;PMID: 2590949 ;source_file_1902.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..40] = [t:0..40] ;1)sentence:[e:46..162] = [t:46..162] ;2)section:[e:166..238] = [t:166..238] ;3)section:[e:242..330] = [t:242..330] ;4)sentence:[e:334..672] = [t:334..672] ;5)sentence:[e:673..793] = [t:673..793] ;6)sentence:[e:794..887] = [t:794..887] ;7)sentence:[e:888..993] = [t:888..993] ;8)sentence:[e:994..1119] = [t:994..1119] ;9)sentence:[e:1120..1237] = [t:1120..1237] ;10)sentence:[e:1238..1372] = [t:1238..1372] ;11)sentence:[e:1373..1538] = [t:1373..1538] ;12)sentence:[e:1539..1634] = [t:1539..1634] ;13)sentence:[e:1635..1688] = [t:1635..1688] ;14)section:[e:1692..1736] = [t:1692..1736] ;section 0 Span:0..40 ;Chem Phys Lipids. 1989 Oct;51(2):119-26. (SEC (FRAG (NNP:[0..4] Chem) (NNP:[5..9] Phys) (NNP:[10..16] Lipids) (.:[16..17] .) (CD:[18..22] 1989) (CD:[23..28] Oct;5) (CC:[28..30] 1-LRB-) (CD:[30..31] 2) (-RRB-:[31..32] -RRB-) (::[32..33] :) (CD:[33..36] 119) (::[36..37] -) (CD:[37..39] 26) (.:[39..40] .))) ;sentence 1 Span:46..162 ;Effect of natural and structurally modified bile acids on cholesterol ;metabolizing enzymes in rat liver microsomes. ;[90..100]:substance:"bile acids" ;[104..115]:substance:"cholesterol" ;[130..137]:substance:"enzymes" (SENT (NP-HLN (NP (NN:[46..52] Effect)) (PP (IN:[53..55] of) (NP (NP (JJ:[56..63] natural) (NML-1 (-NONE-:[63..63] *P*))) (CC:[64..67] and) (NP (ADJP (RB:[68..80] structurally) (VBN:[81..89] modified)) (NML-1 (NN:[90..94] bile) (NNS:[95..100] acids))))) (PP (IN:[101..103] on) (NP (ADJP (NN:[104..115] cholesterol) (VBG:[117..129] metabolizing)) (NNS:[130..137] enzymes))) (PP-LOC (IN:[138..140] in) (NP (NN:[141..144] rat) (NN:[145..150] liver) (NNS:[151..161] microsomes))) (.:[161..162] .))) ;section 2 Span:166..238 ;Crestani M, De Fabiani E, Malavasi B, Cancellieri M, Galli G, Bosisio E. (SEC (FRAG (NNP:[166..174] Crestani) (NNP:[175..177] M,) (NNP:[178..180] De) (NNP:[181..188] Fabiani) (NNP:[189..190] E) (,:[190..191] ,) (NNP:[192..200] Malavasi) (NNP:[201..202] B) (,:[202..203] ,) (NNP:[204..215] Cancellieri) (NNP:[216..218] M,) (NNP:[219..224] Galli) (NNP:[225..226] G) (,:[226..227] ,) (NNP:[228..235] Bosisio) (NNP:[236..238] E.))) ;section 3 Span:242..330 ;Institute of Pharmacological Sciences, Faculty of Pharmacy, University of ;Milan, Italy. (SEC (FRAG (NNP:[242..251] Institute) (IN:[252..254] of) (NNP:[255..270] Pharmacological) (NNPS:[271..279] Sciences) (,:[279..280] ,) (NNP:[281..288] Faculty) (IN:[289..291] of) (NNP:[292..300] Pharmacy) (,:[300..301] ,) (NNP:[302..312] University) (IN:[313..315] of) (NNP:[316..321] Milan) (,:[321..322] ,) (NNP:[324..329] Italy) (.:[329..330] .))) ;sentence 4 Span:334..672 ;The effect of chenodeoxycholic (CDCA), ursodeoxycholic (UDCA), ;tauroursodeoxycholic (TUDCA), cholic (CA), ursocholic (UCA) acids, analogues ;of CDCA and UDCA with a cyclopropyl ring at C22, C23 (cypro-CDCA and ;cypro-UDCA) and 23-methylursodeoxycholic acid (MUDCA) on cholesterol 7 ;alpha-hydroxylase was studied in rat liver microsomes. ;[348..371]...