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Efeitos do hormônio de crescimento sobre o metabolismo energético e estresse oxidativo no miocárdio de ratos portadores de insuficiência cardíaca secundária à estenose aórtica

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, / 5 6

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(12)

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(13)

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(14)

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(15)

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5/ k

(16)

7 / – %& 0 "/ "', 3 -', 5 68 /%& ! 0 "'GH 5 68 "%,'GH E 8 0 -0%-*"'GH !% /" *%;-' & ,I(%,8 0 -0%-*"'GH !% B % ;-! 0% !% 3 " &% - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6

Variáveis /

Grupos C - P C - GH EA – P EA - GH

PC

(g) 525,86 ± 61,40 564,04 ± 41,46 477,63 ± 66,17 510,90 ± 33,39b

PCo

(g) 1,28 ± 0,10 1,39 ± 0,15 2,35 ± 0,31a 2,57 ± 0,25b

PCo / PC

(g / kg) 2,47 ± 0,23 2,47 ± 0,18 5,02 ± 1,10a 5,05 ± 0,60b

Proteína

(%) 20,2 ± 1,12 19,1 ± 1,18 18,2 ± 1,04a 16,8 ± 1,29bc

IGF-I

(ng / ml) 1852,39±226,86 2116,16 ±226,48a 837,12 ±211,27a 2108,10 ±689,15c

Índice de Fibrose

(%) 1,88 ± 0,88 1,91 ± 0,74 10,34 ± 1,29a 4,44 ± 1,37 b c

', "%& %7/"%&& & %1 9! ' ^ ) / k L8LV< 5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B 5 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B 506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

0 -0%-*"'GH !% /" *%;-' * *', 5

6 3 "%!$. !' - & '- 1' & ! #"$/

B %1 "%,'GH ' B 5/ k L8 LLD6 % - #"$/

B

%1 "%,'GH ' #"$/

(17)

0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00

C-P C-GH EA-P EA-GH

Grupos

P

C

O

/P

C

0,00 0,50 1,00 1,50 2,00 2,50 3,00

P

C

o

Pco / PC (g /Kg) Peso Coração (g)

#$"' D ` %,'GH %& "'GH 5#6 E %& "/ "', 5F#6 5 E 6 /%, 5#6 !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6< ', "%& %7/"%&& & %1 9! ' ^ 0 1 / l L8LV<

%*"'& 1' I&0$,'& "%/"%&%-*'1 ! 3%"%-G'& %-*"% '""'& % ,%*"'& 1 -I&0$,'& ! 3%"%-G' %-*"% , -+'&< 5 8 '6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

5 8 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

& 0 -0%-*"'GM%& !%

B 3 "'1 1' "%& - & '- 1' & *"'*'! & 0 1

0 1/'"'! 0 1 &%$& "%&/%0* ( & 0 -*" ,%& 5 #$"' =6<

#"$/

B '/"%&%-* $

1%- " 0 -0%-*"'GH !%

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'$1%-* - ;-! 0% !% 3 " &% - #"$/

B 0 1/'"'! 0 1 #"$/ B 5/ k

L8 LLD6 % *"'*'1%-* 0 1

"%!$. $ %&&% ;-! 0% - #"$/

B

0 1/'"'!

' #"$/

B 5/ k L8 LLD6 5 #$"' N6<

(18)

0 500 1000 1500 2000 2500 3000

C-P C-GH EA-P EA-GH

Grupos

n

g

/m

l

#$"' = ` -0%-*"'GH !% B 0 "0$,'-*% - & " !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6<

', "%& %7/"%&& & %1 9! ' ^ 0 1 / l L8LV< %*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% '""'&< 5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B 506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

0 5 10 15

C-P C-GH EA-P EA-GH

Grupos

%

#$"' N ` -! 0% !% 3 " &% 5O6 - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6< ', "%& %7/"%&& & %1

9! ' ^ 0 1 / l L8LV<

%*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% '""'&<

5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

5 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

' %,'

1 &*"' @$% ' '* ( !'!% !' %-. 1'

3 1' & %,%('!'

