& ) # ' $ $ ( % ! ! " % ! " " # $ # # "# # # " ' " #( " #& ) *+,- ./0 34 +1 2++ ! 355 % "6 73 +%%89%% : # 9 ( ; 7 !"# $!% ! • • • • •, • •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aboratorio Sustancias Leishmania Chagas Epi Chagas Tripo Malaria vitro Malaria vivo Antofagasta 36 1 6 0 3 2 Bogotá 83 28 4 2 8 0 Guatemala 52 21 5 3 0 0 México 81 12 7 11 0 Panamá 17 13 0 2 1 0 Salamanca 118 34 34 28 18 3 Tenerife 28 0 0 0 16 0 415 109 56 35 57 5 Total # # # # 3E 7 ? 3 ( D 3 ? D 6 @ < ; E 3 75 6 3 7 6 3 " , %!6 % 7 (-& " 1 - # ( 2:%2; # 5 =3 > , / . %( @ % ' A 2;%< 2<%28 28%72 71 1= 37 7= <= 7; :: 17 <3 ? 73 73 ++% S% ; 1; +S= CC 7:1 <= 37 7= 1: 728 ; 1; =0/ ' #( ) ) ,- ./1 +1 2++ ! µ U 1/T+//µ ,- .SS +C 2+1 .! ,- +%% += 2+S ! µ U 1/V.1µ ) ) ,- .81 +0 2+8 µ U 1/V.1µ &6 G7 ? ' EA 6 JE7 ! 3? .//+ 6 D H 3 !"# $!% 9 ; 7 N '* 788C'DE '* #7=F7;B 7 9 F76 6D H ? 5 @ 6D H ? D 676 , & B B # 3 7 ?6 ? J7 ? 3 6 7 6GB 35 76 3 @5 3 3 B E 7; " , %! ? 7 , ' A ; 7 7 % > .W 9 = 8 >0 9 C 8W > S 9 =W = S 8 % =W .W 8W C S =W 0 8 % = 1 +W . +/ #7? F77 B C'ED G 12? #7: F73 B H C'ED G 13? 8 8 % % C 8W =W +W 8 = % .W 1W 67 ; 63 ? ? ? ? 3 7 E 3! 5 6( > N 6B N 35 X C'(D7EG 12: 0 +1 2++ 4 5 3 @ ? 5 6 @ C'(D7EG 13: 0 +0 2+8 4 1%(6 E @ + 2 76 ? 52 8 / F76 7 52 S / % -;?2# 5 3 @ ? "6 5 7 6.9B .C .Y ! ? 35EJ3 ? 9QE 5 6( 9 C'(D7EG 13: 0 += 2+S 4 +0 2+8 4 +C 2+1 .4 +1 2++ 4 C'(D7EG 12: 0 C'(D7EG 1;< 0 C'(D7EG 122 0 +1 2+% 4 C'(D7EG 132 0 2+8 4 +. C'(D7EG 7;1 0 C'(D7EG 32< 0 +% 2+S 84 " : # # :<%;1I +1 2++ 4 C'(D7EG 122 0 += <:%87I C'(D7EG 12: 0 2+S 4 +0 2+8 4 8?%88I C'(D7EG 132 0 +1 2+% 4 4 2+8 +. C'(D7EG 7;1 0 C'(D7EG 13: 0 C'(D7EG 1;< 0 +C 2+1 .4 C'(D7EG 32< 0 +% 2+S 84 Biological Activity Aspects Leishmania amazonensis PH8 Immunological Aspects Wenner Gren Institute of Immunology Stockholm University Our results showed that the alkaloid extract of Evanta was not directly stimulating B cells, T cells or J774 macrophages, but it interfered with the activation of both mouse and human T cells, as seen by the reduction of cellular proliferation and in vitro induced production of IFN-γγ. It was established, as well, that the effect of CAT on the parasite was intense at 10 ug/ml and that it was stronger than the effect of the purified alkaloid, 2-phenylquinoline. 80 IC50 ug/mL 70 60 48.6 50 40 31.3 30 20 10 0 2FQ S.Y CAT +//Y CAT-2FQ Leishmania brasiliensis M2903 200 193.7 180 160 IC50 ug/mL Our results suggest that Evanta can control the chronic inflammatory reaction and therefore may contribute to the reduction of the pathology in the lesion. 83.1 90 140 120 100 80 51.3 60 32.3 40 20 0 2FQ CAT CAT-2FQ .CY $ .//. > .//%! 2 # $< +8Z10 1CSW [ 0CZ// 8/CW .%8 3 2 < # " ?6 # # < 4EQE +1Z.+ 8/.W [ 0SZ./ .8CW 1+= 3 7 2E # 3E 7 ? 3 ? 6D H D 6 @ 9 6B 8< :I 8: 2I 8: 8I 8: 1I 8 +" ' 3 #( 9+ 376A O * .//.9.//S 377E7 ? ; 37 3 G6 QEA 3> • ; 63 ? ? " E D 7 6N E 7 ? ? 