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V=5B8G=89 D5@<5=B0B82=89 <5B>4, @50:FVO >?8A0=0 "0;:5 V (C15@B><,24>A:>=0;5=0 7 C@0EC20==O< ?@>?>@FV9=>ABV 7<V=8 01A>@1FVW 2 >48=8FN G0AC. !:;04 @5035=BV2: R1 "@VA-1CD5@ 100 <<>;L/; -:5B>3;CB0@0B 5,49 <<>;L/; #@5070 e" 10 :4/<;  e" 3,8 :4/<; R2  1,66 <<>;L/; "0:>6 <VAB8BL @50:FV9=>-=59B@0;L=V =0?>2=N20GV V AB01V;V70B>@8 >5DVFVT=B ?5@5@0EC=:C <<>;L/; = 0,1665 E <3/4; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 11,5 <3/4; (1,91 <<>;L/;) V=V9=VABL: 4> 300 <3/4; (49,8 <<>;L/;) (A5G>28=0) 4> 140 <3/4; (23,24 <<>;L/;) (07>B A5G>28=8) V0?07>= 28<V@N20==O: 11,5 300 <3/4; (1,91 23,24 <<>;L/;) #<>28 715@V30==O 2V4 +2 4> +8 C. !2 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 5035=B ?@87=0G5=89 4;O in vitro 287=0G5==O 0:B82=>ABV 0;LD0-0<V;078 C A8@>20BFV V ?;07<V :@>2V, 0 B0:>6 A5GV ;N48=8 2?0: $0AC20==O: 5035=B 1 =5 <5=H5 5 x 22 <; ;LD0-0<V;070 2 >@30=V7<V ;N48=8 <>65 <0B8 @V7=5 ?>E>465==O: ?0=:@50B8G=00<V;070 A8=B57CTBLAO ?V4H;C=:>2>N 70;>7>N V 28E>48BL C :8H:>289 B@0:B, A;8==0 0<V;070 A8=B57CTBLAO C A;8==8E 70;>70E V A5:@5BCTBLAO 2 A;8=C.;LD0-0<V;070 :0B0;V7CT 3V4@>;V7 -1-4-3;V:>784=8E 72 O7:V2 :@>E<0;N B0 V=H8E A?>@V4=5=8E ?>;VA0E0@84V2 06 4> <0;LB>78 B0 V=H8E >;V3>A0E0@84V2. $5@<5=B0;LD0-0<V;070 - ?>@V2=O=> =525;8:0 <>;5:C;0, I> H284:> 282>48BLAO =8@:0<8 B0 2840;OTBLAO V7 A5G5N. !:;04 @5035=BV2: 5035=B 1 MES-1CD5@ 50 <<>;L/; 0;LFVN E;>@84 3,81 <<>;L/; 0B@VN E;>@84 300 <<>;L/; 0;VN BV>FV0=0B 450 <<>;L/; CNP-G 0,91 <<>;L/; 0B@VN 0784 13,85 <<>;L/; >5DVFVT=B ?5@5@0EC=:C 4/; E 0,017 = <::0B/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 10,8 4/; V=V9=VABL: 4> 1500 4/; V0?07>= 28<V@N20==O: 10,8 1500 4/; #<>28 715@V30==O 2V4 +2 4> +8 C. !3 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 5035=B ?@87=0G5=89 4;O 4V03=>AB8:8 in vitro ALT (0;0=V=0<V=>-B@0=AD5@078) 2 A8@>20BFV :@>2V B0 ?;07<V 2?0: $0AC20==O: R1: =5 <5=H6 x 44 <;, R2: =5 <5=H6 x 11 <;. "/"  T =09206;82VH8<8 ?@54AB02=8:0<8 0<V=>B@0=AD5@, O:V :0B0;V7CNBL ?5@5B2>@5==O 0-:5B>BVA;>B0 2 0<V=>:8A;>B8, ?5@5=>AOG8 0<V=>:8A;>B8. ALT ?@8ACB=V9 C 28A>:8E :>=F5=B@0FVOE 2 ?5GV=FV, 2 =87L:8E :>=F5=B@0FVOE 2 =8@:0E, A5@F52V9 V A:5;5B=V9 B:0=8=V <&apos;O7V2, ?V4H;C=:>2>W 70;>78, A5;57V=:8 V ;535=V2. !:;04 @5035=BV2: R1 "@VA 1CD5@ (pH 7,5) 137,5 <<>;L/; L-;0=V= 709 <<>;L/;  (<V:@>1=0) e" 2000 /; R2 CAPSO 20 <<>;L/; 2-:A>3;CB0@0B 85 <<>;L/;  1,05 <<>;L/; >5DVFVT=B ?5@5@0EC=:C /; E 0,017 = <::0B/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 4,43/4; V=V9=VABL: 4> 3603/4; V0?07>= 28<V@N20==O: 4,4 3603/4; #<>28 715@V30==O 2V4 +2 4> +8 C. !4 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 5035=B8 ?