'/%-'& - #"$/

B

0 1/'"'! 0 1 &%$ 0 -*" ,% 5/ k L8LV6<

& #"$/ &

*"'*'! & 0 1

'/"%&%-*'"'1 %,%('GH -' '* ( !'!% !' %-. 1'

a

a

c

a

(19)

0 1/'"'! 0 1 & 0 -*" ,%& @$% -H "%0% %"'1 *"'*'1%-* < Z ' '* ( !'!% !'

%-. 1' 0 *"'* 0 -*'&% %&*%(% '$1%-*'!' - #"$/ B

8 0 1/'"'!' ' & #"$/ &

B 5/ k L8 LLV6 %

B

5/ k L8LV6<

"%,'GH

E

3 1' " - #"$/ B

0 1/'"'-! 0 1 &%$ #"$/ 0 -*" ,% 5/ k L8 LLD6 % ' "%,'GH

E

%&*%(% '$1%-*'!' - #"$/

B

0 1/'"'!' 0 1 & #"$/ & B

5/ k L8LV6

%

B 5/ k L8LV6<

7 / ` * ( !'!%& !'& %-. 1'& + !" 7 B'0 , 0 %-. 1' !%& !" #%-'&% 5 68 ,'0*'* !%& !" #%-'&% 5 68 0 *"'* & -*'&% 5 6 % '& "%,'GM%& E % E - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6

Variáveis /

Grupos C - P C - GH EA - P EA - GH

OHADH

(nmol / mg proteína) 202,88 ± 23,66 231,76 ± 40,25 220,39 ± 42,15 372,05 ± 147,58

c

LDH

(nmol / mg proteína) 68,42 ± 21,11 119,33 ± 21,28

a

75,30 ± 26,03 105,69 ± 27,56c

CS

(nmol / mg proteína) 167,32 ± 33,32 225,53 ± 37,86

a 146,78 ± 47,33

165,58 ± 39,56b

LDH / CS 0,41 ± 0,11 0,53 ± 0,06a 0,56 ± 0,24 0,65 ± 0,16

OHADH / CS 1,18 ± 0,25 1,02 ± 0,06 1,47 ± 0,52 2,27 ± 0,82bc

', "%& %7/"%&& & %1 9! ' ^ ) / k L8LV< 5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B 5 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B 506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

'

' %,'

%&*H "%/"%&%-*'!'& '& '* ( !'!%& !'& %-. 1'&

(20)

'-* 7 !'-*%& * *' & 5

6<

H 3 "'1 &%"('!'& ! 3%"%-G'& & #- 3 0'-*%& -'&

0 -0%-*"'GM%& !%

% -' "%,'GH

E

- & #"$/ & %&*$!'! &8 %-*"%*'-* '

0 -0%-*"'GH !%

3 1%- " - #"$/

B

0 1/'"'! 0 1 #"$/

B

5/ k L8LLD6<

'* ( !'!% !' %-. 1' 0'*','&% -H 3 ! 3%"%-*% %-*"% & #"$/ &

%&*$!'! &< Z '& '* ( !'!%& !'

%

B 78 @$'-! 0 1/'"'! & & #"$/ &

B %

B

3 "'1 1' & %,%('!'& - #"$/ *"'*'! 0 1

5/ k L8LV % / k L8

LLV8 "%&/%0* ('1%-*%68 % 1' & %,%('!'& *'1 91 %1 "%,'GH ' #"$/ B

5/ k

L8LV6<

'* ( !'!% !' %-. 1'

%&*%(% '$1%-*'!' - #"$/

B 0 1/'"'!

0 1 B 5/ k L8LV6 5 #< >6<

'* ( !'!% !'

