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5 $#?KBBM=IF JDAB HA=H =HJAHOM=I?=JA@! #? => LAJDA= JA?K>EJ= B II= E A>H=?DE= =HJAHO@E= AJAHM=I A=IKHA@ B =JA@=> LA JDAIOIJ KA )BJAH! E KJAIB MM=IHAIJ HA@>OHA HA =N=JE B>H=?DE= =HJAHOE HAIF IAJ B MM=I@AJAH E A@=BJAH E KJAI JHA =N=JE IMAHA@AJAH E A@=IL=I HA =N=JE E CK= EJH C O?AHE A=@ E EIJH=JE.,L= KAIMAHAANFHAIIA@=I B?D= CAE HA =JE J E AJAH 5J=JEIJE?= = = OIEI 4AIK JI=HAANFHAIIA@=I A= I± 5- H A@E= I±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

6 $$ A. B. C. Platelet superoxide production RLU/sec/ 10 5 platelets Thrombin induced platelet aggregation (RU) Collagen induced platelet aggregation (RU) Controls Controls Controls Risk factors Risk factors Risk factors.eckha 2 =JA AJIKFAH NE@A F= A =CCHAC=JE >E 7 F= A H? =CA C F= A +E F=JEA JIMEJD KJ?=H@E L=I?K =HHEI B=?J HI 5KFAH M=I A=IKHA@E M=IDA@F =JA AJIKIE C K?ECA E A D=?A@?DA E K E AI?A?A # # 2 =JA AJ=CCHAC=JE M=I@AJAH E A@ =I@AI?HE>A@E NAIE #JD FAH?A JE A E AIMEJDE > NAI A@E= I E AIMEJDE > A@E= AHI `H= CA B KJ OE CL= KAI F LI? JH F=H= AJAHIE =IK>CH KF BF=JEA JI IEC EBE?= JHA =JE IDEFM=IB >AJMAA F =JA AJIKFAH E HAIF IAJ? =CA 4 F 5.ECKHA ) 1 JAHAIJE C O IEC EBE?= JHA =JE IDEF M=I >IAHLA@MDA EJM=I=IIAIIA@E IK>CH C JDAFHAIA?A B HEI B=?J HIB H=JDAH I? AH IEIAEJDAH 5E E =H O IEC EBE?= JHA =JE IDEFM=I B HA =JE J JDH >E =JA JID M 4A =JE IDEF>AJMAA JDA =JA AJIKFAH NE@A JDA E= BK?JE? JDAHE F HJ= J@AJAH E = J BF =JA AJ BK?JE F=HJE?K =H OE F=JEA JIMEJD? E E?= HEI B=?J HIB H=JDAH I? AH IEI )?? H@E C O MAD=LA@AJAH E A@=HA =JE IDEF>AJMAA B M A@E=JA@@E =J=JE

7 $% B>H=?DE= =CA =JA AJ=CCHAC=JE 1 JDAIJK@EA@CH KF BIK> A?JI IEC EBE?= J=II?E=JE M=IB JDAIAF=H= AJAHI.ECKHA ) JE NE@= JABBA?JI B)H E= A =?=HF=ANJH=?JIE F =JA AJI`HA =JE IDEFJ?=H@E L=I?K =HHEI B=?J HFH BE A ANJMAE LAIJEC=JA@= JE NE@= JFH FAHJEAI BJDAANJH=?JI B) A =?=HF= =JKH= O??KHHE CF = J >AHHEAI BMDE?D=HAF=HJE?K =H OHE?DE = JE NE@=JELA F OFDA I=I@EI?KIIA@E JDA A 9A >IAHLA@JD=J F OFDA HE?DANJH=?JI B) A =?=HF= A=@J =IEC EBE?= J@A?HA=IAE IKFAH BH M=IDA@F =JA AJI OE IK> A?JIMEJD?=H@E L=I?K =HHEI B=?J HI E MD IKFAH M=I E EJE= OE?HA=IA@.ECKHA! >KJ JE F =JA AJIEI =JA@BH? JH CH KF IK> A?JIMEJD KJ?=H@E L=I?K =HHEI B=?J HI.ECKHA!) HA LAHIKFAH NE@A E F =JA AJIBH F=JEA JIMEJDDECD?=H@E L=I?K =HHEI M=I@A?HA=IA@ >O) A =?=HF=ANJH=?JIJ = ALA? F=H=> AJ ALA I >IAHLA@E =? JH CH 1JEI= I E F HJ= JJ JAJD=J O) A =?=HF= ) 240 Collagen induced platelet aggregation (RU) Platelet superoxide production RLU/sec/ 10 5 platelets Flow mediated dilatation (FMD % baseline) Collagen induced platelet aggregation (RU).ECKHA 4A =JE IDEFI>AJMAA F =JA AJ=CCHAC=JE E HAIF IAJ? =CA =JA AJIKFAH NE@A 2= A ) 4 F F =JA AJ JDA E= BK?JE 2= A 4! F 5

