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T*
[(possibility)-355(is)-355(an)-355(accumulation)-355(of)-355(a)-355(metabolite,)-355(such)-355(as)-355(the)]TJ
T*
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T*
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T*
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T*
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T*
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T*
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[(Chemicals)-234(were)-234(of)-234(analytic)-234(grade.)-234(Dry)-234(acetonitrile)-234(was)-234(obtained)]TJ
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[(commercially)-424(\(Pierce,)-424(Rockford,)-424(IL\).)]TJ
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(1)Tj
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[(H-nuclear)-424(magnetic)-424(reso-)]TJ
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[(nance)-592(\(NMR\))-592(spectra)-592(were)-592(recorded)-592(with)-592(a)-592(500-MHz)-592(Unity)]TJ
T*
[(spectrometer)-464(\(V)111(arian,)-464(Inc.,)-464(Palo)-409(Alto,)-464(CA\))-464(using)-464(CDCl)]TJ
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[(Si,)-220(0.00)-220(ppm\).)-220(R)]TJ
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T*
[(Routine)-520(column)-520(chromatography)-520(was)-520(performed)-520(under)-520(normal)]TJ
T*
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T*
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[(Methyl)-249(15-Hydroxy-3-oxa-pentadecanoate)]TJ
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[(12-T)70(etrahydropyranyloxy-1-dodecanol)-620(was)-620(synthesized)-620(from)]TJ
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[(1,12-dodecanediol)-417(as)-417(previously)-417(described)-417(\()]TJ
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(13)Tj
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[(\).)-399(This)-417(alcohol)-417(\(5)]TJ
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(t)Tj
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[(-butyl)-353(bromoacetate)-353(\(20)-353(mmol\))]TJ
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[(and)-215(tetrabutylammonium)-215(hydrogen)-215(sulfate)-215(\(5)-215(mmol\))-215(in)-215(20)-215(mL)-178(50%)]TJ
T*
[(NaOH)-231(and)-231(15)-231(mL)-194(CH)]TJ
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(2)Tj
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(Cl)Tj
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(2)Tj
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[(at)-231(room)-231(temperature)-231(fo)]TJ
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[(r)-231(4)-231(h)-231(according)-231(to)]TJ
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[(a)-285(previously)-285(described)-285(procedure)-285(\()]TJ
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(14)Tj
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[(\).)-267(The)-285(solution)-285(was)-285(extracted)]TJ
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(4)Tj
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[(evaporated)-365(under)-365(reduced)-365(pressure.)-347(The)-365(product)-365(of)-365(this)-365(reaction,)]TJ
/F12 1 Tf
T*
(t)Tj
/F11 1 Tf
0.278 0 TD
[(-butyl)-532(15-tetrahydropyranyloxy-3-oxa-pentadecanoate,)-532(was)-532(iso-)]TJ
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[(lated)-387(by)-387(liquid)-387(chromatography)-387(\(hexane:ethyl)-387(acetate,)-387(3:1;)-387(R)]TJ
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(f)Tj
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(5)Tj
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[(0.7\).)-277(This)-295(product)-295(was)-295(directly)-295(caused)-295(to)-295(react)-295(in)-295(methanol)-295(with)-295(a)]TJ
T*
[(catalytic)-326(amount)-326(of)-326(p-toluenesulfonic)-326(acid)-326(fo)]TJ
18.3481 0 TD
0.326 Tc
[(r6ha)326(t)]TJ
3.3591 0 TD
0 Tc
[(re\257ux.)-271(After)]TJ
-21.7073 -1.2222 TD
[(neutralization)-268(of)-268(the)-268(solution)-268(with)-268(sodium)-268(bicarbonate,)-268(the)-268(solvent)]TJ
T*
[(was)-244(evaporated.)-244(Ether)-244(\(20)-244(mL\))-244(and)-244(brine)-244(\(20)-244(mL\))-244(were)-244(added,)-244(and)]TJ
T*
[(the)-213(or)18(ganic)-213(layer)-213(was)-213(dried)-213(\(MgSO)]TJ
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(4)Tj
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[(\))-213(and)-213(evaporated)-213(under)-213(reduced)]TJ
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[(pressure.)-407(The)-425(product,)-425(methyl)-425(15-hydroxy-3-oxa-pentadecanoate)]TJ
T*
[(\(2.3)-620(mmol,)-620(46%\),)-620(was)-620(isolated)-620(as)-620(a)-620(colorless)-620(oil)-620(by)-620(liquid)]TJ
T*
[(chromatography)-410(\(hexane:ethyl)-410(acetate,)-410(7:3;)-410(R)]TJ
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(f)Tj
/F4 1 Tf
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(5)Tj
/F11 1 Tf
1.2433 0 TD
(0.3\).)Tj
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(1)Tj
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(H-NMR)Tj
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[(1.2\2611.65)-589(\(m,)-589(20H,)-589(CH)]TJ
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(2)Tj
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[(\),)-589(3.52)-589(\(t,)-589(2H,)-589(C\(4\)H)]TJ
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(2)Tj
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[(\),)-589(3.64)-589(\(t,)-589(2H,)]TJ
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(C\(15\)H)Tj
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(2)Tj
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[(\),)-233(3.76)-233(\(s,)-233(3H,)-233(-COOCH)]TJ
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(3)Tj
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[(\),)-233(4.08)-233(\(s,)-233(3H,)-233(C\(2\)H)]TJ
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(2)Tj
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(\).)Tj
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[(Methyl)-249(15-Iodo-3-oxa-pentadecanoate)]TJ
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1.1111 -1.3333 TD
[(T)70(o)-282(2.1)-282(mmol)-282(methyl)-282(15-hydroxy-3-oxa-pentadecanoate)-282(in)]TJ
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(N,N)Tj
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(-)Tj
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T*
[(phine,)-284(and)-284(the)-284(solution)-284(was)-284(stirred)-284(at)-284(room)-284(temperature)-284(for)-284(5)-284(min.)]TJ
T*
[(T)70(o)-419(this)-419(solution)-419(was)-419(added)-419(iodine)-419(crystals)-419(until)-419(a)-419(reddish)-419(color)]TJ
T*
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T*
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T*
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(4)Tj
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T*
[(pentadecanoate,)-415(was)-415(isolated)-415(as)-415(an)-415(oil)-415(in)-415(90%)-415(yield)-415(by)-415(column)]TJ
T*
[(chromotography)-480(\(hexane:ethyl)-480(acetate,)-480(3:1\).)-480(TLC)-480(\(hexane:ethyl)]TJ
T*
[(acetate,)-306(3:1;)-306(R)]TJ
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(f)Tj
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(5)Tj
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(1)Tj
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[(H-NMR)-306(1.2\2611.65)-306(\(m,)-306(20H,)-306(CH)]TJ
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(2)Tj
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[(\),)-306(3.19)-306(\(t,)]TJ
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(2)Tj
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(2)Tj