B ! 3 1%- " - #"$/

B

0 1/'"'! 0 1 B

5/ k L8 LLV6 %

B 5/ k L8LV6< & "%,'GM%& !'&

%-. 1'& '-* 7 !'-*%& 0'*','&% E

8

E

%

B 7 E

&H 1 &*"'!'&

-'

#$"' V< /%-'& #"$/

B

8 0 1/'"'! 0 1 #"$/

B 8 '/"%&%-* $

%,%('GH -%&*'& "%,'GM%&<

& &*%1' #,$*'* -' %&* "%/"%&%-*'! -'&

#$"'& K % R<

0 -0%-*"'GH

!% #,$*'* -' 7 !'!' 5

6 %&*%(% 1' & %,%('!' - & #"$/ & B

5/ k L8LV6 %

B

5/ k L8LV68 0 1/'"'! & ' #"$/

B

% ! 1 -$ $ - #"$/

B

0 1/'"'! ' &%$ #"$/ 0 -*" ,% 5/ k L8LV6<

0 -0%-*"'GH !' #,$*'* -'

"%!$. !' 5

6 3 1%- " - & #"$/ & 0 1 %&*%- &%8 0 1/'"'! & ' & &%$&

"%&/%0* ( & 0 -*" ,%&< Z ' "%,'GH

E

3 1%- " '/%-'& - & #"$/ & B

(21)

7 / )`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

Variáveis / Grupos C - P C - GH EA - P EA – GH

HP

(nmol / mg tecido) 193,77 ± 54,73 162,49 ± 103,19 169,47 ± 44,19 99,08 ± 45,23

c

SAT (%) 31,24 ± 5,66 37,17 ± 16,59 30,30 ± 6,16 34,56 ± 9,15

HP / SAT 6,33 ± 1,86 6,06 ± 5,12 6,05 ± 2,85 3,30 ± 2,26

Catalase

(nmol/ mg proteína) 1,23 ± 0,13 1,32 ± 0,18 1,27 ± 0,15 1,47 ± 0,27

SOD

(nmol/ mg proteína) 7,34 ± 0,57 7,67 ± 0,55 8,36 ± 1,36

a

10,02 ± 1,70bc

GSH-Px

(nmol/ mg proteína) 47,70 ± 17,58 39,70 ± 16,62 35,40 ± 17,20 60,93 ± 5,21

bc

GSH-Rd (nmol/ mg proteína)

2,57 ± 1,35 1,46 ± 0,07 2,65 ± 1,35 1,13 ± 0,15bc

GSSG

(nmol / mg tecido) 0,68 ± 0,14 1,32 ± 0,45

a

0,92 ± 0,36a 0,86 ± 0,11b

GSH

(nmol / mg tecido) 12,32 ± 1,13 12,70 ± 1,07 10,26 ± 1,52

a

10,99 ± 0,41b

GSH / GSSG 19,04 ± 5,05 10,46 ± 3,29a 12,02 ± 2,97a 12,85 ± 1,43

Catalase / HP 6,53 ± 1,66 9,39 ± 5,27 7,54 ± 2,13 12,54 ± 4,93c

SOD / HP 8,07 ± 2,48 11,95 ± 7,94 9,05 ± 2,68 14,22 ± 6,64c

GSH-Px / HP 444,51 ±274,97 699,85 ± 511,97 365,32 ± 167,37 902,43±466,13c

(22)

0 2 4 6 8 10 12 14

C-P C-GH EA-P EA-GH

Grupos S O D ( n m o l/ m g p ro t) 0 10 20 30 40 50 60 70 G S H -P x (n m o l/ m g p ro t) SOD GSH-Px

#$"' > ` * ( !'!% !'& %-. 1'& '-* 7 !'-*%& 5-1 , E 1# /" *%;-'6 &$/%"C7 ! ! &1$*'&% 5 6 % #,$*'* -' /%" 7 !'&% 5 B 6 - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6< ', "%& %7/"%&& & %1 9! ' ^ 0 1 / l L8LV<

%*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% , -+'&<

5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

5 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

a

(23)