8 $& ) Platelet superoxide production RLU/sec/ 10 5 platelets Platelet superoxide production RLU/sec/ 10 5 platelets native A. Melanocarpa extract poliphenol concentration (µg/ml) (ug/ml) 0 native A. Melanocarpa extract poliphenol concentration (ug/ml) (µg/ml).eckha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

9 $' Controls Risk Factors Thrombin A. Melanocarpa extract polyphenol concentration(ug/ml) native Thrombin (20mU/ml) induced platelet aggregation (Relative Units) A. Melanocarpa extract polyphenol concentration(ug/ml) native Thrombin (20mU/ml) induced platelet aggregation (Relative Units) Collagen A. Melanocarpa extract polyphenol concentration(ug/ml) native Collagen (2ug/ml) (2µg/ml) induced platelet aggregation (Relative Units) A. Melanocarpa extract polyphenol concentration(ug/ml) native Collagen (2ug/ml) (2µg/ml) induced platelet aggregation (Relative Units).ECKHA" -BBA?JI BE?HA=IE C??A JH=JE I BF OFDA IBH ) A =?=HF=>AHHOANJH=?JI F =JA AJ=CCHAC=JE >E 7 J FF= A =CA KC > JJ F= A IBH? JH IK> A?JIHECDJF= A JIMEJDHEI B=?J HIB H=JDAH I? AH IEI ABJ F= A #JDFAH?A JE A E AIMEJDE > A@E= AHI `H= CA B KJ OE CL= KAI F LI? JH 2 JA JE= H A BF =JA AJ@AHELA@ E = JE =CCHAC=J HOABBA?JI B) A =?=HF=ANJH=?JI )IJDA= JE =CCHAC=J HOABBA?JI B) A J O BEJ\IABBA?JI IKFAH MA ANJE LAIJEC=JA@= F IIE>E EJOJD=J = H= JE =CCHAC=J HOABBA?J BHA =JELA ODECD??A JH=JE I B ) A =?=HF=ANJH=?JI=HA A@E=JA@>OEJ\IABBA?JI AJ=> EI D=I >AA ID M J >AHA A=IA@BH F =JA 5EI A BJDAE F HJ= JJ=HCAJI BF OFDA E?? F I )?? H@E C OF =JA AJ=CCHAC=JE M=IIJK@EA@E M=IDA@F =JA AJIEI =JA@ BH IK> A?JIMEJD L=I?K =HHEI FH BE AE E JDA=>IA?A B 5E DE>EJ H ) - 9A >IAHLA@JD=JFHA E?K>=JE BF =JA AJIMEJD ) -@E@ J?D= CAF =JA AJ=CCHAC=JE =J >=IA E >E H? =CA.ECKHA# HA LAH MA >IAHLA@JD=J ) -@E@ JE =CCHAC=J HOFH FAHJEAI B) A =?=HF= ANJH=?JI CJD=J 5@AHELA@ BH F =JA AJIEI J E L LA@E FH JE =CCHAC=J HOABBA?JI B) A =?=HF= F =JA AJI.ECKHA#