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[(\).)-215(The)-233(compound)-233(was)-233(stable)-233(when)-233(kept)-233(at)-233(5\311C.)]TJ
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([)Tj
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(19)Tj
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[(F]Fluoro-3-oxa-pentadecanoic)-212(Acid)]TJ
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[(in)-402(tetrahydrofuran)-402(was)-402(added)-402(1.15)-402(mmol)-402(methyl)-402(15-iodo-3-oxa-)]TJ
T*
[(pentadecanoate.)-217(The)-235(solution)-235(was)-235(stirred)-235(at)-235(room)-235(temperature)-235(for)-235(4)]TJ
T*
[(h.)-313(Ether)-313(\(20)-313(mL\))-313(and)-313(water)-313(\(20)-313(mL\))-313(were)-313(added,)-313(and)-313(the)-313(or)18(ganic)]TJ
T*
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(4)Tj
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[(\))-283(and)-283(evaporated)-283(under)-283(reduced)-283(pressure.)]TJ
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[(The)-311(resultant)-311(\257uoroester)-311(was)-311(isolated)-311(by)-311(column)-311(chromatography)]TJ
T*
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[(\(hexane:ethyl)-199(acetate,)-199(3:1\).)-181(TLC)-199(\(hexane:ethyl)-199(acetate,)-199(3:1\))-199(showed)]TJ
T*
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(f)Tj
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[(ethanol)-236(and)-236(0.2-N)-236(KOH)-236(\(1:1\))-236(at)-236(room)-236(temperature)-236(overnight.)-181(After)]TJ
T*
[(evaporation)-317(of)-317(most)-317(of)-317(the)-317(ethanol,)-317(ether)-317(\(30)-317(mL\))-317(and)-317(dilute)-317(HCl)]TJ
T*
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T*
(\(MgSO)Tj
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(4)Tj
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[(\),)-437(and)-437(evaporated)-437(under)-437(reduced)-437(pressure.)-419(The)-437(product,)]TJ
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(15-[)Tj
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(19)Tj
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[(F]\257uoro-3-oxa-pentadecanoic)-342(acid,)-342(was)-342(crystallized)-342(in)-341(60%)]TJ
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[(yield)-271(from)-271(hexane)-271(\(melting)-271(point)]TJ
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(5)Tj
/F11 1 Tf
1.1041 0 TD
(38\311C\).)Tj
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(1)Tj
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[(H-NMR)-271(1.2\2611.65)-271(\(m,)]TJ
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[(20H,)-216(CH)]TJ
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(2)Tj
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[(\),)-216(3.52)-216(\(t,)-216(2H,)-216(C\(4\)H)]TJ
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(2)Tj
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[(\),)-216(4.08)-216(\(s,)-216(3H,)-216(C\(2\)H)]TJ
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(2)Tj
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[(\),)-216(4.44)-216(\(dt,)-216(2H,)]TJ
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(C\(15\)H)Tj
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(2)Tj
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0.233 Tc
(,J)Tj
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0 Tc
(HF)Tj
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(5)Tj
/F11 1 Tf
1.0656 0 TD
[(47.5)-233(Hz,)-233(J)]TJ
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(HH)Tj
/F4 1 Tf
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(5)Tj
/F11 1 Tf
1.0656 0 TD
[(6.2)-233(Hz\).)]TJ
/F14 1 Tf
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(18)Tj
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[(F-Labeling)-249(Procedure)]TJ
/F11 1 Tf
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[(The)-373(radio\257uorination)-373(procedure)-373(was)-373(that)-373(of)-373(DeGrado)-373(\()]TJ
/F12 1 Tf
22.7713 0 TD
(15)Tj
/F11 1 Tf
0.9999 0 TD
[(\),)-373(as)]TJ
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[(modi\256ed)-569(from)-569(that)-569(of)-569(Coenen)-569(et)-569(al.)-569(\()]TJ
/F12 1 Tf
16.9002 0 TD
(16)Tj
/F11 1 Tf
0.9999 0 TD
[(\).)-551(The)-569(precursor)-569(for)]TJ
5.987 0 0 5.987 311.488 358.877 Tm
(18)Tj
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[(F-labeled)-360(FOP)-324(was)-360(methyl)-360(15-iodo-3-oxa-pentadecanoate.)-342(T)70(o)-360(a)]TJ
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[(2-mL)-520(glass)-557(vial)-557(was)-557(added)-557(Krypto\256x)-557(2.2.2)-557(\(10)-557(mg;)-502(Aldrich,)]TJ
T*
[(Milwaukee,)-185(WI\),)-203(acetonitrile)-203(\(0.5)-203(mL\),)-203(and)-203(a)-203(9)0(%)-203(K)]TJ
5.987 0 0 5.987 492.957 332.685 Tm
(2)Tj
8.98 0 0 8.98 495.951 334.182 Tm
(CO)Tj
5.987 0 0 5.987 508.424 332.685 Tm
(3)Tj
8.98 0 0 8.98 513.237 334.182 Tm
[(solution)-203(in)]TJ
-22.4661 -1.2222 TD
[(water)-406(\(20)-406(\177L\).)-406([)]TJ
5.987 0 0 5.987 372.547 325.95 Tm
(18)Tj
8.98 0 0 8.98 378.535 323.206 Tm
[(F]\257uoride,)-406(produced)-406(through)-406(proton)-406(bombard-)]TJ
-7.4661 -1.2222 TD
[(ment)-423(of)-423(H)]TJ
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(2)Tj
0.5001 0.7083 TD
(18)Tj
8.98 0 0 8.98 359.982 312.23 Tm
0.423 Tc
(O\()Tj
/F4 1 Tf
1.4776 0 TD
0 Tc
(.)Tj
/F11 1 Tf
0.8329 0 TD
[(95)-423(atom)-423(%\),)-423(was)-423(then)-423(added;)-423(the)-423(vessel)-423(was)]TJ
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[(placed)-267(in)-267(an)-267(aluminum)-267(heating)-267(block)-267(at)-267(85\311C;)-267(and)-267(the)-267(solvent)-267(was)]TJ
T*
[(evaporated)-289(under)-289(a)-289(stream)-289(of)-289(helium)-289(or)-289(nitrogen.)-271(The)-289(residue)-289(was)]TJ
T*
[(further)-362(dried)-362(by)-362(azeotropic)-362(distillation)-362(with)-362(acetonitrile)-362(\(2)]TJ
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T*
[(in)-385(acetonitrile)-385(\(0.5)-385(mL\))-385(was)-385(added,)-385(and)-385(the)-385(vial)-385(was)-385(sealed)-385(and)]TJ
T*
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T*
[(was)-293(brie\257y)-293(cooled)-293(by)-293(placing)-293(it)-293(in)-293(ice)-293(water)55(.)-275(The)-293(incorporation)-293(of)]TJ
T*
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T*
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T*
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T*
[(to)-327(a)-327(semipreparative)-327(reverse-phase)-327(high-performance)-327(liquid)-327(chro-)]TJ
T*
[(matography)-237(\(HPLC\))-237(column)-237(\(Nuclosil)-237(C-18)-237([10)-237(\177,)-237(250)]TJ
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(3)Tj
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T*
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T*
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/Im1 Do
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[(FIGURE)-233(1.)]TJ
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(18)Tj
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[(F-labeled)-233(fatty)-233(acids.)]TJ
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(1728)Tj
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(N)Tj
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(x)Tj
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(18)Tj
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[(dryness,)-338(formulated)-338(in)-338(isotonic)-338(NaCl)-338(solution)-338(with)-338(1%\2612%)-338(albu-)]TJ
T*
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T*
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[(Female)-371(Sprague-Dawley)-371(rats)-371(\(body)-371(weight)-371(range,)-371(180\261225)-371(g\))]TJ
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[(fasted)-243(overnight.)-225(The)-243(rats)-243(were)-243(anesthetized)-243(with)-243(pentobarbital)-243(\(75)]TJ
T*