0

5

10

15

20

25

C-P

C-GH

EA-P

EA-GH

Grupos

E

n

z

im

a

/

H

P

Catalse / HP

SOD / HP

GSH-Px / HP*

#$"' V ` %,'GM%& %-*"% 0'*','&% E + !" /%"C7 ! !% , /;! 5 68 &$/%"C7 ! ! &1$*'&% 5 6 E % #,$*'* -' /%" 7 !'&% 5 B 76 E m - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6<

', "%& %7/"%&& & %1 9! ' ^ 0 1 / l L8LV< %*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% '""'&< 506 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B <

*A relação GSH-Px / HP está dividida por 100.

0,0 2,0 4,0 6,0 8,0 10,0 12,0 14,0 16,0

C-P C-GH EA-P EA-GH

Grupos G S H ( n m o l/ m g t e c ) 0,0 0,5 1,0 1,5 2,0 G S S G (n m o l/ m g t e c ) GSH GSSG

#$"' K ` -0%-*"'GH !% #,$*'* -' "%!$. !' 5 6 % #,$*'* -' 7 !'!' 5 68 %1 -1 ,E1# *%0 ! 8 - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6< ', "%& %7/"%&& & %1 9! ' ^ 0 1 / l L8LV<

%*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% , -+'&<

5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

5 6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

c

c

c

a

a

b

(24)

0,0

5,0

10,0

15,0

20,0

25,0

30,0

C-P

C-GH

EA-P

EA-GH

Grupos

#$"' R ` %,'GH %-*"% 0 -0%-*"'GH !% #,$*'* -' "%!$. !' 5 6 % #,$*'* -' 7 !'!' 5 68 - 1 0 "! !% "'* & 0 -*" ,%& 5 B 68 *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 68 &$ 1%* ! & X %&*%- &% 'C"* 0' 5 B 6 % &$ 1%* ! & X %&*%- &% 'C"* 0' *"'*'! & 0 1 + "14- !% 0"%&0 1%-* 5 B 6< ', "%& %7/"%&& & %1

9! ' ^ 0 1 / l L8LV<

%*"'& 1 -I&0$,'& "%/"%&%-*'1 ! 3%"%-G' %-*"% '""'&< 5'6 3%"%-G' & #- 3 0'-*% %1 "%,'GH ' #"$/ B

Discussão

%&!% /" 1% " *"' ',+ 3% * / " $0+'"!8 %1 DJTV8 1 &*"'-! ' "%,'GH %-*"% & &*%1' 0'"! ('&0$,'" % 8 ( " & /%&@$ &'! "%& (:1 %&*$!'-! ' 'GH !%&&% + "14- %1 /" ,%1'& 0'"!;'0 &< 1 "' 2 %&*%2' 0,'"' ' -*%"'GH % 0 "'GH 8 & "%&$,*'! & /'"' *"'*'1%-* !% 0'"! /'* '& 0 1 + "14- !% 0"%&0 1%-* &H 0 -3, *'-*%& 5 YB =LLR6< ,#$-& *"' ',+ & '/ -*'1 /'"' $1'

1%,+ "' !' 3$-GH 0'"!;'0' 5P DJJN) YY DJJK)

DJJR) =LLL6 %-@$'-* $*" & *"' ',+ & -H %-0 -*"'"'1 %3% * & %-93 0 & - 0 "'GH '/C& *"'*'1%-* 0 1 5 Y DJJT)

=LLN6< %(%B&%8 %-*"%*'-* 8 - *'" @$% 1' " /" ,%1' %1 "%,'GH X %&* !$"'-*% "%', .'GH !% %7%"0;0 & 3;& 0 & 5? DJT>) ? DJT= 8 @$% 3 #% ! & 2%* ( & !%&*% %&*$! <

(25)