6 9 ? ? # +=1 9 # N E E3 N 6 9 76 ? ; 37 3 7B 3 ? :E 7 9 9 • ) ) ,- ./1 +1 2++ ! µ U 1/T+//µ ,- .SS +C 2+1 .! ,- +%% += 2+S ! µ U 1/V.1µ ) ) ,- .81 +0 2+8 µ U 1/V.1µ : A L " # K # • • • • K 1/ T +/ U\ +/ U\ +/ U\ T +/ U\ O A 1< ! A 82 ! ìndice de Lesões (ULI) ULI (ìndice de Lesões Ulcerativas) 30 25 20 Controle 50 mg/kg 15 125 mg/kg 250 mg/kg Omeprazol 30 mg/kg 10 5 0 Contorções abdominais induzidas pelo ácido acético, i.p. 45 40 50 DI50 = 20,34 (15,81 - 26,17) mg/kg 45 35 30 40 n. co ntorções 37E? 3 5 76 3 (6E5 ; > 7H "6 B ? 6 4 35 44,0% ** 30 25 25 56,6% ** 20 64.4% ** 20 62,1% ** 15 10 15 10 5 5 0 controle 0 Controle 10 mg/kg 30 mg/kg 50 mg/kg 50 m/kg Galipea, via oral % & " !( " )!( ,(0 37 7 3 0 & 3!" "( ( E63 ? "6 "6 7< 6 76 @ QEA ND ? 37 7 3? 76 7 7 ? E63 @ B6 !"# $!% 3 34 73 2 9 .//S @ ? ; 7 !5 6 33 3 Numero de casos de leishmaniasis reportados en 2006 ! " ! $ $ % & ' ) ## (# ! * $ # $+ " , + +" & ' - . ' , . % / 0 & + , +, 2 ' % 1++0 & !. # & ' # & ' *# +" 3 +, ) ' " & ' , & ' $ )3 + --# ** & , # & ' ( -( #( !! ( (* #* ( # # # #( # Programa Nacional de Leishmaniasis " "#$ %$&'$ ?2%;?I C'(D7EG 12: 0 +1 12%=?I 2++ 4 #?2 J?2 K ) += C'(D7EG 122 0 2+S 4 #?2 12 J ?2 K ) ( C'(D7EG 13: 0 +0 2+8 4 C'(D7EG 1;< 0 +C 2+1 .4 +. 2+8 4 “Estudios químicos, biológicos y farmacológicos de Galipea longiflora, Krause”. A. Giménez, G. Ruiz, J.A. Avila, et al. Revista Boliviana de Química. Vol 22 No 1, 94-107, (2005). C'(D7EG 7;1 0 #?2 12 J ?2 K ) 7%=I C'(D7EG 32< 0 +% 2+S 84 Programa UMSA-ASDI-SAREC- Período 2004 – 2010 Proyecto: Enfermedades Infecciosas ”Estudios Clínicos Fase II de la Evanta en el Tratamiento de Leishmaniasis cutanea” •Universidad Mayor de San Andrés - UMSA •Facultad de Ciencias Farmacéuticas y Bioquímicas •CIDME-SELADIS –IIFB •Universidad de Estocolmo •Departamento de Inmunología •Hospital de Palos Blancos •Centro de Estudios •Proyecto OSCAR •Seguimiento de pacientes •Consejo Indigena de los Pueblos Tacana – CIPTA •Comunidad de Santa Rosa de Maravilla # < •, ! > ;2I / •( / / $ - / 6 ! / = 9 . + " + N # * # ( 9( "6 ? D6 ? 5 ? (-& 5 ? (-& 6B6 " & 3!" "( ( 6B6 " 4% 3 "( ( 3 5 3 R 6 + + = #D 6 79 @? + 2 2 E 6 U #US0U 9/+. U #US1U .%/8 . 2 35 7 ? #D 6 7 8 8 + 3 39 " + 9//. 6 E7G 6 6 6 2 35 7 " 3 3 6 Actividad antiparasitaria de Alcaloides Totales de Corteza de Galipea longiflora sobre 5 cepas nativas y 2 cepas de referencia 40 CI50ug/m L(CAT) " 5 ? 3@ 35 LB2 30 LC3 25 LB3 LD1 20 M2903 15 Lma 10 LBTE-002 5 0 1 Diferentes cepas de Leishmania (promastigotes) : ; < % ) %3 ) ." 9+ & ) 4 ! .# ) 1 $ %& )! .# ) ' !( ) ! ' ( ! (' !"# $!% = , " > % % & " !' ( (-& " ( (* 5 B @ 5 6" # 76 B 6 3 3 ? 3 7 E 6S # 4% 3 "( ( "6 " 7< ( % ( ) ." ' " ()+ ( +% /!( ( " #& # @ 7 ? "6 7 6 3U2 73 38 3 E "6 3 ? # # " # "# # " # A7E ? "6 ,A "# : N( .//% "# ( # 7 <L 6 M ! / ) ( > $ 6 Título abreviado del proyecto: Extractos Acuosos de Evanta Unidad Proponente: Instituto de Investigaciones Fármaco Bioquímicas: Unidad de Química Farmacéutica I B ? "6 3E 4 6 3 D 676 7* E 7 ? ? <# 4 6 3 $ 4 ? < 0" " . / 0, %& )+ %( 0" " <27K72K28 , &6 3 56 7 ! 5 3 7 1 3 = N N N N # # # <32K28K72 B ! $ ( $ ,A ! $F E6 6A ? "6 @ * 71 = 7< 3 3 • E7?? • 377E7 ? • D6 3 •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