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T*
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(18)Tj
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[(F-labeled)-313(FOP)-276(\(20\26140)-313(\177Ci\))-313(was)]TJ
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[(injected)-313(into)-313(the)-313(femoral)-313(vein.)-258(A)-258(prescribed)-313(duration)-313(was)-313(allowed)]TJ
T*
[(before)-434(procurement)-434(of)-434(tissues)-434(\(heart,)-434(liver)40(,)-434(lung,)-434(blood,)-434(kidney)65(,)]TJ
T*
[(bone)-404([rib],)-404(brain)-404([whole],)-404(skeletal)-404(muscle,)-404(and)-404(urinary)-404(bladder\).)]TJ
T*
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T*
[(corrected)-233(for)-233(decay)65(.)-233(Radiotracer)-233(uptake)-233(was)-233(calculated)-233(as:)]TJ
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-0.03 Tc
[(Uptake)-221(\(%)-221(dose)-221(kg/g\))]TJ
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(5)Tj
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-0.03 Tc
[(\(%)-221(injected)-221(dose\)\(rat)-221(weight)-221([kg]\))]TJ
ET
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0 J 0 j 0.499 w 10 M []0 d
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257.511 573.361 l
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BT
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[(tissue)-221(mass)-221(\(g\))]TJ
9.2671 0.7083 TD
0 Tc
[(.)-2096(Eq.)-250(1)]TJ
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[(In)-400(one)-400(group)-400(of)-400(fasting)-400(rats,)-400(the)-400(carnitine)-400(palmitoyltransferase)-400(I)]TJ
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[(\(CPT)92(-I\))-468(inhibitor)40(,)-468(etomoxir)-468(\(40)-468(mg/kg;)-468(Byk)-468(Gulden,)-468(Konstanz,)]TJ
T*
[(Germany\),)-527(was)-527(administered)-527(intraperitoneall)]TJ
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[(y)-527(2)-527(h)-527(before)-527(FOP)]TJ
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(injection.)Tj
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[(Analysis)-249(of)-249(Radiolabeled)-249(Metabolites)-249(in)-249(T)18(issues)]TJ
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[(The)-218(chemical)-218(nature)-218(of)-218(the)-218(metabolites)-218(in)-218(the)-218(liver)-218(and)-218(heart)-218(was)]TJ
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(17)Tj
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T*
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[(was)-604(thoroughly)-603(homogenized)-604(and)-603(sonicated)-603(\(20)-603(s\))-604(in)-603(7)-603(m)0(L)]TJ
T*
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T*
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T*
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T*
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T*
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-0.003 Tc
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0 Tc
[(lized)-362(FOP)111(.)-362(Samples)-362(of)-362(serum)-362(were)-362(obtained)-362(from)-362(blood)-362(samples)]TJ
T*
[(drawn)-267(from)-267(the)-267(left)-267(ventricle)-267(20)-267(min)-267(after)-267(injection)-267(of)-267(FOP)111(.)-249(T)70(o)-267(0.3)]TJ
T*
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T*
[(and)-438(centrifuged.)-420(The)-438(supernatant)-438(was)-438(\256ltered)-438(\(13-mm-diameter)40(,)]TJ
T*
[(0.2-\177m)-495(nylon)-495(\256lter\))-495(and)-495(analyzed)-495(for)-495(nonmetabolized)-495(FOP)-458(by)]TJ
T*
[(analytic)-223(reverse-phase)-223(HPLC)-223(\(Econosphere)-223(C-18)-223([5)-223(\177m,)-223(250)]TJ
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(3)Tj
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(4.6)Tj
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[(mm];)-336(Alltech\))-390(with)-390(the)-390(eluent)-390(MeOH:water:acetic)-390(acid,)-390(85:14.5:)]TJ
T*
[(0.5,)-357(at)-357(a)-357(\257ow)-357(of)-357(1)-357(mL/min.)-357(HPLC)-357(eluent)-357(samples)-357(were)-357(continu-)]TJ
T*
[(ously)-358(collected)-358(and)-358(counted)-358(in)-358(a)-358(well)-358(counter)55(.)-358(FOP)-321(eluted)-358(at)-358(5.8)]TJ
T*
[(min.)-284(The)-302(amount)-302(of)-302(radioactivity)-302(in)-302(the)-302(samples)-302(corresponding)-302(to)]TJ
T*
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T*
[(radioactivity)-451(injected.)-451(Control)-451(samples)-451(of)-451(nonradioactive)-451(serum)]TJ
T*
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T*
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[(fasted)-627(overnight.)-572(After)-627(anesthetization)-627(with)-627(pentobarbital)-627(\(75)]TJ
T*
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T*
[(cavity)-637(was)-637(opened)-637(and)-637(the)-637(portal)-637(vein)-637(was)-637(cannulated)-637(and)]TJ
T*
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22.7986 0 TD
(,)Tj
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[(wet)-504(weight\))-504(was)-504(then)-504(dissected)-504(free)-504(and)-504(placed)-504(on)-504(a)-504(1.5-cm-)]TJ
T*
[(diameter)-212(grate)-212(across)-212(the)-212(opening)-212(of)-212(a)-212(small)-212(funnel.)-194(The)-212(funnel)-212(was)]TJ
T*
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T*
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T*
[(composition)-352(\(in)-352(mmol/L\):)-352(Na)]TJ
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(1)Tj
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[(,)-352(143;)-352(K)]TJ
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(1)Tj
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[(,)-352(5.9;)-352(Ca)]TJ
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(2)Tj
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(1)Tj
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[(,)-352(1.85;)-352(Mg)]TJ
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(2)Tj
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(1)Tj
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[(1.0;)-247(Cl)]TJ
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(2)Tj
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[(,)-247(125.6;)-247(SO)]TJ
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(2)Tj
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(2)Tj
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(4)Tj
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[(,)-247(1.18;)-247(H)]TJ
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(2)Tj
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(PO)Tj
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(2)Tj
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(4)Tj
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[(,)-247(1.2;)-247(HCO)]TJ
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(2)Tj
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(3)Tj
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[(,)-247(25;)-247(glucose,)-247(5;)]TJ
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[(using)-358(5-\177m)-358(in-line)-358(\256lters)-358(\(Millipore\).)-358(Under)-358(standard)-358(conditions,)]TJ
T*
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(2)Tj
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[(:5%)-214(CO)]TJ
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(2)Tj
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[(.)-196(T)70(o)-214(assess)-214(the)-214(tracer)]TJ
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T*
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(2)Tj
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[(fraction)-394(at)-394(5%.)-376(The)]TJ
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[(makeup)-567(gas)-567(was)-567(nitrogen.)-549(The)-567(apparatus)-567(used)-567(water)20(-jacketed)]TJ
T*