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11 $ )>E EJO BF =JA AJIJ E HA D MALAH IJIJK@EAIKIA@IJE K EMDE?DD=LA>AA ID M J IJE K =JA NE@=JELA >KHIJE AKJH FDE IA C 2 )$ =I= IKFAH E F =JA AJIM=I JIJK@EA@J IK?D= ANJA JI B=H =E O>A?=KIAIJK@EAIKIA@ BJA DA= JDO IK> A?JI MD = I E =FHAIA JIJK@O@A IJH=JALAHO M ALA I B>=I= IKFAH 9AID MDAHAJD=J= HA=@O=J>=IA E I F =JA AJI BH?=H@E L=I?K =HHEI F=JEA JE AI HAIKFAH NE@AJD=? JH I 1JEI= I JAM HJDOJD=JMAKIA@ M #??A JH=JE B K?ECA E E E EIDHEI B K?ECA E HA@ N?O? E CMDE?DD=I>AA =FH > A MEJD DECDAH K?ECA E??A JH=JE I 1JEI= I E F HJ= JJD=JMAFAHB H A@ =II=OI=J!% + MDE?DCHA=J OE?HA=IAIIA IEJELEJO BIKFAH NE@A=II=OIE ELE C?A I 6DAE?HA=IAE >=IA E JDAFHAIA J F=FAH =OD=LAIALAH= E F HJ= JBK?JE =? IAGKA?AI 5KFAH NE@A@EI KJ=IA5, =IMA =I ),20 NE@=IAE DE>EJ HI,21 =F?O E E DE>EJF =JA AJHA?HKEJ A JJ =FHAB H A@JDH >KIB ME C? =CA IJE K =JE " ),2E IKFAH =J= JI B? =CA =?JEL=JA@F =JA JDAFHAIA?A B5, HAIK JE CE MAH),2??A JH=JE I =L=E => AB HHA?HKEJ A J BBKHJDAHF =JA AJI" 1 JAHAIJE C OMDE A=L=IJ K >AH BF=FAHID=LA A@=JJDAABBA?JI J=IFA?JI BF =JA AJ =?JEL=JE I E@@=J=EI=L=E => A JDAABBA?JI5,M =C EIJ =JA AJ=CCHAC=JE H J =JA NE@AM B KA?A=C =JA AJ=CCHAC=JE MEJD KJ FHA B H A@JDH >KI" 5KFAH NE@AHA A=IA>O> JDF JDA E=?A EI= AOB=?J HE HACK =JE CF =JA AJ JDA E=?A E JAH=?JE =FHE =HOALA JE F =JA AJ =CCHAC=JE #.E = O F =JA AJ ),20 JIKFAH EI E F HJ= JE HACK =JE CF =JA AJ+," =IF=JEA JIMEJD CF'FD N@ABE?EA?OID MA@CHA=J O=> >OIALAH= IJE K E$ JA JE= E F HJ=?A BF =JA AJ ),20 NE@=IA E JDA? E E?= IAJJE C + B E?JE CHAIK JID=LA>AA >J=E A@MDA JDAABBA?JI BAN CA KI ELAHA@4 5 E LEJH F =JA AJ=CCHAC=JE MAHAIJK@EA@ 1 I AIJK@EAI N= JDE A N= JDE A NE@=IAIOIJA?=KIA@@A?HA=IA H=JDAHJD= = E?HA=IA B =CCHAC=JE % 6DAHA =JE IDEF>AJMAA F =JA AJIKFAH L=I?K =H HEI B=?J HIB =CHAA A JMEJDFHALE KIIJK@EAIJD=JID MJD=J =C EIJIJE K =JA@F =JA AJIKFAH EIDECDAHE F=JEA JIMEJD?=H@E L=I?K =HHEI B=?J HI E ADOFAHJA IE & H@E=>AJAI$ 5E E =H O F =JA AJIKFAH EIE?HA=IA@E JDAH@EIA=IAIKIK= O=II?E=JA@ MEJDE?HA=IA@L=I?K =H NE@=JELAIJHAII E A EJH=JAJ AH=?A & ) CE JA IE 11

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