HS H ;H OB H" HQ # = D C% H% P ;H H w% s 5d% = S H% K _ 5. i Q K " =?6 )> I / Q : ;H " B ; /> O?1 Q K _ 5. i Q K " =?6 5x6 $> K 5> E50 4 = 0 H5: H9 H/;H B? g$9 B,0 OcI"Qb O 5: Systemic b H s H5d%H = S = " H Hd H, "H > A cadverse effects HA01% ]H. s 5d% = j9 OB " % pv HQ H B H" Q ( >)" $_ "B0!
6 ; % D% ; % ; B C% # 89 8 OB >. % ANOVA P P<NWNNb % #D%S V M <J; p<nwnnb C% cf=nnwj % ]F% O cf W< d.f.= d.f.= cf!27wj!w! d.f.= P<NWJ7b C% Q9 C% % ]F% S F "F% ].?1 )> ( % = " )> w% /) : ;# B Q9 % 9"" ]F% S 8 8#%?1 OcF=W! )> 2NN d.f= µg/ml J P<NWN7'b % C% )> ; %( F% B $ #D% C% S )" # * OcF J7WN d.f.= JJ P<NWNNb )" ) ]- I"Q V / "F% )> 49 ( "F% B w% qf /) ; OB )- " I#9 P, pv <N 9 " )"# % <N I"Q /> /} O" V ]% V ( } K / = " "/ % V / O - Z? D,d% % /)> 49 "". /} <N B % A <N 9u?9% N O" )"/% ; % ; ( 7W' _ 99 ( } )> O /)> cx^b } ( "F% # ;, "D / OcN,'b ]. /( H H HQ $Q DQ% % 9 ;H B H )- ; % ; m% Oco7b " Q $Q F%]. fq% ;Hq H9 ; ; ; % ; F% cnb B )" ( S HS ;H OH 5xH6 HQ >"B L * > "#H H. CH% ;9uH )> H#D H 5xH6 H*> % / O" 8 ; %9 O"%( Q )" E9 ; Q U V B 6!J = "% ) e = IH? I 9 pv % <N O"" = HS HQ H #?% > I )% B a> "D ]%H _ H5d% ;H O"H )"/H% H s 5d%H "H HA B HG9 I IV " % H H I "D " % * pv H = Hj9 H> n D,d% % O" )"/% )th H/H ( 8 _? ; % ; H( H/}H I"HQ O" )> / ; % ; B / X <N ; % "i.h phv <N H9 )H B H ; H% fdf% / )> / / ) O"/ % ""% H%O"H )"H H )H> H/ q H% % o]-h H H% IV ( } ;*% H % df $R I"Q OB )" ) <N )"H#/ H H% HdF <?1 X )"#/ K /HO"H B H HQ H B % B H > 48 D?V V )% 9 ( "F% u ; % "i ( /} " "0 ;H, O""H, # "D "F% r L9 ]. ~i ; %"i /( )H> # ;, "D N #D N ;H% "HD CH% H H/ O"H H }H "H )"/% (. } # OH " K # ;% "D /( = "H H wh?9 H aj9 )> / OB Q ( } "F% <N 9 ]^0 h %( = D,d% "B0! $B
7 -/ )? &( "!! )!) ") " # $!!% " "# &' ''"$ = "C = H5 '4 6 #$ G-$F 5 0*&#$ '%2&') =.KL'4 #/IJ2&%&& 4H9 #H B H ;%H 2N "HD 9uH H ( } O " K /)> HQ H* )H> B? )> %( ƒg, H = HX9 <N H, cp<nwnnbb H OB " Q )> ; ( /} ;H #,H %( D,d% h F% ; H% ; I0 9 R ",9 ; % ]^0 D,d%h a, B )" ",9 $Q H%( ]^ 0 D,d%h ; % ; H-/ ;H q H9 ; ; #, ;H HF% B )" ",9 S ; ; B? ; % ; F% = HS H H: H: ]HG9 IH?. ]H. H ;H ;H H wh% s 5d% & -D% ; ; U 1: ; % ; OB " )HH8 IH%/ H# H?5V H/ <N gh H ; H% ; H H HF% ;H# / U C H% H% 9 ]: ",9 e 5L% /; Q=6.KLPO'M$= N7 M H qh9 H >"HQ ;H ; S B H M ; % ; Ocb B > 48 H/ 4H>-% 2NN NN W' H E9 : : ]G9 ; % ;D%,5% IV ; w% ( = S >n/ O H H \ "D )% IV D,d% )% = S O" )"/% " Ij% )% B F % = H0 Q R K ]\% Q e X: ( HQ chd,d% H% H W Z"H0b " 5x6 * > >" E9 ]G% B 0 H/K #H H "HG% C H% ;9uH q HF = 1x H6 H* >OB H HQ H "H )H B C% ;9u /> H-9 s H#9 H% ;H H` H O" )"/% HF% ]H.?1 5Q /)> 49 /P > H/ ( ",9 G9 [ 6 ; % ; O + H( )th H( O" 49 ; % )t H ]. N # ;% ]?. $^ "B0!