[(vessels)-234(and)-234(a)-234(heater\261circulator)-234(to)-234(deliver)-234(the)-234(medium)-234(to)-234(the)-234(liver)-234(at)]TJ
T*
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T*
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T*
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T*
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(18)Tj
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[(F)-280(radioac-)]TJ
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[(tivity)-353(required)-353(close)-354(monitoring)-354(by)-353(external)-354(detectors.)-336(Therefore,)]TJ
T*
[(the)-593(temperature)-593(of)-593(the)-593(liver)-593(was)-593(not)-593(strictly)-593(controlled.)-575(The)]TJ
T*
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T*
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T*
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T*
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[(For)-443(pulse)-443(perfusion)-443(of)-443(radiotracers,)-443(2)-443(reservoirs)-443(of)-443(perfusate)]TJ
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6.486 0 0 6.486 109.407 480.841 Tm
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9.978 0 0 9.978 115.893 477.848 Tm
[(F]\257uoride\))-252(to)-252(be)-252(e)12(f)25(fectively)-252(reabsorbed)-252(by)-252(the)]TJ
-5.5973 -1.2 TD
[(kidneys.)-271(Using)-271(only)-271(the)-271(nonmetabolized)-271(FOP)-234(concentration)]TJ
T*
[(in)-333(blood,)-333(the)-333(liver)20(-to-blood)-333(ratio)-333(was)-333(decreased)-333(68%)-333(\()]TJ
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-23.1682 -1.2 TD
[(0.00005\))-283(with)-283(CPT)92(-I)-283(inhibition)-283(15)-283(min)-283(after)-283(injection,)-283(from)]TJ
T*
(30.5)Tj
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[(4.5)-255(for)-255(control)-255(rats)-255(to)-255(9.8)]TJ
/F4 1 Tf
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(6)Tj
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[(3.6)-255(for)-255(etomoxir)20(-treated)]TJ
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[(rats.)-227(Analysis)-282(of)-282(liver)-282(homogenates)-282(showed)-282(more)-282(than)-282(88%)]TJ
T*
[(of)-546(the)-546(radioactivity)-546(to)-546(be)-546(or)18(ganic)-546(soluble)-546(15)-546(min)-546(after)]TJ
T*
[(injection)-505(for)-505(both)-505(normal)-505(and)-505(CPT)92(-I)-505(inhibited)-505(rat)-505(livers)]TJ
T*
[(\(T)70(able)-233(2\).)]TJ
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[(FOP)-282(kinetics)-319(in)-319(isolated)-319(rat)-319(liver)-319(showed)-319(rapid)-319(and)-319(slow)]TJ
-1 -1.2 TD
[(turnover)-208(\(Fig.)-208(5\).)-190(The)-208(rapid)-208(process)-208(was)-208(most)-208(apparent)-208(in)-208(the)]TJ
T*
[(\256rst)-530(4)-530(min)-530(of)-530(washout;)-530(thereafter)40(,)-530(the)-530(slower)-530(clearance)]TJ
25.2 15.3031 TD
[(process)-278(was)-278(evident.)-260(The)-278(kinetics)-278(were)-278(successfully)-278(\256t)-278(by)-278(a)]TJ
0 -1.2 TD
[(2-compartment)-342(model)-342(\(Fig.)-342(6\),)-342(allowing)-342(estimation)-342(of)-342(rate)]TJ
T*
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9.978 0 0 9.978 358.981 456.925 Tm
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9.978 0 0 9.978 372.202 456.925 Tm
[(.)-195(T)70(able)-213(3)-213(shows)-213(the)-213(mean)-213(values)-213(of)-213(parameter)]TJ
-6.0848 -1.2 TD
[(estimates)-402(in)-402(normoxic)-402(and)-402(hypoxic)-402(groups.)-384(The)-402(only)-402(rate)]TJ
T*
[(constant)-323(in\257uenced)-323(signi\256cantly)-323(by)-323(hypoxia)-323(was)-323(k)]TJ
6.486 0 0 6.486 517.63 431.232 Tm
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[(,)-323(which)]TJ
-20.9848 -1.2 TD
[(was)-309(increased)-309(2.6-fold)-309(over)-309(normal)-309(values.)-291(The)-309(increase)-309(in)]TJ
T*
(k)Tj
6.486 0 0 6.486 316.477 407.285 Tm
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[(with)-342(hypoxia)-342(translated)-342(into)-342(decreases)-342(of)-342(both)-342(DV)]TJ
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6.486 0 0 6.486 325.895 395.311 Tm
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9.978 0 0 9.978 329.138 397.057 Tm
[(,)-295(because)-295(both)-295(DV)-277(estimates)-295(are)-295(inversely)-295(proportional)]TJ
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9.978 0 0 9.978 334.892 385.084 Tm
[(\(Eq.)-371(8\).)-353(The)-371(decreases)-371(in)-371(DV)]TJ
6.486 0 0 6.486 456.853 383.338 Tm
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9.978 0 0 9.978 460.096 385.084 Tm
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[(,D)371(V)]TJ
6.486 0 0 6.486 480.702 383.338 Tm
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(2)Tj
9.978 0 0 9.978 483.945 385.084 Tm
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6.486 0 0 6.486 522.664 383.338 Tm
(tot)Tj
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-22.222 -1.2 TD
[(hypoxia)-430(tracked)-430(closely)-430(the)-430(55%)-430(decrease)-430(in)-430(FPOR.)-412(The)]TJ
T*
[(strongest)-401(correlation)-401(with)-401(FPOR)-401(was)-401(found)-401(for)-401(k)]TJ
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ET
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7.2983 1.25 TD
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-0.7351 -1.25 TD
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8.2152 1.25 TD
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-1.652 -1.25 TD
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-25.9373 -1.25 TD
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[(\))-422(conditions.)-422(Livers)-422(were)-422(pulse)-422(perfused)-422(with)]TJ
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[(radiotracer)-652(in)-652(perfusate)-652(at)-652(constant)-652(concentration)-652(over)-652(the)]TJ
T*
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T*
[(acids)-278(had)-278(no)-278(e)12(f)25(fect)-278(on)-278(palmitoyl-carnitine)-278(oxidation)-278(in)-278(liver)]TJ
T*
[(mitochondria)-233(\()]TJ
/F12 1 Tf
5.8989 0 TD
(12)Tj
/F11 1 Tf
0.9999 0 TD
[(\).)-215(The)-233(mechanisms)-233(underlying)-233(these)-233(di)12(f)25(fer)20(-)]TJ
-6.8989 -1.2 TD
[(ences)-292(were)-292(not)-292(clari\256ed,)-292(but)-292(a)-292(metabolite)-292(of)-292(the)-292(3-oxa)-292(fatty)]TJ
T*
[(acid)-216(likely)-216(accumulated)-216(in)-216(the)-216(mitochondrion)-216(and)-216(caused)-216(the)]TJ
T*
[(inhibition)-476(of)]TJ
/F4 1 Tf
5.6739 0 TD
(b)Tj
/F11 1 Tf
0.611 0 TD
[(-oxidation)-476(at)-476(1)-476(o)0(r)-476(more)-476(steps)-476(beyond)-476(the)]TJ
-6.2848 -1.2 TD
-0.002 Tc
[(CPT)92(-I)-197(step)-197(\(carnitine)-197(acylcarnitine-translocase,)-197(CPT)92(-II,)-197(very-)]TJ
T*
0 Tc
[(long-chain)-314(dehydrogenase,)-314(mitochondrial)-314(trifunctional)-314(pro-)]TJ
T*
[(tein,)-374(etc.\).)-357(The)-374(accumulation)-374(of)-374(a)-374(radiolabeled)-374(3-oxa)-374(fatty)]TJ
T*
[(acid)-251(in)-251(liver)-251(was)-251(anticipated)-251(to)-251(potentially)-251(serve)-251(as)-251(a)-251(marker)]TJ
T*
[(of)-233(mitochondrial)-233(oxidative)-233(metabolism)-233(of)-233(fatty)-233(acids.)]TJ
1 -1.2 TD
[(FOP)-220(is)-257(taken)-257(up)-257(avidly)-257(by)-257(liver)-257(in)-257(the)-257(living)-257(rat.)-239(The)-257(high)]TJ
-1 -1.2 TD
[(ratio)-225(of)]TJ
6.486 0 0 6.486 91.128 336.056 Tm
(18)Tj
9.978 0 0 9.978 97.613 333.062 Tm
[(F)-225(radioactivity)-225(concentration)-225(in)-225(liver)-225(relative)-225(to)-225(the)]TJ
-3.7653 -1.2 TD
[(concentration)-573(of)-573(intact)-573(FOP)-536(in)-573(blood)-573(\(30.5:1\))-573(provides)]TJ
T*
[(evidence)-299(of)-299(a)-299(mechanism)-299(of)-299(binding)-299(or)-299(metabolic)-299(retention)]TJ
T*
[(of)-633(the)-633(tracer)-633(in)-633(tissue.)-633(Comparison)-633(of)-633(data)-633(from)-633(our)]TJ
T*
[(laboratory)-439(in)-439(the)-439(same)-439(isolated)-439(rat)-439(liver)-439(model)-439(using)-439(the)]TJ
T*