1 "' +'2' #"'-!% -I1%" !% *"' ',+ & 1 &*"'-! ' 1/ "*S-0 ' ! /'"' 0 "'GH % 1$ * & ' -!' -! @$%1 $1 %3% * *%"'/:$* 0 -' 8 / $0 &% &' % & "% ' -3,$:-0 ' !%&&% + "14- -' '* ( !'!% !% %-. 1'& 1'"0'! "'& ! 1%*' , &1 %-%"#9* 0 ! 0 "'GH 0 1 8 &%0$-! " ' X %&*%- &% 'C"* 0'< %&*' 3 "1' %&*% *"' ',+ 2%* ( $ (%" 3 0'" & %3% * & 1%*' C, 0 & % "%,'0 -'! & 0 1 - *"'*'1%-* 0 1 ' ! &% !% D1#EF# !% %1 "'* & 0 1 &%0$-! " ' X %&*%- &% 'C"* 0'<

*"'*'1%-* 0 1 & ,'! -H '$1%-* $ #'-+ !% 8 &%1%,+'-*% ' $*" &

*"' ',+ & 5 Z DJJJ) =LLN6< 1 "' &%2' $1

+ "14- '-' C, 0 8 ' ! &% $* , .'!' -%&*% *"' ',+ 9 0 -& !%"'!' ' 7'< "' ',+ & 0 1 ! &%& 1' & ',*'& %-0 -*"'"'1 '$1%-* & #- 3 0'-*% - 5 =LLD)

DJJJ) DJJT) DJJK6< & '- 1' & ! #"$/

B * (%"'1 $1' "%!$GH ! &%$ 3 -', %1 "' -H *%-+' & ! %&*'* &* 0'1%-*% & #- 3 0'-*%< && &% !%$ /%, ',* !%&( /'!"H !%&*' ('" (%,< ! & & '- 1' & 0 1 3 "'1 '#"$/'! & !% '0 "! 0 1 '& ('" (% & %0 0'"! #" 3 0'&8 %1 #"'(% 5 =LLK68 %-*"%*'-* 8 %"'1 '&*'-*% +%*%" #:-% & %1 "%,'GH X !'!%8 %7/, 0'-! '&& 18 %,%('! !%&( /'!"H < f$'-! '-', &'! & & '- 1' & ! #"$/

B 9 / &&;(%, - *'" %3% * !' -' "%!$GH ! /%& 0 "/ "',<

*"'*'1%-* 0 1 -H %,%( $ %1 0 1 ' "%,'GH E - & '- 1' & 0 -*" ,% % 0 1 8 %1 '0 "! 0 1 $*" & '$* "%& 5P DJJN) W

DJJT) Z DJJJ68 1 &*"'-! @$% 8 -%&*' ! &%8 -H 0'$& $ + /%"*" 3 ' 0'"!;'0' &%-! 8 / "*'-* 8 $1' ! &% &%#$"'< Z & #"$/ & 0 1 '/"%&%-*'"'1 '$1%-* - % -' "%,'GH E 8 %( !%-0 '-! $1' / &&;(%, "%&/ &*' + /%"*"C3 0' 0'"!;'0' 5 DJJR) W DJJT6 0'$&'!' /%,' %&*%- &%8 % @$% -H 3 '#"'('!' /%, *"'*'1%-* 0 1 <

(26)

!' /" !$GH '$1%-*'!' !% B 8 - & '- 1' & @$% "%0% %"'1 *"'*'1%-* < 0 -0%-*"'GH ! 1 -$;!' !% B - & '- 1' & 0 1 &$/M% $1' / &&;(%, "%& &*:-0 ' X 'GH ! -' 8 %1 '0 "! 0 1 $*" & *"' ',+ & 5 DJJR6< 1' (%. @$% B 9 $1 %3%* " 1/ "*'-*% !'& 'GM%& ! 8 %&&' "%!$GH %7/, 0'8 ' 1%- & %1 /'"*%8 '& ',*%"'GM%& - #"$/ B <

'@$%7 '8 @$% 1$ *'& (%.%& '0 1/'-+' ' 5 DJRK68 9 $1 %&*'! - @$', 0 ""% ',* #"'$ !% 0'*' , &1 8 0 1 !%/,%GH !'& "%&%"('& /" *9 0'& % /%"!' !% /%& 5 W DJJR6< 1 "' & "%&$,*'! & -H /%"1 *'1 '3 "1'" %&&% !%&%@$ ,; " %-*"% '-' , &1 % 0'*' , &1 8 %&&% 3'* / !%" ' %7/, 0'" ' "%!$GH !'