@87=0G5=V 4;O :V;L:VA=>3> in vitro 287=0G5==O 0A?0@B0B0<V=>B@0=AD5@078 (A!") C A8@>20BFV V ?;07<V :@>2V ;N48=8. 3?0: $0AC20==O: R1: =5 <5=H56 x 44 <;, R2: =5 <5=H56 x 11 <;. 091V;LH 206;82V ?@54AB02=8:8 0<V=>B@0=AD5@07, I> :0B0;V7CNBL ?5@5B2>@5==O 0-:5B>:8A;>B =0 0<V=>:8A;>B8 H;OE>< ?5@5=>AC0<V=>3@C?.A!" <VAB8BLAO C 2AVE B:0=8=0E ;N48=8, ?>@V2=O=> 28A>:89 @V25=LA?>AB5@V30TBLAO 2 A5@FV, ?5GV=FV, =8@:0E, A:5;5B=8E < O7>28E B:0=8=0EV 5@8B@>F8B0E :@>2V. !:;04 @5035=BV2: "@VA-1CD5@ (pH 7,8) 110 <<>;L/; L-0A?0@B0B 340 <<>;L/;  e" 4000 4/;  e" 750 4/; R2 CAPSO 20 <<>;L/; 2->:A>3;CB0@0B 85 <<>;L/;  1,05 <<>;L/; >5DVFVT=B ?5@5@0EC=:C 4/; E 0,017 = <::0B/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 3,84 4/; (0,064 <::0B/;) V=V9=VABL: 390 4/; (6,5 <::0B/;) V0?07>= 28<V@N20==O: 3,84  390 4/; (0,064  6,5 <::0B/;) #<>28 715@V30==O 2V4 +2 4> +8 C. ! 5 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 01V@ @5035=BV2 ?@87=0G5=89 4;O :V;L:VA=>3> invitro 287=0G5==O 30<<0-3;CB0<V;B@0=AD5@078 (", GGT) C A8@>20BFV V ?;07<V :@>2V ;N48=8. 8?0: $0AC20==O: =5 <5=H5R1: 2 x 44 <;, R2: 2 x 11 <; 87=0G5==O " T :;V=VG=> 206;828< 4;O 28O2;5==O >1AB@C:FVW 6>2G=8E?@>B>:V2, 4V03=>AB8:8 2V@CA=>3> 35?0B8BC (3>AB@>3> V E@>=VG=>3>) V E>;5F8AB8BC. 8A>:V 7=0G5==O B0:>6 A?>AB5@V30NBLAO ?@8 26820==V =0@:>B8G=8E 70A>1V2,0;:>3>;L=8E =0?>W2, 70A?>:V9;828E V ?@>B8AC4><=8E 70A>1V2, 0 B0:>6 "@0=:2V;V70B>@V2. !:;04 @5035=BV2: R1 "@VA-1CD5@ (pH - 8,25) 125 <<>;L/; ;VF8;3;VF8= 125 <<>;L /; R2 L--3;CB0<V;-3-0@1>:AV-4-=VB@>0=V;V4 20 <<>;L /; >5DVFVT=B ?5@5@0EC=:C 4/; E 0,017 = <::0B/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 1,68 4/; V=V9=VABL: 4> 500 4/; V0?07>= 28<V@N20==O: 1,68 500 4/; #<>28 715@V30==O 2V4 +2 4> +8 C. !6 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 5035=B ?@87=0G5=89 4;O :V;L:VA=>3> in vitro 287=0G5==O B@83;VF5@84V2 C A8@>20BFV V ?;07<V :@>2V ;N48=8. 2?0: $0AC20==O:=5 <5=H5R1: 10 x 44 <;. "@83;VF5@848  5B5@8 68@=8E :8A;>B V 3;VF5@8=C. 87=0G5==O @V2=O B@83;VF5@84V2 T 206;828< 4;O 287=0G5==O 3V?5@;V?>?@>B5V45<V9. V?5@;V?>?@>B5W45<VW ?>4V;ONBLAO =0 ?5@28==V (A?04:>2V) V2B>@8==V: >68@V==O,FC:@>289 4V015B, =5D@>B8G=89 A8=4@><, 5=4>:@8==V E2>@>18, ?0=:@50B8B.V428I5==O :>=F5=B@0FVW B@83;VF5@84V2 B0:>6 2:07CT =0 @878:8 A5@F52>-AC48==8E 70E2>@N20=L. !:;04 @5035=BV2: R1 Hood s 1CD5@ (@ 7,2) 50 <<>;L/; 4-E;>@D5=>; 4 <<>;L/; Mg 2+ 15 <<>;L/; AT$ 2 <<>;L/; ;VF5@>;:V=070 e" 0,4 :4/; 5@>:A84070 e" 2 :4/; V?