[(4-thia)-607(tracer)40(,)-607(FTP)-570(\()]TJ
/F12 1 Tf
8.6592 0 TD
(10)Tj
/F11 1 Tf
0.9999 0 TD
[(\),)-607(suggests)-607(a)-607(slower)-607(intracellular)]TJ
-9.6592 -1.2 TD
[(sequestration)-432(of)-432(FOP)-395(relative)-432(to)-432(FTP)111(,)-432(consistent)-432(with)-432(the)]TJ
T*
[(observed)-263(50%)-263(slower)-263(rate)-263(of)-263(activation)-263(of)-263(3-oxa-heptadeca-)]TJ
T*
[(noic)-362(acid)-362(relative)-362(to)-362(a)-362(4-thia-stearic)-362(acid)-362(by)-362(in)-362(vitro)-362(assay)]TJ
T*
(\()Tj
/F12 1 Tf
0.333 0 TD
(24)Tj
/F11 1 Tf
0.9999 0 TD
[(\).)-402(The)-420(much)-420(lower)-420(uptake)-420(of)-420(FOP)-383(in)-420(heart)-420(relative)-420(to)]TJ
-1.3329 -1.2 TD
[(myocardial)-371(uptake)-371(of)-371(palmitate)-371(\()]TJ
/F12 1 Tf
13.5364 0 TD
(25)Tj
/F11 1 Tf
0.9999 0 TD
[(\))-371(o)0(r)-371(4)0(-)-371(and)-371(6-thia)-371(fatty)]TJ
-14.5364 -1.2 TD
[(acid)-250(analogs)-250(\()]TJ
/F12 1 Tf
5.5537 0 TD
(9,10,17)Tj
/F11 1 Tf
2.9998 0 TD
[(\))-250(i)0(s)-250(intriguing.)-250(Di)12(f)25(ferences)-250(in)-250(activities)]TJ
-8.5536 -1.2 TD
[(of)-319(enzymes)-319(and)-319(carriers)-319(of)-319(fatty)-319(acid)-319(use)-319(in)-319(liver)-319(and)-319(heart)]TJ
T*
[(for)-452(the)-452(3-oxa)-452(fatty)-452(acid)-452(are)-452(implicated.)-434(T)70(w)0(o)-452(isoforms)-452(of)]TJ
T*
[(CPT)92(-I)-206(are)-206(known)-206(to)-206(exist;)-206(one)-206(is)-206(predominant)-206(in)-206(liver)-206(and)-206(the)]TJ
T*
[(other)-210(in)-210(heart)-210(\()]TJ
/F12 1 Tf
5.7954 0 TD
(26)Tj
/F11 1 Tf
0.9999 0 TD
[(\).)-192(The)-210(liver)-210(form)-210(of)-210(CPT)92(-I)-210(may)-210(have)-210(greater)]TJ
-6.7954 -1.2 TD
[(activity)-454(with)-454(3-oxa)-454(fatty)-454(acids)-454(than)-454(does)-454(the)-454(heart)-454(form.)]TJ
T*
[(Alternatively)65(,)-284(d)0(i)12(f)25(ferences)-284(in)-284(molecular)-284(speci\256cities)-284(of)-284(long-)]TJ
T*
[(chain)-445(acyl-CoA)-390(synthetase)-445(could)-445(be)-445(present)-445(in)-445(heart)-445(and)]TJ
T*
[(liver)40(,)-287(o)0(r)-287(acyl-CoA)-232(or)-287(acylcarnitine)-287(hydrolases)-287(may)-287(be)-287(more)]TJ
T*
[(prevalent)-410(in)-410(heart)-410(and)-410(therefore)-410(result)-410(in)-410(more)-410(prominent)]TJ
T*
[(clearance)-233(of)-233(3-oxa)-233(fatty)-233(acids)-233(from)-233(myocytes.)]TJ
26.2 66.4619 TD
[(FOP)-545(uptake)-582(kinetics)-582(in)-582(liver)-582(are)-582(reversible)-582(\(Fig.)-582(5\).)]TJ
-1 -1.2099 TD
[(Consequently)65(,)-376(the)-376(most)-376(appropriate)-376(index)-376(of)-376(FOP)-339(kinetics)]TJ
T*
[(for)-258(assessment)-258(of)-258(HMF)74(AO)-258(appears)-258(to)-258(be)-258(equilibrium)-258(DV)-240(of)]TJ
T*
[(the)-372(tracer)-372(in)-372(liver)55(.)-372(D)0(V)-354(i)0(s)-372(equivalent)-372(to)-372(the)-372(liver)20(-to-plasma)]TJ
T*
-0.002 Tc
[(radioactivity)-198(concentration)-198(ratio)-198(at)-198(equilibrium)-198(if)-198(the)-198(concen-)]TJ
T*
0 Tc
[(trations)-540(of)-540(radiolabeled)-540(compounds)-540(in)-540(both)-540(arterial)-540(and)]TJ
T*
[(venous)-376(plasma)-376(are)-376(equal)-376(and)-376(the)-376(presence)-376(of)-376(radiolabeled)]TJ
T*
[(metabolites)-509(other)-509(than)-509(FOP)-472(in)-509(plasma)-509(are)-509(negligible.)-509(If)]TJ
T*
[(radiolabeled)-251(metabolites)-251(are)-251(present)-251(in)-251(the)-251(plasma)-251(in)-251(human)]TJ
T*
[(studies,)-325(then)-325(their)-325(potential)-325(uptake)-325(by)-325(liver)-325(will)-325(need)-325(to)-325(be)]TJ
T*
[(characterized)-482(and)-482(accounted)-482(for)55(.)-482(Liver)20(-to-blood)-482(ratios)-482(of)]TJ
T*
[(FOP)-378(showed)-415(good)-415(sensitivity)-415(to)-415(impairment)-415(of)-415(fatty)-415(acid)]TJ
T*
[(oxidation)-410(by)-410(CPT)92(-I)-410(inhibition)-410(in)-410(living)-410(rats.)-410(Furthermore,)]TJ
T*
[(experiments)-555(in)-555(isolated)-555(rat)-555(liver)-555(showed)-555(DV)-537(estimates,)]TJ
T*
[(particularly)-363(of)-363(the)-363(slower)-363(turnover)-363(compartment)-363(\(DV)]TJ
6.486 0 0 6.486 530.524 574.007 Tm
(2)Tj
9.978 0 0 9.978 533.767 575.753 Tm
[(\),)-363(to)]TJ
-22.2771 -1.2099 TD
[(track)-277(the)-277(fatty)-277(acid)-277(oxidation)-277(rate)-277(in)-277(the)-277(liver)55(.)-259(The)-277(measure-)]TJ
T*
[(ment)-326(of)-326(the)-326(tissue-to-blood)-326(\(or)-326(tissue-to-plasma\))-326(ratio)-326(with)]TJ
T*
[(FOP)-338(in)-375(humans)-375(with)-375(PET)-357(would)-375(be)-375(straightforward)-375(using)]TJ
T*
[(images)-235(of)-235(the)-235(liver)-235(and)-235(arterial)-235(blood)-235(concentration)-235(from)-235(the)]TJ
T*
[(left)-537(ventricular)-537(blood)-537(pool)-537(after)-537(equilibrium)-537(is)-537(reached.)]TJ
T*
[(Because)-439(of)-439(the)-439(slow)-439(metabolism)-439(of)-439(the)-439(tracer)-439(relative)-439(to)]TJ
T*
[(circulatory)-328(turnover)40(,)-328(venous)-328(blood)-328(samples)-328(could)-328(likely)-328(be)]TJ
T*
[(used)-263(for)-263(measurements)-263(of)-263(nonmetabolized)-263(fraction)-263(of)-263(tracer)]TJ
T*
[(in)-311(the)-311(plasma.)-311(Use)-311(of)-311(a)-311(tissue-to-blood)-311(ratio)-311(as)-311(an)-311(index)-311(of)]TJ
T*
[(HMF)74(AO)-281(would)-281(obviate)-281(tracer)-281(kinetic)-281(modeling)-281(of)-281(dynamic)]TJ
T*
[(PET)-235(image)-253(data)-253(for)-253(estimation)-253(of)-253(rate)-253(constants.)-198(A)-198(compart-)]TJ
T*
[(mental)-418(model\261based)-418(technique)-418(would)-418(be)-418(complicated)-418(be-)]TJ
T*
[(cause)-591(the)-591(liver)-591(has)-591(both)-591(arterial)-591(and)-591(venous)-591(perfusion)]TJ
T*
[(sources)-333(in)-333(vivo)-333(that)-333(are)-333(distributed)-333(in)-333(di)12(f)25(ferent)-333(proportions)]TJ
T*
[(over)-646(the)-646(entire)-646(liver)55(.)-646(However)40(,)-646(the)-646(model-independent)]TJ
T*
[(tissue-to-blood)-306(ratio)-306(cannot)-306(distinguish)-306(the)-306(contributions)-306(to)]TJ
T*
[(the)-534(DV)-516(of)-534(kinetically)-534(distinct)-534(compartments,)-534(as)-534(can)-534(be)]TJ
T*
[(accomplished)-233(with)-233(the)-233(isolated)-233(rat)-233(liver)-233(model.)]TJ
1 -1.2099 TD
[(The)-334(correspondence)-334(of)-334(the)-334(2)-334(compartments)-334(in)-334(the)-334(tracer)]TJ
-1 -1.2099 TD
[(kinetic)-283(model)-283(to)-283(transport)-283(and)-283(metabolic)-283(processes)-283(for)-283(FOP)]TJ
T*
[(in)-215(liver)-215(has)-215(not)-215(been)-215(clari\256ed.)-215(Because)-215(the)-215(3-oxa)-215(fatty)-215(acid)-215(is)]TJ
T*
[(not)-663(a)-663(substrate)-663(for)]TJ
/F4 1 Tf
9.0961 0 TD
(b)Tj
/F11 1 Tf
0.611 0 TD
[(-oxidation,)-663(the)-663(primary)-663(expected)]TJ
-9.707 -1.2099 TD
[(radiolabeled)-200(metabolites)-200(of)-200(FOP)-163(in)-200(liver)-200(are)-200(the)-200(esteri\256cation)]TJ
T*
[(products\320FOP-CoA)-238(and)-293(FOP-carnitine\320and)-293(complex)-293(lip-)]TJ
T*
[(ids,)-401(whereas)-401([)]TJ
6.486 0 0 6.486 369.634 276.928 Tm
(18)Tj
9.978 0 0 9.978 376.119 273.934 Tm
[(F]\257uoride)-401(may)-401(be)-401(produced)-401(as)-401(a)-401(result)-401(of)]TJ
-6.4774 -1.2099 TD
(microsomal)Tj
/F4 1 Tf
5.2269 0 TD
(v)Tj
/F11 1 Tf
0.667 0 TD
[(-oxidation)-505(\()]TJ
/F12 1 Tf
4.9489 0 TD
(19)Tj
/F11 1 Tf
0.9999 0 TD
[(\).)-450(Another)-505(possibility)-505(is)-505(that)]TJ
-11.8426 -1.2099 TD
(peroxisomal)Tj
/F4 1 Tf
5.3557 0 TD
(a)Tj
/F11 1 Tf
0.611 0 TD
[(-oxidation)-412(\()]TJ
/F12 1 Tf
4.8557 0 TD
(20)Tj
/F11 1 Tf
0.9999 0 TD
[(\))-412(o)0(r)-412(microsomal)-412(peroxidation)]TJ
-11.8223 -1.2099 TD
(\()Tj
/F12 1 Tf
0.333 0 TD
(27)Tj
/F11 1 Tf
0.9999 0 TD
[(\))-217(o)0(f)-217(the)-217(tracer)-217(may)-217(occur)-217(slowly)-217(over)-217(time.)-199(The)-217(\256nding)-217(of)]TJ
-1.3329 -1.2099 TD
[(nearly)-260(all)-260(the)-260(radioactivity)-260(in)-260(the)-260(or)18(ganic-soluble)-260(fraction)-260(of)]TJ
T*
[(liver)-387(extracts)-387(shows)-387(that)-387(FOP)-350(is)-387(not)-387(signi\256cantly)-387(metabo-)]TJ
T*