/ "0%-*'#%1 !% /" *%;-' - #"$/ B 5 DJJV) DJJR6<

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

3 " &% 1 0 "! 0' 9 0 -& !%"'!' $1 !%*%"1 -'-*% ,C# 0 '&& 0 '! 0 1 $1

1'$ /" #-C&* 0 -' 5 DJTJ) =LLN6< $1%-*

-' 0 -0%-*"'GH !% 0 , #%- - 0 "'GH 3 !%1 -&*"'! %1 ( " & 1 !%, & !%

+ /%"*" 3 ' 0'"!;'0' 5 DJTT) DJTL)

(27)

',#$-& *"' ',+ & %,%( $ /%& ! 0 "'GH &%1 ,%('" ' $1 '$1%-* & #- 3 0'-*%

-' 3 " &% 1 0 "! 0' 5 DJJK) DJJK6< ,#$1'&

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

1 "' ' %&*%- &% ! -H *%-+' ',*%"'! '& %-. 1'& 1'"0'! "'& ! 1%*' , &1 0'"!;'0 '-', &'!'& -%&*% %&*$! 8 *"'*'1%-* 0 1 %,%( $ '& '* ( !'!%& %-. 1 * 0'& &%1%,+'-*%1%-*% ' #"$/ B <

#"$/ B '/"%&%-* $ %,%('GH -'& '* ( !'!%& !' %-. 1' % 8 1'"0'! "'& ! 1%*' , &1 '-'%"C 0 % '%"C 0 8 "%&/%0* ('1%-*%< %#$-! *' -& c Q " F& 5DJJL6 ',*'& 0 -0%-*"'GM%& !% ,'0*'* 3 "1'!'& - 0 * & ,8 %1 &;* & ! &*'-*%& !'& 1 * 04-!" '&8 &H ,%('! & ' &;* & /"C7 1 & !%&&'& "#'-%,'& / " ! 3%"%-G' !% 0 -0%-*"'GH < &&% %70%&& !% ,'0*'* 9 7 !'! ' / "$('* 8 1'-*%-! 0 -&*'-*% ' "%,'GH E i /'"' ' 1'-$*%-GH !'& "%'GM%& 0%,$,'"%& 1 * 0 -!" ' & 5( '

(28)

1' + /C*%&% ',*%"-'* (' 9 !%&( -*"'0%,$,'" ! ,'0*'* /" / &* / " ,'!!%-5=LLD6 5 &@$%1' 68 -' @$', ,'0*'* /" !$. ! - 0 * & ,8 /%,' '* ( !'!% !% $1' & %-. 1' !' 8 %-*"' -' 1 * 04-!" ' ! "%*'1%-*% % %-*H 9 7 !'! - ('1%-*% ' / "$('* 8 %-*"'-! '&& 1 - 0 0, !% W"% &8 #%"'-! & %@$ (',%-*%& "%!$* "%& /'"' '& "%'GM%& /" !$* "'& !% %-%"# '< 1 '& '& + /C*%&%& %7/, 0'1 '$1%-* !'& '* ( !'!%& !' % -!$. !'& /%, <

#"$/ % @$% "%0% %$ '/"%&%-* $ %,%('GH -'& '* ( !'!%& !' % jB % "%!$GH -' '* ( !'!% !' %-. 1' 1'"0'! "' ! 1%*' , &1 '%"C 0 8 <

(29)