>?@>B5W=;V?070 e" 2 :4/; ;VF5@>;-3-D>AD0B>:A84070 e" 0,5 :4/; 4-0<V=>0=B8?V@8= 0,5 <<>;L/; >5DVFVT=B ?5@5@0EC=:C (<3/4;) E 0,0113 = <<>;L/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 9,74 <3/4; (0,11 <<>;L/;) V=V9=VABL: 4> 1062 <3/4; (12 <<>;L/;) V0?07>= 28<V@N20==O: 9,74 1062 <3/4; (0,11 12 <<>;L/;) #<>28 715@V30==O 2V4 +2 4> +8 C. !7 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 5035=B ?@87=0G5=89 4;O :V;L:VA=>3> in vitro 287=0G5==O 3;N:>78 2 A8@>20BFV V ?;07<V :@>2V, 0 B0:>6 C A5GV ;N48=8. 2?0: $0AC20==O:=5 <5=H5R1: 10 x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in vitro 287=0G5==O 7030;L=>3> 1V;:C C A8@>20BFV V ?;07<V :@>2V ;N48=8. 1?0: $0AC20==O: =5 <5=H5 1: 10E44 <;. V;:8 V ?5?B848 2 ;C6=><C A5@54>28IV CB2>@NNBL 7 V>=0<8 <V4V () :><?;5:A A8=L>-DV>;5B>2>3> :>;L>@C. 0;V9-=0B@V9 B0@B@0B 4>40TBLAO C O:>ABV AB01V;V70B>@0, 9>484 :0;VN - 4;O 70?>1V30==O @>7:;04C CB2>@5=>3> :><?;5:AC. !:;04 @5035=BV2: 1 V4V AC;LD0B (I) 12 <<>;L/;, 0;VN-=0B@VN B0@B@0B 31,9 <<>;L/;, 0;VN 9>484 30,1 <<>;L/;, 0B@VN 3V4@>:A84 0,6 <>;L/;. #<>28 715@V30==O 2V4 +2 4> +8 C. >5DVFVT=B ?5@5@0EC=:C (3/4;) E 10 = 3/;. >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 0,37 3/4; (3,7 3/;) V=V9=VABL: 4> 15 3/4; (150 3/;) V0?07>= 28<V@N20==O: 0,37-15 3/4; (3,7-150 3/;). !9 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 01V@ @5035=BV2 ?@87=0G5=89 4;O :V;L:VA=>3> in vitro 287=0G5==O 2<VABC 70;V70 C A8@>20BFV V ?;07<V :@>2V ;N48=8. $>B><5B@8G=89 B5AB V7 28:>@8AB0==O< E@><>35=C D5@@>78=C. 2?0: $0AC20==O: =5 <5=H5 R1: 4 x 25 <;, R2: 4 x 6,5 <;, R3 AB0=40@B: 1 E 4 <; >=8 B@820;5=B=>3> 70;V70 282V;L=NNBLAO 7 :><?;5:AC 70;V7>-B@0=AD5@8= A8@>20B:8 :@>2V V 2V4=>2;NNBLAO ?V4 4VTN :8A;>3> @>1>G>3> @>7G8=C, O:89 <VAB8BL 2V4=>2=8: (3V4@>:A8;0<V=C 3V4@>E;>@84), 4> V>=V2 42>20;5=B=>3> 70;V70. VA;O 4>4020==O D5@@>78=C CB2>@NTBLAO ABV9:89 7010@2;5=89 :><?;5:A DV>;5B>2>3> :>;L>@C. =B5=A82=VABL 9>3> 7010@2;5==O T ?@>?>@FV9=>N :>=F5=B@0FVW 70;V70 C 7@07:>2V V 28<V@NTBLAO D>B><5B@8G=> =0 570 =<. !:;04 @5035=BV2: R1 F5B0B=89 1CD5@ (pH 4,5) 122 <<>;L/; V4@>:A8;0<V=C 3V4@>E;>@84 220 <<>;L/; R2 V4@>:A8;0<V=C 3V4@>E;>@84 220 <<>;L/; $5@@>78= e" 3,0 <<>;L/; !B0=40@B 70;V70 500 <:3/4; (89,5 <:<>;L/;) >5DVFVT=B ?5@5@0EC=:C <:3/4; E 0,179 = <:<>;L/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 8,66 <:3/4; (1,55 <:<>;L/;) V=V9=VABL: 890 <:3/4; (160 <:<>;L/;) V0?07>= 28<V@N20==O: 8,66 890<:3/4; (1,55 160 <:<>;L/;) #<>28 715@V30==O 2V4 +2 4> +8 C. !10 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 01V@ @5035=BV2 ?