[(lized)-339(to)-339(hydrophilic)-339(metabolites.)-284(Although)-339(slow)-339(accumula-)]TJ
0 -1.2 TD
[(tion)-378(of)-378(radioactivity)-378(was)-378(observed)-378(in)-378(bone)-378(of)-378(the)-378(rat)-378(with)]TJ
T*
[(FOP)111(,)-386(w)0(e)-386(have)-386(observed)-386(bone)-386(uptake)-386(of)-386(radioactivity)-386(with)]TJ
T*
[(neither)-527(FTP)-490(\()]TJ
/F12 1 Tf
5.8498 0 TD
(9)Tj
/F11 1 Tf
0.5 0 TD
[(\))-527(nor)-527(FOP)-490(in)-527(humans)-527(\(unpublished)-527(data,)]TJ
-6.3498 -1.2 TD
[(1999\).)-347(These)-364(data)-364(suggest)-364(that)-364(the)]TJ
/F4 1 Tf
14.5274 0 TD
(v)Tj
/F11 1 Tf
0.667 0 TD
[(-oxidative)-364(de\257uorina-)]TJ
-15.1943 -1.2 TD
[(tion)-360(of)]TJ
/F4 1 Tf
3.1099 0 TD
(v)Tj
/F11 1 Tf
0.667 0 TD
(-[)Tj
6.486 0 0 6.486 355.818 144.624 Tm
(18)Tj
9.978 0 0 9.978 362.304 141.63 Tm
[(F]\257uoro\261fatty)-360(acid)-360(tracers)-360(apparent)-360(in)-360(rodents)]TJ
-5.0928 -1.2 TD
(\()Tj
/F12 1 Tf
0.333 0 TD
(19)Tj
/F11 1 Tf
0.9999 0 TD
[(\))-476(i)0(s)-476(a)0(n)-476(insigni\256cant)-476(process)-476(in)-476(humans.)-476(Clearance)-476(of)]TJ
-1.3329 -1.2 TD
[(radiolabeled)-279(metabolites)-279(produced)-279(in)-279(liver)-279(and)-279(other)-279(tissues)]TJ
T*
[(could)-328(explain)-328(the)-328(presence)-328(of)-328(metabolites)-328(in)-328(blood)-328(and)-328(the)]TJ
T*
[(decline)-233(of)-233(the)-233(liver)20(-to-blood)-233(ratio)-233(over)-233(time.)]TJ
1 -1.2 TD
[(If)-268(present)-268(in)-268(rat)-268(liver)-268(homogenates,)-268(the)-268(CoA)-213(ester)-268(of)-268(FOP)]TJ
/F14 1 Tf
8.98 0 0 8.98 161.532 745.466 Tm
[(T)74(ABLE)-249(4)]TJ
/F13 1 Tf
-10.7778 -1.2222 TD
[(HPLC)-194(Analysis)-249(of)-249(E)7(f)15(f)15(luent)-249(Samples)-249(from)-249(Isolated)-249(Rat)-249(Liver)]TJ
10.7683 -1.2222 TD
[(with)-249(FOP)]TJ
ET
0 0 0 1 K
0 J 0 j 0.249 w 10 M []0 d
1 i
60.043 715.17 m
299.511 715.17 l
S
1.996 w
60.043 688.104 m
299.511 688.104 l
S
BT
7.982 0 0 7.982 85.422 694.091 Tm
(Group)Tj
6.5142 1.25 TD
[(Intact)-249(FOP)]TJ
1.5984 -1.25 TD
(\(%\))Tj
6.0419 1.25 TD
(Eluted)Tj
-2.0401 -1.25 TD
[(metabolites)-249(\(%\))]TJ
8.9563 1.25 TD
(Retained)Tj
-1.457 -1.25 TD
[(metabolites)-249(\(%\))]TJ
-22.5007 -2.125 TD
[(Normoxic)-249(\(n)]TJ
/F4 1 Tf
5.6378 0 TD
(5)Tj
/F13 1 Tf
1.111 0 TD
(3\))Tj
-5.7488 -1.25 TD
[(Early)-249(\(0.5\2612)-249(min\))-582(69.0)]TJ
/F4 1 Tf
10.3609 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(10.3)-1401(30.5)]TJ
/F4 1 Tf
5.5708 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(9.7)-3469(0.5)]TJ
/F4 1 Tf
6.5266 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
(2.2)Tj
-25.7913 -1.25 TD
[(Late)-249(\(1)74(1\26113)-249(min\))-710(66.0)]TJ
/F4 1 Tf
10.3609 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(14.1)-1401(20.2)]TJ
/F4 1 Tf
5.5708 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(13.3)-2357(13.8)]TJ
/F4 1 Tf
6.5268 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
(1.2*)Tj
-26.7915 -1.25 TD
[(Hypoxic)-249(\(n)]TJ
/F4 1 Tf
4.9719 0 TD
(5)Tj
/F13 1 Tf
1.111 0 TD
(3\))Tj
-5.0829 -1.25 TD
[(Early)-249(\(0.5\2612)-249(min\))-582(91.4)]TJ
/F4 1 Tf
10.3609 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(1.0\262)-1957(9.1)]TJ
/F4 1 Tf
5.5707 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
(1.7\262)Tj
/F4 1 Tf
4.0262 0 TD
(2)Tj
/F13 1 Tf
0.8329 0 TD
(0.5)Tj
/F4 1 Tf
1.6679 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
(2.1)Tj
-25.7915 -1.25 TD
[(Late)-249(\(1)74(1\26113)-249(min\))-710(89.7)]TJ
/F4 1 Tf
10.3609 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(5.6\262)-1957(8.8)]TJ
/F4 1 Tf
5.5707 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
[(4.8\262)-2913(1.0)]TJ
/F4 1 Tf
6.5268 0 TD
(6)Tj
/F13 1 Tf
1.111 0 TD
(2.3\262)Tj
ET
0.249 w
60.043 611.15 m
95.964 611.15 l
S
BT
7.982 0 0 7.982 70.021 600.333 Tm
(*)Tj
7.982 0 1.697 7.982 73.126 600.333 Tm
(P)Tj
/F4 1 Tf
7.982 0 0 7.982 80.307 600.333 Tm
(,)Tj
/F13 1 Tf
1.0655 0 TD
[(0.0001)-233(vs.)-233(early)-233(phase.)]TJ
-2.354 -1.25 TD
(\262)Tj
7.982 0 1.697 7.982 74.459 590.355 Tm
(P)Tj
/F4 1 Tf
7.982 0 0 7.982 81.64 590.355 Tm
(,)Tj
/F13 1 Tf
1.0655 0 TD
[(0.01)-233(vs.)-233(normoxic.)]TJ
-2.521 -1.25 TD
[(FOP)-363(was)-380(administered)-380(to)-380(livers)-380(as)-380(bolus.)-380(E)7(f)15(f)15(luent)-380(was)-380(sampled)]TJ
-1.25 -1.25 TD
[(during)-630(washout)-630(of)-630(radioactivity)-630(from)-630(livers)-630(over)-630(early)-630(and)-630(late)]TJ
T*
[(intervals)-306(given)-306(in)-306(table.)-306(HPLC)-306(conditions)-306(were)-306(as)-306(given)-306(in)-306(Materials)]TJ
T*
[(and)-218(Methods.)-218(Fractions)-218(of)-218(radioactivity)-218(as)-218(intact)-218(FOP)129(,)-218(eluted)-218(metabo-)]TJ
T*
[(lites,)-352(and)-352(metabolites)-352(retained)-352(on)-352(C-18)-352(HPLC)-352(column)-352(\(obtained)-352(by)]TJ
T*
[(balance)-233(of)-233(\256rst)-233(2\))-233(are)-233(given.)]TJ
ET
60.043 525.373 m
299.514 525.373 l
S
BT
/F15 1 Tf
10.477 0 0 10.477 60.043 45.774 Tm
(1734)Tj
/F11 1 Tf
3.6191 0 TD
(T)Tj
7.838 0 0 7.838 104.362 45.774 Tm
(HE)Tj
10.477 0 0 10.477 118.644 45.774 Tm
(J)Tj
7.838 0 0 7.838 122.72 45.774 Tm
[(OURNAL)-489(OF)]TJ
10.477 0 0 10.477 173.054 45.774 Tm
(N)Tj
7.838 0 0 7.838 180.619 45.774 Tm
(UCLEAR)Tj
10.477 0 0 10.477 215.802 45.774 Tm
(M)Tj
7.838 0 0 7.838 225.116 45.774 Tm
(EDICINE)Tj
/F16 1 Tf
10.477 0 0 10.477 261.695 45.774 Tm
(x)Tj
/F11 1 Tf
0.778 0 TD
[(V)129(ol.)-366(41)]TJ
/F16 1 Tf
3.4874 0 TD
(x)Tj
/F11 1 Tf
0.778 0 TD
[(No.)-366(10)]TJ
/F16 1 Tf
3.3382 0 TD
(x)Tj
/F11 1 Tf
0.778 0 TD
[(October)-366(2000)]TJ
ET
endstream
endobj
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T*
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[(oxidative)-223(metabolism)-223(of)-223(exogenous)-223(long-chain)-223(fatty)-223(acids)-223(in)]TJ
T*
[(liver)-426(using)-426(facile)-426(measurements)-426(of)-426(its)-426(equilibrium)-426(DV)-408(in)]TJ
T*
[(tissue)-478(\(tissue-to-blood)-478(ratio\).)-478(Hepatic)-478(uptake)-478(kinetics)-478(are)]TJ
T*
[(relatively)-589(rapid)-589(and)-589(reversible.)-571(The)-589(equilibrium)-589(DV)-571(in)]TJ
T*
[(isolated)-347(rat)-347(liver)-347(tracks)-347(the)-347(decrease)-347(in)]TJ
/F4 1 Tf
16.2544 0 TD
0 Tw
(b)Tj
/F11 1 Tf
0.611 0 TD
[(-oxidation)-347(rate)-347(of)]TJ
-16.8654 -1.2 TD
[(exogenous)-412(palmitate)-412(induced)-412(by)-412(hypoxia.)-412(FOP)-376(under)18(goes)]TJ
T*
[(slow)-229(metabolism)-229(in)-229(the)-229(rat)-229(to)-229(unidenti\256ed)-229(polar)-229(lipid)-229(species)]TJ
T*
[(and)-264(free)-264([)]TJ
6.486 0 0 6.486 98.539 514.281 Tm
(18)Tj
9.978 0 0 9.978 105.025 511.288 Tm
[(F]\257uoride.)-264(Further)-264(studies)-264(are)-264(required)-264(to)-264(clarify)]TJ
-4.5081 -1.2 TD
[(the)-529(biochemical)-529(fate)-529(of)-529(FOP)-492(in)-529(liver)-529(and)-529(determine)-529(its)]TJ
T*
[(general)-233(applicability)-233(as)-233(a)-233(PET)-215(probe)-233(of)-233(regional)-233(HMF)74(AO.)]TJ
/F14 1 Tf
8.98 0 0 8.98 60.043 461.095 Tm
(ACKNOWLEDGMENTS)Tj
/F11 1 Tf
9.978 0 0 9.978 70.021 445.433 Tm
[(This)-535(study)-535(was)-535(supported)-535(by)-535(grant)-535(HL-54882)-535(of)-535(the)]TJ
-1 -1.2 TD
[(National)-291(Institutes)-291(of)-291(Health,)-291(Bethesda,)-291(MD.)-291(Etomoxir)-291(was)]TJ
T*
[(generously)-648(provided)-648(by)-648(Dr)55(.)-648(H)0(.)-630(W)80(olf)-648(of)-648(Byk)-648(Gulden,)]TJ
T*
[(Konstanz,)-233(Germany)65(.)]TJ
/F14 1 Tf
9.479 0 0 9.479 60.043 383.868 Tm
(REFERENCES)Tj
/F11 1 Tf
6.985 0 0 6.985 63.536 370.287 Tm
[(1.)-500(Eaton)-253(S,)-253(Record)-253(CO,)-253(Bartlett)-253(K.)-253(Multiple)-253(biochemical)-253(e)12(f)25(fects)-253(in)-253(the)-253(pathogenesis)]TJ
1.25 -1.2857 TD
[(of)-233(alcoholic)-233(fatty)-233(liver)55(.)]TJ
/F12 1 Tf
9.2931 0 TD
[(Eur)-233(J)-233(Clin)-233(Invest.)]TJ
/F11 1 Tf
7.2376 0 TD
(1997;27:719\261722.)Tj
-17.7808 -1.2857 TD