' %B&% @$% ' 7 !'GH !% & ,%(' ' $1' 1' " /" !$GH !% 0 *"'* % %&&% 9 $1 - ! " ', &*9" 0 !' %-. 1' 3 &3 3"$* F -'&% 5 WBD68 !%&*' 3 "1' "%!$. -! ' (%, 0 !'!% !' ( ' #, 0 ,;* 0'8 / "*'-* 1%- & / "$('* %&*'" ' &%-! 3 "1'! ( ' #, 0C, &%< $1%-* -' ! &/ - , !'!% !% , /;! & *'1 91 %,%(' ' '* ( !'!% !' %-. 1' / "$('* !%& !" #%-'&% 5 6 @$ -'&%8 @$% / " &$' (%. 3 &3 " ,' 0 1/,%7 8

* "-'-! B -'* ( 5 Z % B Y8 =LL=6) !%&*' 1'-% "'

/ "$('* 3 "1'! -' ( ' #, 0 ,;* 0' 9 !%&( '! /'"' ' "%!$GH '*9 ,'0*'* 8 %7/, 0'-! '$1%-* !' '* ( !'!% !' ' /'"* " ! '$1%-* !' 7 !'GH !% , /;! &<

"%!$GH !' '* ( !'!% !' %-. 1' - #"$/ B / !% *%" & ! 0'$&'!' /%,' ' 7' 0 -0%-*"'GH !% 7 #:- @$% 0+%#' '*9 0 "'GH 0 1 < /" !$GH !% %-%"# ' -' 0'!% ' *"'-&/ "*'! "' !% %,9*" -& 9 '&*'-*% &%-&;(%, ' ',*%"'GM%& -'& 0 -0%-*"'GM%& !% =8 !%&*' 3 "1' 0 -! GM%& !% + /C7 ' ! 1 -$ " '1 ' '* ( !'!% !' 8 "%!$. -!

'&& 1 ' /" !$GH !% %-%"# ' ( ' 1%*' , &1 '%"C 0 < 1' (%. @$% 9 $1 + "14- 0 1 '* ( !'!% '-' C, 0'8 &* 98 /" 1 (% "%'GM%& @$% -%0%&& *'1 !% %-%"# '8 % %&&' %-%"# ' "%@$%" &$/" 1%-* !% = '!%@$'! 8 ' "%!$GH -' '* ( !'!% !'

(30)

*:1 '/ -*'! /'"' & %3% * & %-%"#9* 0 & %-93 0 & !' /" !$GH !% ,'0*'* % / "$('* - 0 "'GH 5 8 =LL>) =LLV68 !%&*' 3 "1' 8 0 "" "'-! 0 1 %&*%& *"' ',+ &8 ,%('" ' ' %3% * & %-93 0 & %1 "%,'GH ' 1%*' , &1 %-%"#9* 0 0'"!;'0 <

1 "' & %3% * & 1%*' C, 0 & 0'$&'! & /%, '$1%-* !' 7 !'GH !% 0 ! & #"'7 & -H *%-+' /"%2$! 0'! ' /" !$GH !% %-%"# ' 1 0 "! 0'8 $1' !'& 0 -&%@U:-0 '& ! '$1%-* !' jB 7 !'GH 9 ' 3 "1'GH -! "%*' !% *" '0 ,#, 0%" ,< 1 0 -! GM%& !% &@$%1 ' + $1' ! 1 -$ GH !' '* ( !'!% !' %-. 1' 8 !%&*' 3 "1' 1%- & '0%* ,B 9 7 !'! - 0 0, ! 0 *"'* < %70%&& !%&*% -*%"1%! " " $-! *'-* !' ( ' #, 0 ,;* 0'8 0 1 !' jB 7 !'GH 9 !%( ,( ! ' 0 * & ,8 3 "1'-! 1', - ,B 8 @$% / " &$' (%. - % ' '* ( !'!% !' %-. 1' 0'"- * -'B'0 ,B*"'-&3%"'&% D 5 BD68 "%&/ -& (%, /%,' %-*"'!' !% '0 ,B 3 "1'! ' /'"* " ! & &< %&*' 3 "1' + $1 1%0'- &1 !% 3%%! '0F -%#'* ( @$% %,%(' ' 3 "1'GH !% *" '0 ,#, 0%" , 1 0 "! 0 8 &%-! $1 &$ &*"'* ',*'1%-*% &$&0%/*;(%, ' '*'@$% /%, & & 5 &@$%1' 6< %&*% *"' ',+ -H 3 "'1 @$'-* 3 0'!'& '& 0 -0%-*"'GM%& !% *" '0 ,#, 0%" , 1 0 "! 0 <