@87=0G5=89 4;O :V;L:VA=>3> invitro 287=0G5==O A5G>2>W:8A;>B8 C A8@>20BFV V ?;07<V :@>2V, 0 B0:>6 2 A5GV ;N48=8. 3?0: $0AC20==O:=5 <5=H5R1: 5 x 44 <;, R2: 5 x 11 <;. !5G>20 :8A;>B0 T :V=F528< ?@>4C:B>< <5B01>;V7<C ?C@8=V2, =C:;5W=>28E:8A;>B V =C:;5>?@>B5W4V2. B65, 70=865==O 01> 7028I5==O @V2=O A5G>2>W:8A;>B8 A2V4G0BL ?@> ?>@CH5==O <5B01>;V7<C. !:;04 @5035=BV2: R1 Pipes-1CD5@ pH 7,0 50 <<>;L/; 4-0<V=>0=B8?V@8= (4AAP) 0,375 <<>;L/; #@8:070 e" 200 U/; R2 Pipes-1CD5@ pH 7,0 50 <<>;L/; %$! 1,92 <<>;L/; 5@>:A84070 e" 5000 U/; >5DVFVT=B ?5@5@0EC=:C <3/4; x 60 = <:<>;L/; >1>GV E0@0:B5@8AB8:8 =5 3V@H5 70: 'CB;82VABL: 0,28 <3/4; V=V9=VABL: 25 <3/4; V0?07>= 28<V@N20==O: 0,28 25 <3/4; #<>28 715@V30==O 2V4 +2 4> +8 C. !11 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L-:VABL V4?>2V4=VABL: B0:/=V 01V@ @5035=BV2 ?@87=0G5=89 4;O :V;L:VA=>3> invitro 287=0G5==O ;C6=>WD>AD0B078 ($) C A8@>20BFV V ?;07<V :@>2V ;N48=8. 8?0: $0AC20==O: R1: =5 <5=H5 2 E 44 <;, R2:=5 <5=H5 2 x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in vitro 287=0G5==O 7030;L=>3> 1V;V@C1V=C C A8@>20BFV V ?;07<V :@>2V ;N48=8. 2?0: $0AC20==O: 5035=B 1 =5 <5=H5 6E44 <;., 5035=B 2 =5 <5=H56E11 <;. 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"0:>6 4> A:;04C 2E>4OBL 10:B5@V>AB0B8G=V 035=B8. >=B@>;L=89 <0B5@V0;=040TBLAO C ;V>DV;V7>20=V9 D>@<V 704;O ?V428I5==O AB01V;L=>ABV 2<VABC. #<>28 715@V30==O 2V4 +2 4> +8 CC 70B5<=5=><C <VAFV. !15 09<5=C20==O ?@54<5B0 B0 9>3> ?0@0<5B@8 V;L:VABL V4?>2V4=VABL: B0:/=V 0;V1@0B>@ 283>B>2;5=89 =0 >A=>2V A8@>20B:8 :@>2V ;N48=8 V ?@87=0G5=89 4;O :0;V1@C20==O 1V>EV<VG=8E B5ABV2 =0 02B><0B8G=8E 0=0;V70B>@0E. 1?0: $0AC20==O:=5 <5=H5R1: 4 x 3 <;. 0;V1@C20;L=V 7=0G5==O =02>4OBLAO C A5@B8DV:0BV,2:070=89 C =L><C =><5@ ?0@BVW, <0T A?V2?040B8 V7 2:070=8<=0 D;0:>=V 7 ;V>DV;V7>20=8<:0;V1@0B>@><. =0G5==O:0;V1@0B>@0 287=0G0;8AO V7 70AB>AC20==O< <5B>4V2, 2:070=8EC A5@B8DV:0BV, >B@8<C20;8AO 2 AB0=40@B=8E C<>20E V @>7@0E>2C20;8AO70 @57C;LB0B0<8 0=0;V7C ?0@BVW :0;V1@0B>@0 2 45:V;L:>E =570;56=8E;01>@0B>@VOE. V>;>3VG=89 <0B5@V0;, 7 O:8E 283>B>2;5=89 :0;V1@0B>@, 1C2 ?5@52V@5=89 =0 2V4ACB=VABL 0=B8BV; 4> 2V@CAC V<C=>45DVF8BC ;N48=8 (), 4> 2V@CAC 35?0B8BC ! (HCV) V 4> ?>25@E=52>3> 0=B835=C2V@CAC 35?0B8BC  (HbsAg). 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