[(2.)-500(Sheth)-296(SG,)-296(Gordon)-296(FD,)-296(Chopra)-296(S.)-296(Nonalcoholic)-296(steatohepatitis.)]TJ
/F12 1 Tf
27.119 0 TD
[(Ann)-296(Intern)-296(Med.)]TJ
/F11 1 Tf
-25.869 -1.2857 TD
(1997;126:137\261145.)Tj
-1.25 -1.2857 TD
[(3.)-500(Kahler)-469(A,)-524(Zimmermann)-524(M,)-524(Langhans)-506(W)92(.)-524(Suppression)-524(of)-524(hepatic)-524(fatty)-524(acid)]TJ
1.25 -1.2857 TD
[(oxidation)-233(and)-233(food)-233(intake)-233(in)-233(men.)]TJ
/F12 1 Tf
13.6483 0 TD
(Nutrition.)Tj
/F11 1 Tf
4.1515 0 TD
(1999;15:819\261828.)Tj
-19.0498 -1.2857 TD
[(4.)-500(Scharrer)-499(E.)-499(Control)-499(of)-499(food)-499(intake)-499(by)-499(fatty)-499(acid)-499(oxidation)-499(and)-499(ketogenesis.)]TJ
/F12 1 Tf
1.25 -1.2857 TD
(Nutrition.)Tj
/F11 1 Tf
4.1515 0 TD
(1999;15:704\261714.)Tj
-5.4015 -1.2857 TD
[(5.)-500(Sidossis)-351(LS,)-351(Mittendorfer)-351(B,)-333(W)80(alser)-351(E,)-351(Chinkes)-351(D,)-333(W)80(olfe)-351(RR.)-351(Hyper)18(glycemia-)]TJ
1.25 -1.2857 TD
[(induced)-214(inhibition)-214(of)-214(splanchnic)-214(fatty)-214(acid)-214(oxidation)-214(increases)-214(hepatic)-214(triacylglyc-)]TJ
T*
[(erol)-233(secretion.)]TJ
/F12 1 Tf
5.8816 0 TD
[(Am)-233(J)-233(Physiol.)]TJ
/F11 1 Tf
5.7265 0 TD
(1998;E798\261E805.)Tj
-12.8581 -1.2857 TD
[(6.)-500(Randle)-332(PJ,)-332(Priestman)-332(DA,)-332(Mistry)-332(S,)-332(Halsall)-277(A.)-332(Mechanisms)-332(modifying)-332(glucose)]TJ
1.25 -1.2857 TD
[(oxidation)-233(in)-233(diabetes)-233(mellitus.)]TJ
/F12 1 Tf
12.2393 0 TD
(Diabetologia.)Tj
/F11 1 Tf
5.7617 0 TD
[(1994;37\(suppl)-233(2\):S155\261S161.)]TJ
-19.251 -1.2857 TD
[(7.)-500(Y)100(amamura)-203(N,)-203(Magata)-166(Y)129(,)-203(Kitano)-203(H,)-203(Konishi)-203(J,)-203(Saji)-203(H.)-203(Evaluation)-203(of)-203([1-)]TJ
4.49 0 0 4.49 267.303 255.54 Tm
-0.037 Tc
(11)Tj
6.985 0 0 6.985 271.629 253.545 Tm
0 Tc
(C]octano-)Tj
-28.5432 -1.2857 TD
[(ate)-477(as)-477(a)-477(new)-477(radiopharmaceutical)-476(for)-477(assessing)-477(liver)-477(function)-477(using)-477(positron)]TJ
T*
[(emission)-233(tomography)65(.)]TJ
/F12 1 Tf
9.0411 0 TD
[(Nucl)-233(Med)-233(Biol.)]TJ
/F11 1 Tf
6.2826 0 TD
(1998;25:467\261472.)Tj
-16.5737 -1.2857 TD
[(8.)-500(Kawashima)-423(H,)-423(Kuge)-386(Y)129(,)-386(Y)100(ajima)-423(K,)-423(Miyake)-386(Y)129(,)-423(Hashimoto)-423(N.)-423(Development)-423(of)]TJ
1.25 -1.2857 TD
[(step-speci\256c)-365(PET)-347(tracers)-365(for)-364(studying)-365(fatty)-365(acid)]TJ
/F4 1 Tf
20.0876 0 TD
(b)Tj
/F11 1 Tf
0.6111 0 TD
[(-oxidation:)-364(biodistribution)-365(of)]TJ
-20.6986 -1.2857 TD
([1-)Tj
4.49 0 0 4.49 80.412 210.64 Tm
-0.037 Tc
(11)Tj
6.985 0 0 6.985 84.737 208.644 Tm
0 Tc
[(C]octanoate)-233(analogs)-233(in)-233(rats)-233(and)-233(a)-233(cat.)]TJ
/F12 1 Tf
15.0454 0 TD
[(Nucl)-233(Med)-233(Biol.)]TJ
/F11 1 Tf
6.2826 0 TD
(1998;25:543\261548.)Tj
-24.3634 -1.2857 TD
[(9.)-500(DeGrado)-244(TR,)-244(W)80(ang)-261(S.)-207(An)-261(F-18)-261(labeled)-261(probe)-261(of)-261(fatty)-261(acid)-261(oxidation)-261(for)-261(use)-261(with)]TJ
1.25 -1.2857 TD
[(positron)-233(emission)-233(tomography)-233(\(PET\))-233([abstract].)]TJ
/F12 1 Tf
19.3041 0 TD
[(F)129(ASEB)-233(J.)]TJ
/F11 1 Tf
3.9757 0 TD
(1999;13:A764.)Tj
-25.0299 -1.2857 TD
[(10.)-500(DeGrado)-575(TR,)-575(W)80(ang)-593(S,)-593(Holden)-593(JE,)-593(Nickles)-593(RJ,)-593(Stone)-593(CK.)-593(Synthesis)-593(and)]TJ
1.75 -1.2857 TD
[(preliminary)-625(evaluation)-625(of)]TJ
4.49 0 0 4.49 152.877 174.719 Tm
(18)Tj
6.985 0 0 6.985 157.367 172.723 Tm
[(F-labeled)-625(4-thia)-625(palmitate)-625(as)-625(a)-625(PET)-607(tracer)-625(of)]TJ
-12.1841 -1.2857 TD
[(myocardial)-233(fatty)-233(acid)-233(oxidation.)]TJ
/F12 1 Tf
12.9594 0 TD
[(Nucl)-233(Med)-233(Biol.)]TJ
/F11 1 Tf
6.2826 0 TD
(2000;27:221\261231.)Tj
-20.992 -1.2857 TD
[(1)37(1)0(.)-500(DeGrado)-349(TR,)-349(W)80(ang)-367(S,)-367(Rockey)-367(DC.)-367(Evaluation)-367(of)]TJ
4.49 0 0 4.49 219.189 156.759 Tm
(18)Tj
6.985 0 0 6.985 223.678 154.763 Tm
[(F-labeled)-367(16-\257uoro-4-thia-)]TJ
-21.715 -1.2857 TD
[(palmitate)-281(\(FTP\))-281(as)-281(a)-281(PET)-263(tracer)-281(for)]TJ
/F4 1 Tf
14.5605 0 TD
(b)Tj
/F11 1 Tf
0.6111 0 TD
[(-oxidation)-281(of)-281(long-chain)-281(fatty)-281(acids)-281(in)-281(liver)]TJ
-15.1716 -1.2857 TD
([abstract].)Tj
/F12 1 Tf
4.2595 0 TD
[(J)-233(Nucl)-233(Med.)]TJ
/F11 1 Tf
5.0594 0 TD
[(1999;40\(suppl\):124P)111(.)]TJ
24.968 87.3572 TD
[(12.)-500(Skorve)-209(J,)-154(Asiedu)-209(D,)-209(Solbakken)-209(M,)-209(Gjestdal)-209(J,)-209(Songstad)-209(J,)-209(Ber)18(ge)-209(RK.)-209(Comparative)]TJ
1.75 -1.3567 TD
[(e)12(f)25(fects)-237(of)-237(oxygen)-237(and)-237(sulfur)20(-substituted)-237(fatty)-237(acids)-237(on)-237(serum)-238(lipids)-237(and)-237(mitochon-)]TJ
T*
[(drial)-321(and)-321(peroxisomal)-321(fatty)-321(acid)-321(oxidation)-321(in)-321(rat.)]TJ
/F12 1 Tf
20.1482 0 TD
[(Biochem)-321(Pharmacol.)]TJ
/F11 1 Tf
8.8353 0 TD
(1992;43:)Tj
-28.9835 -1.3567 TD
(815\261822.)Tj
-1.75 -1.3567 TD
[(13.)-500(Sonnet)-304(PE,)-304(Proveaux)-249(A)111(T)74(,)-249(Adamek)-304(E,)-304(Sugie)-304(H,)-304(Sato)-304(R,)-286(T)70(amaki)-267(Y)129(.)-304(Stereoisomers)]TJ
1.75 -1.3567 TD
[(and)-233(analogs)-233(of)-233(14-methyl-1-octadecene,)-233(sex)-233(pheromone)-233(of)-233(peach)-233(leafminer)-233(moth,)]TJ
/F12 1 Tf
T*
[(L)30(yonetia)-233(clerkella)]TJ
/F11 1 Tf
7.2032 0 TD
0.233 Tc
[(,L)233(.)]TJ
/F12 1 Tf
1.5771 0 TD
0 Tc
[(J)-233(Chem)-233(Ecol.)]TJ
/F11 1 Tf
5.5595 0 TD
(1987;13:547\261555.)Tj
-16.0898 -1.3425 TD
[(14.)-500(Nagatsugi)-253(F)80(,)-253(Sasaki)-253(S,)-253(Maeda)-253(M.)-253(Synthesis)-253(of)]TJ
/F4 1 Tf
20.5034 0 TD
(v)Tj
/F11 1 Tf
0.6671 0 TD
[(-\257uorinated)-253(octanoic)-253(acid)-253(and)-253(its)]TJ
/F4 1 Tf
-19.4205 -1.3425 TD
(b)Tj
/F11 1 Tf
0.6111 0 TD
[(-substituted)-233(derivatives.)]TJ
/F12 1 Tf
9.7721 0 TD
[(J)-233(Fluorine)-233(Chem.)]TJ
/F11 1 Tf
7.2267 0 TD
(1992;56:373\261383.)Tj
-19.3599 -1.3425 TD
-0.002 Tc
[(15.)-499(DeGrado)-181(TR.)-198(Synthesis)-198(of)-198(14\(R,S\)-[)]TJ
4.49 0 0 4.49 424.191 663.962 Tm
(18)Tj
6.985 0 0 6.985 428.659 661.966 Tm
[(F]\257uoro-6-thia-heptadecanoic)-198(acid)-199(\(FTHA\).)]TJ
/F12 1 Tf
-15.0257 -1.3425 TD
0 Tc
[(J)-233(Label)-233(Comp)-233(Radiopharm.)]TJ
/F11 1 Tf
11.2942 0 TD
(1991;29:989\261995.)Tj
-13.0442 -1.3425 TD
[(16.)-500(Coenen)-456(HH,)-456(Klatte)-456(B,)-456(Knoechel)-401(A,)-456(Shueller)-456(M,)-456(Stoecklin)-456(G.)-456(Preparation)-456(of)]TJ
1.75 -1.3425 TD
[(N.C.A.)-608([17-)]TJ
4.49 0 0 4.49 359.583 635.831 Tm
(18)Tj
6.985 0 0 6.985 364.073 633.835 Tm
[(F]\257uoroheptadecanoic)-608(acid)-608(in)-608(high)-608(yields)-608(via)-608(aminopolyether)]TJ
-5.7788 -1.3425 TD
[(supported,)-367(nucleophilic)-367(\257uorination.)]TJ
/F12 1 Tf
15.1563 0 TD
[(J)-367(Label)-367(Comp)-367(Radiopharm.)]TJ
/F11 1 Tf
11.8283 0 TD
(1986;23:455\261)Tj
-26.9845 -1.3425 TD
(466.)Tj
-1.75 -1.3425 TD
[(17.)-500(DeGrado)-293(TR,)-311(Sto)]TJ
8.4655 0 TD
[(\310)-84(cklin)-311(G,)-311(Coenen)-311(HH.)-311(14\(R,S\)-[)]TJ
4.49 0 0 4.49 462.726 607.7 Tm
(18)Tj
6.985 0 0 6.985 467.216 605.704 Tm
(F]\257uoro-6-thia-heptadecanoic)Tj
-20.546 -1.3425 TD
[(acid)-200(\(FTHA\):)-200(evaluation)-200(in)-200(mouse)-200(of)-200(a)-200(new)-200(in)-200(vivo)-200(probe)-200(of)-200(myocardial)-200(utilization)]TJ
T*
[(of)-233(long-chain)-233(fatty)-233(acids.)]TJ
/F12 1 Tf
10.181 0 TD
[(J)-233(Nucl)-233(Med.)]TJ
/F11 1 Tf
5.0594 0 TD
(1991;32:1888\2611896.)Tj
-16.9905 -1.3425 TD
[(18.)-500(Saddik)-295(M,)-295(Lopaschuk)-295(G.)-295(Myocardial)-295(triglyceride)-295(turnover)-295(during)-295(reperfusion)-295(of)]TJ
1.75 -1.3425 TD
[(isolated)-242(rat)-242(hearts)-242(subjected)-242(to)-242(a)-242(transient)-242(period)-242(of)-242(global)-242(ischemia.)]TJ
/F12 1 Tf
27.3584 0 TD
[(J)-242(Biol)-242(Chem.)]TJ
/F11 1 Tf
-27.3584 -1.3425 TD
(1992;267:3825\2613831.)Tj
-1.75 -1.3425 TD
[(19.)-500(DeGrado)-382(TR,)-400(Moka)-400(DC.)-400(Non-)]TJ