8 -%&*% %&*$! 8 '/"%&%-* $ %3% * & %-93 0 & %1 "%,'GH ' & /'"S1%*" & 7 !'* ( & ! 0 "'GH 0 1 %&*%- &% 'C"* 0'<

(31)

1 "' #"$/ B *'1 91 -H *%-+' '/"%&%-*'! %,%('GH ! 8 % E 8 -%&*% #"$/ 0 ""%$ "%!$GH -' "%,'GH E 8 *'-* /%, '$1%-* !'

0 1 /%,' ! 1 -$ GH !' < "%,'GH ! 1 -$;!' E 5 Y

DJJJ68 '&& 0 '!' 0 1 ' %,%('GH !' %-. 1' '-* 7 !'-*% 8 -! 0' $1 !'- 1' " 0'$&'! /%, & &8 !%( ! ' < 1 "' *%-+' 0 "" ! '$1%-* - - #"$/ B 8 %1 '0 "! 0 1 $*" & *"' ',+ & 5 DJJD) 0 P

"# W DJJT68 ' 1'-$*%-GH - & -;(% & !% / !% &%" !%0 ""%-*% !'

/" *%GH 0'$&'!' /%, '$1%-* '!'/*'* ( 5 Q W 8 DJJL6 !'

'* ( !'!% !' %-. 1' < &*' %-. 1' /" 1 (% ' ! &1$*'GH ! =B'*9 = =8 %( *'-!

& !'- & 0'$&'! & / " %&&% < Z ' /" !$GH !% = =9 -%$*"', .'!' /%, & &*%1' !'&

(32)

%&*% %&*$! 8 - #"$/ B -H + $(% ',*%"'GH !'& %-. 1'& B % B !8 1 &*"'-! @$% = =3 -%$*"', .'! /%,' 'GH ! "%*' !' <

#"$/ 0 1 @$% "%0% %$ *"'*'1%-* 0 1 *%(% "%!$GH - & -;(% & !% 8 '/ -*'-! /'"' %3% * /" *%* " ! < &&' "%!$GH %&* '&& 0 '!' 0 1 '$1%-* !'& "%,'GM%& E 8 0'*','&%E % B 7E 8 1 &*"'-! %3% * "%!$* " !% ! < %#$-! *% .' 5DJJR6 ' "%,'GH %-*"% & & &*%1'& '-* 7 !'-*%&E 7 !'-*% !%(% &%" 0 -& !%"'!' 0 1 &%-! 1' & "%/"%&%-*'* (' @$% (', " ' & ,$* !'& '* ( !'!%& %-. 1 * 0'&8 %1 "' -%&*% %&*$! '& '* ( !'!%& ' & ,$*'& !'& %-. 1'& &$/%"C7 ! ! &1$*'&% % #,$*'* -' /%" 7 !'&% *'1 91 *%-+'1 '$1%-*'! - #"$/ *"'*'! % 0 1 < '* ( !'!% '$1%-*'!' !' - #"$/ B 0 1/'"'!' 0 1 #"$/ B / !% %&*'" "%,'0 -'!' 0 1 '$1%-* !' /" !$GH !%

=B0'$&'! /%, 5 DJJK 8 !%&*' 3 "1'8 0 "'GH -%0%&& *'" ' !% $1'

1' " /" *%GH /'"' %( *'" & %3% * & - 0 ( & !%&*% <

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