8 ; % D% ; % ; B C% # H H6 B H ;H ;H OH% ; ( H*# B H,0 ; % U C% 6 "8% B > H "HF% ;, %*#/ O"#% >5Q HG9 _?H "F% ; % U C% "L% % H "HF% U C H% 9"" ]% 8 "" 6 *# B,0 8 8#% B $ )" )% K / ; ; O% ; % >"##U C% ; H% "F% U C%, = S ;H #D% B DQ O% f. S % H H$Q " "8% B > >5Q, "#/ % I? $Q D% /?, B / ) D% "D9 )" s Q #9 n/ P $#9 ; % ; % # P OB )" #H qhf OB H Hi0 IH0 )"H#/= 8 H H ]H% HVH H "H/:. : ; B y % ] ; O"/ = 8 : % H/ x H9% H$% H> H-/ phv ;H H DX "% X^ O@*y " ^ -/ 5% ;H H H H #H K HL O : 9u /( B? ; % )H>/ H HH( "HF% H H% )"/H%K /H I IV C% / H/ HH( "F% "$* k X0 B $Q ;H )XH H%OB % ; ( #H "HD )H%! "H0 ( / HH( "F% "% A O" % $ g c# ;:( "D )% b )%! "0,?. ]. K / M y co]-b ) K / #,H = HD,d% ]H^0 hh O"/% : #H 4H8 )"H## ;x H9 H )"H##"%,TH% H% H ; H% ;H D% */ )"H 8 ( "F%O"% ; % 6 ;%T9 ; % ; I?. ]. Z? EFG9 ; H ; H% HH( u "F%;# / O% ; % U C% "8%c]%b B > K / ;H O"#% ;%T9 ( ; "% % U CH% H "H8% B H> >H5Q H ; "CH. )H 3H9 H ]H% D% ; % S % " "8% B > >5Q ; H% H "HF% U C H% ")" ; = S ) _ L9 /; % ; % "i ( X Q P:6 XB!:8I$@UC@J#$V W$5STU'6 R- *R.&B O0[ -Z SJ=8K -%33 :6 XB!:8I$@UC@J #$ W$5 ] \X =Z# STU '6 R. -&R.-B O0[ %Z SC K -%1&:8Q P =5$@/X^ #$_ AC 54 5\X=Z#^ $"'$STU'6 R% -&R-1B O0[ -Z SXK -%1&XQ P:6 XB! :8I$@U "B0! "?
9 -/ )? )0-.&& =#$L a U\X=Z#:8C# ^ $"'$STU'6 R` -%1.:8Q P:6 $"#$ 2R..BO0[ %ZSK 5. Akbarzadeh A, Norouzian D, Farahmand B, Nouri Inanlou D. Rapid Latex agglutination inhibition reaction test formorphine in urine. Current Science. 2002; 83 (1): Akbarzadeh A, Mehraby M, Zarbakhsh M, Farzaneh H. Design and synthesis of a morphine-6-succinylbovine serum albumin hapten for vaccine development. Biotechnol Appl Biochem. 1999; 30 (pt 2): Akbarzadeh A, Norouzian D, Farhangi A, Mehrabi MR, Bakhtiari M, Afshar P, et al. Study of human therapeutic morphine vaccine; Safety and Immunogenicity. Asian journal of biochemistry. 2007; 2 (1): Svennerholm AM, Gothefors L, Sack DA, Bardhan PK, Holmgren J. Local and systemic antibody responses and immunological memory after immunization with cholera B subunit by different routes. Bull world Health organ. 1984; 62 (6): Gawin FH, Ellinwood EH. Cocaine and other stimulants: action, abuse and 10. treatment. N Engl J Med 1988; 318 (18) Kosten TR, Rosen M, Bond J, Settles M, Roberts JSC, Shields J, et al. Human therapeutic cocaine vaccine: safety and immunogenicity. Vaccine. 2002; 20 (7): McLellan AT, Kushner H, Metzger D, Peters R, Smith I, Grissom G, et al. The Fifth Edition of the Addiction Severity Index. J Subst Abuse Treat. 1992; 9 (3): Fox BS, Kantak KM, Edwards MA, Black KM, Bollinger BK, Botka AJ, et al. Efficacy of a therapeutic cocainevaccine in rodent models. Nat Med. 1996; 2 (10): Kantak KM, Collins SL, Lipman EG, Bond J, Giovanoni K, Fox BS. Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model. Psychopharmacology (Berl) 2000; 148 (3): Kosten T, Gawin FH, Silverman DG, Fleming J, Compton M, Jatlaw P, et al. Intravenous cocaine challenges during desipramine maintenance. Neuropsychopharmacology 1992; 7 (3): Jaffe JH, Cascella NG, Kumor KM, Sherer MA. Cocaine-induced cocaine craving psychopharmacology (Berl)1989; 97 (1): " "B0!
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