/F4 1 Tf
14.5528 0 TD
(b)Tj
/F11 1 Tf
0.6111 0 TD
(-oxidizable)Tj
/F4 1 Tf
4.8993 0 TD
(v)Tj
/F11 1 Tf
0.6671 0 TD
(-[)Tj
4.49 0 0 4.49 460.932 551.438 Tm
(18)Tj
6.985 0 0 6.985 465.422 549.442 Tm
[(F]\257uoro)-400(long-chain)-400(fatty)-400(acid)]TJ
-20.2892 -1.3425 TD
[(analogs)-422(show)-422(cytochrome)-422(P-450)-422(mediated)-422(de\257uorination:)-422(implications)-422(for)-422(the)]TJ
T*
[(design)-541(of)-541(PET)-523(tracers)-541(of)-541(myocardial)-541(fatty)-541(acid)-541(utilization.)]TJ
/F12 1 Tf
25.8741 0 TD
[(Nucl)-541(Med)-541(Biol.)]TJ
/F11 1 Tf
-25.8741 -1.3425 TD
(1992;19:389\261397.)Tj
-1.75 -1.3425 TD
[(20.)-500(Mihalik)-265(SJ,)-265(Rainville)-211(AM,)-248(W)80(atkins)-265(P)92(A)0(.)-265(Phytanic)-265(acid)-265(alpha-oxidation)-265(in)-265(rat)-265(liver)]TJ
1.75 -1.3425 TD
[(peroxisomes:)-506(production)-506(of)-506(alpha-hydroxyphytanoyl-CoA)-451(and)-506(formate)-506(is)-506(en-)]TJ
T*
[(hanced)-233(by)-233(dioxygenase)-233(cofactors.)]TJ
/F12 1 Tf
13.6795 0 TD
[(Eur)-233(J)-233(Biochem.)]TJ
/F11 1 Tf
6.3926 0 TD
(1995;232:545\26151.)Tj
-21.8221 -1.3425 TD
[(21.)-500(Marquardt)-388(DW)92(.)-334(A)0(n)-388(algorithm)-388(for)-388(least-squares)-388(estimation)-388(of)-388(nonlinear)-388(param-)]TJ
1.75 -1.3425 TD
(eters.)Tj
/F12 1 Tf
2.3712 0 TD
[(J)-233(Soc)-233(Ind)-215(Appl)-233(Math.)]TJ
/F11 1 Tf
8.6189 0 TD
[(1963;1)37(1:431\261441.)]TJ
-12.7401 -1.3425 TD
[(22.)-500(W)40(illiamson)-387(JR,)-387(Scholz)-387(R,)-387(Browning)-387(ET)74(,)-387(e)0(t)-387(al.)-387(Metabolic)-387(e)12(f)25(fects)-387(of)-387(ethanol)-387(in)]TJ
1.75 -1.3425 TD
[(perfused)-233(rat)-233(liver)55(.)]TJ
/F12 1 Tf
7.2259 0 TD
[(J)-233(Biol)-233(Chem.)]TJ
/F11 1 Tf
5.3935 0 TD
(1969;244:5044\2615054.)Tj
-14.3694 -1.3425 TD
[(23.)-500(Cederbaum)-153(AI,)-208(Lieber)-208(CS,)-208(Beattie)-208(DS,)-208(et)-208(al.)-208(E)12(f)25(fect)-208(of)-208(chronic)-208(ethanol)-208(ingestion)-208(on)]TJ
1.75 -1.3425 TD
[(fatty)-254(acid)-254(oxidation)-254(by)-254(hepatic)-254(mitochondria.)]TJ
/F12 1 Tf
18.2745 0 TD
[(J)-254(Biol)-254(Chem.)]TJ
/F11 1 Tf
5.4568 0 TD
(1975;250:5122\2615129.)Tj
-25.4813 -1.3425 TD
[(24.)-500(Aarsland)-365(A,)-420(Ber)18(ge)-420(RK.)-420(Peroxisome)-420(proliferating)-420(sulphur)20(-)-420(and)-420(oxy-substituted)]TJ
1.75 -1.3425 TD
[(fatty)-552(acid)-552(analogues)-552(are)-552(activated)-552(to)-552(acyl)-552(coenzyme)-497(A)-497(thioesters.)]TJ
/F12 1 Tf
29.0409 0 TD
(Biochem)Tj
-29.0409 -1.3425 TD
(Pharmacol.)Tj
/F11 1 Tf
4.9276 0 TD
(1991;41:53\26161.)Tj
-6.6776 -1.3425 TD
[(25.)-500(Elmaleh)-221(DR,)-221(Livni)-221(E,)-221(Levy)-221(S,)-203(V)111(arnum)-221(D,)-221(Strauss)-221(HW)92(,)-221(Brownell)-221(GL.)-221(Comparison)]TJ
1.75 -1.3425 TD
(of)Tj
4.49 0 0 4.49 331.083 392.029 Tm
-0.037 Tc
(11)Tj
6.985 0 0 6.985 335.409 390.033 Tm
0 Tc
[(C)-222(and)]TJ
4.49 0 0 4.49 353.262 392.029 Tm
(14)Tj
6.985 0 0 6.985 357.751 390.033 Tm
[(C-labeled)-222(fatty)-222(acids)-222(and)-222(their)]TJ
/F4 1 Tf
12.1665 0 TD
(b)Tj
/F11 1 Tf
0.6111 0 TD
[(-methyl)-222(analogs.)]TJ
/F12 1 Tf
6.8616 0 TD
[(Int)-222(J)-222(Nucl)-222(Med)-222(Biol.)]TJ
/F11 1 Tf
-24.5128 -1.3425 TD
(1983;10:181\261187.)Tj
-1.75 -1.3425 TD
[(26.)-500(W)80(eis)-418(BC,)-418(Cowan)-363(A)111(T)74(,)-418(Brown)-418(N,)-418(Foster)-418(DW)92(,)-418(McGarry)-418(JD.)-418(Use)-418(of)-418(a)-418(selective)]TJ
1.75 -1.3425 TD
[(inhibitor)-267(of)-267(liver)-267(carnitine)-267(palmitoyltransferase)-267(I)-267(\(CPT)-249(I\))-267(allows)-267(quanti\256cation)-267(of)]TJ
T*
[(its)-244(contribution)-244(to)-244(total)-244(CPT)-226(I)-244(activity)-244(in)-244(rat)-244(heart.)]TJ
/F12 1 Tf
20.0585 0 TD
[(J)-244(Biol)-244(Chem.)]TJ
/F11 1 Tf
5.4251 0 TD
(1994;269:26443\261)Tj
-25.4836 -1.3425 TD
(26448.)Tj
-1.75 -1.3425 TD
[(27.)-500(Esterbauer)-281(H,)-281(Benedetti)-226(A,)-281(Lang)-281(J,)-281(Fulceri)-281(R,)-281(Fauler)-281(G,)-281(Comporti)-281(M.)-281(Studies)-281(on)]TJ
1.75 -1.3425 TD
[(the)-581(mechanism)-581(of)-581(formation)-581(of)-581(4-hydroxynonenal)-581(during)-581(microsomal)-581(lipid)]TJ
T*
(peroxidation.)Tj
/F12 1 Tf
5.5386 0 TD
[(Biochim)-233(Biophys)-215(Acta.)]TJ
/F11 1 Tf
9.3201 0 TD
(1986;876:154\261166.)Tj
-16.6088 -1.3425 TD
[(28.)-500(Rosendal)-267(J,)-267(Knudsen)-268(J.)-213(A)-213(fast)-267(and)-268(versatile)-268(method)-268(for)-267(extraction)-268(and)-268(quanti\256ca-)]TJ
1.75 -1.3425 TD
[(tion)-315(of)-315(long-chain)-315(acyl-CoA)-260(esters)-315(from)-315(tissue:)-315(content)-315(of)-315(individual)-315(long-chain)]TJ
T*
[(acyl-CoA)-178(esters)-233(in)-233(various)-233(tissues)-233(from)-233(fed)-233(rat.)]TJ
/F12 1 Tf
18.8911 0 TD
[(Anal)-233(Biochem.)]TJ
/F11 1 Tf
6.1046 0 TD
(1992;207:63\26167.)Tj
-26.7457 -1.3425 TD
[(29.)-500(Pande)-266(SV)129(,)-266(Parvin)-266(R.)-266(Clo\256brate)-266(enhancement)-266(of)-266(mitochondrial)-266(carnitine)-266(transport)]TJ
1.75 -1.3425 TD
[(system)-276(of)-276(rat)-276(liver)-276(and)-276(augmentation)-276(of)-276(liver)-276(carnitine)-276(and)-276(gamma-butyrobetaine)]TJ
T*
[(hydroxylase)-233(activity)-233(by)-233(thyroxine.)]TJ
/F12 1 Tf
13.9045 0 TD
[(Biochim)-233(Biophys)-215(Acta.)]TJ
/F11 1 Tf
9.3201 0 TD
(1980;617:363\26170.)Tj
-24.9746 -1.3425 TD
[(30.)-500(Bhuiyan)-196(AKMJ,)-251(Jackson)-251(S,)-233(T)35(urnbull)-251(DM,)-196(A)92(ynsley-Green)-196(A,)-251(Leonard)-251(JV)129(,)-251(Bartlett)]TJ
1.75 -1.3425 TD
[(K.)-219(The)-237(measurement)-237(of)-237(carnitine)-237(and)-237(acyl-carnitines:)-237(application)-237(to)-237(the)-237(investiga-)]TJ
T*
[(tion)-421(of)-421(patients)-421(with)-421(suspected)-421(inherited)-421(disorders)-421(of)-421(mitochondrial)-421(fatty)-421(acid)]TJ
T*
(oxidation.)Tj
/F12 1 Tf
4.2615 0 TD
[(Clin)-233(Chim)-215(Acta.)]TJ
/F11 1 Tf
6.6548 0 TD
(1992;207:185\261204.)Tj
-12.6663 -1.3425 TD
[(31.)-500(Steinmann)-354(B,)-354(Bachmann)-354(C,)-354(Colombo)-354(JP)111(,)-354(Gitzelmann)-354(R.)-336(The)-354(renal)-354(handling)-354(of)]TJ
1.75 -1.3425 TD
[(carnitine)-495(in)-495(patients)-495(with)-495(selective)-495(tubulopathy)-495(and)-495(with)-495(Fanconi)-495(syndrome.)]TJ
/F12 1 Tf
T*
[(Pediatr)-233(Res.)]TJ
/F11 1 Tf
5.1605 0 TD
(1987;21:201\261204.)Tj
-6.9105 -1.3425 TD
[(32.)-500(Sugimoto)-309(T)74(,)-327(Nishida)-327(N,)-309(W)80(o)0(o)-327(M)0(,)-327(e)0(t)-327(al.)-327(Serum)-327(and)-327(urinary)-327(carnitine)-327(and)-327(or)18(ganic)]TJ
1.75 -1.3425 TD
[(acids)-233(in)-233(Reye)-233(syndrome)-233(and)-233(Reye-like)-233(syndrome.)]TJ
/F12 1 Tf
19.9911 0 TD
[(Brain)-233(Dev)74(.)]TJ
/F11 1 Tf
4.5306 0 TD
(1986;8:257\261261.)Tj
-26.2717 -1.3425 TD
[(33.)-500(W)80(olf)-352(HPO,)-351(Eistetter)-352(K,)-351(Ludwig)-352(G.)-351(Phenylalkyloxirane)-352(carboxylic)-352(acids,)-351(a)-352(new)]TJ
1.75 -1.3425 TD
[(class)-331(of)-331(hypoglycaemic)-331(substances:)-331(hypoglycaemic)-331(and)-331(hypoketonaemic)-331(e)12(f)25(fects)]TJ
T*
[(of)-636(sodium)-636(2-[5-\(4-chlorophenyl\)-pentyl]-oxirane-2-carboxylate)-636(\(B807\26127\))-636(in)]TJ
T*
[(fasted)-233(animals.)]TJ
/F12 1 Tf
6.2157 0 TD
(Diabetologia.)Tj
/F11 1 Tf
5.7617 0 TD
(1982;22:456\261463.)Tj
/F15 1 Tf
10.477 0 0 10.477 60.043 45.774 Tm
(1736)Tj
/F11 1 Tf
3.6191 0 TD
(T)Tj
7.838 0 0 7.838 104.362 45.774 Tm
(HE)Tj
10.477 0 0 10.477 118.644 45.774 Tm
(J)Tj
7.838 0 0 7.838 122.72 45.774 Tm
[(OURNAL)-489(OF)]TJ
10.477 0 0 10.477 173.054 45.774 Tm
(N)Tj
7.838 0 0 7.838 180.619 45.774 Tm
(UCLEAR)Tj
10.477 0 0 10.477 215.802 45.774 Tm
(M)Tj
7.838 0 0 7.838 225.116 45.774 Tm
(EDICINE)Tj
/F16 1 Tf
10.477 0 0 10.477 261.695 45.774 Tm
(x)Tj
/F11 1 Tf
0.778 0 TD
[(V)129(ol.)-366(41)]TJ
/F16 1 Tf
3.4874 0 TD
(x)Tj
/F11 1 Tf
0.778 0 TD
[(No.)-366(10)]TJ
/F16 1 Tf
3.3382 0 TD
(x)Tj
/F11 1 Tf
0.778 0 TD
[(October)-366(2000)]TJ
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