[458..463]:substance:"chenodeoxycholic (CDCA)"..."acids" ;[373..395]...[458..463]:substance:"ursodeoxycholic (UDCA)"..."acids" ;[398..426]...[458..463]:substance:"tauroursodeoxycholic (TUDCA)"..."acids" ;[428..439]...[458..463]:substance:"cholic (CA)"..."acids" ;[441..463]:substance:"ursocholic (UCA) acids" ;[465..474]:substance:"analogues" ;[479..483]:substance:"CDCA" ;[488..492]:substance:"UDCA" ;[530..540]:substance:"cypro-CDCA" ;[545..555]:substance:"cypro-UDCA" ;[562..591]:substance:"23-methylursodeoxycholic acid" ;[593..598]:substance:"MUDCA" ;[603..634]:cyp450:"cholesterol 7 alpha-hydroxylase" (SENT (S (NP-SBJ-2 (NP (DT:[334..337] The) (NN:[338..344] effect)) (PP (IN:[345..347] of) (NP (NP (NP (NP (ADJP (ADJP (JJ:[348..364] chenodeoxycholic)) (ADJP (-LRB-:[365..366] -LRB-) (NN:[366..370] CDCA) (-RRB-:[370..371] -RRB-))) (NML-1 (-NONE-:[371..371] *P*))) (,:[371..372] ,) (NP (ADJP (ADJP (JJ:[373..388] ursodeoxycholic)) (ADJP (-LRB-:[389..390] -LRB-) (NN:[390..394] UDCA) (-RRB-:[394..395] -RRB-))) (NML-1 (-NONE-:[395..395] *P*))) (,:[395..396] ,) (NP (ADJP (ADJP (JJ:[398..418] tauroursodeoxycholic)) (ADJP (-LRB-:[419..420] -LRB-) (NN:[420..425] TUDCA) (-RRB-:[425..426] -RRB-))) (NML-1 (-NONE-:[426..426] *P*))) (,:[426..427] ,) (NP (ADJP (ADJP (JJ:[428..434] cholic)) (ADJP (-LRB-:[435..436] -LRB-) (NN:[436..438] CA) (-RRB-:[438..439] -RRB-))) (NML-1 (-NONE-:[439..439] *P*))) (,:[439..440] ,) (NP (ADJP (ADJP (JJ:[441..451] ursocholic)) (ADJP (-LRB-:[452..453] -LRB-) (NN:[453..456] UCA) (-RRB-:[456..457] -RRB-))) (NML-1 (NNS:[458..463] acids)))) (,:[463..464] ,) (NP (NP (NNS:[465..474] analogues)) (PP (IN:[475..477] of) (NP (NN:[479..483] CDCA) (CC:[484..487] and) (NN:[488..492] UDCA))) (PP (IN:[493..497] with) (NP (NP (DT:[498..499] a) (NN:[500..511] cyclopropyl) (NN:[512..516] ring)) (PP-LOC (IN:[517..519] at) (NP (NP (NN:[520..523] C22) (,:[523..524] ,) (NN:[525..528] C23)) (NP (-LRB-:[529..530] -LRB-) (NN:[530..540] cypro-CDCA) (CC:[541..544] and) (NN:[545..555] cypro-UDCA) (-RRB-:[555..556] -RRB-)))))))) (CC:[558..561] and) (NP (NP (JJ:[562..586] 23-methylursodeoxycholic) (NN:[587..591] acid)) (NP (-LRB-:[592..593] -LRB-) (NN:[593..598] MUDCA) (-RRB-:[598..599] -RRB-))))) (PP (IN:[600..602] on) (NP (NN:[603..614] cholesterol) (CD:[615..616] 7) (NN:[617..634] alpha-hydroxylase)))) (VP (VBD:[635..638] was) (VP (VBN:[640..647] studied) (NP-2 (-NONE-:[647..647] *)) (PP-LOC (IN:[648..650] in) (NP (NN:[651..654] rat) (NN:[655..660] liver) (NNS:[661..671] microsomes))))) (.:[671..672] .))) ;sentence 5 Span:673..793 ;Cypro-analogues consisted of a mixture of four diasteroisomers, while MUDCA ;was the racemic mixture of two enantiomers. ;[673..688]:substance:"Cypro-analogues" ;[721..736]:substance:"diasteroisomers" ;[744..749]:substance:"MUDCA" ;[758..773]:substance:"racemic mixture" ;[781..792]:substance:"enantiomers" (SENT (S (NP-SBJ (NNS:[673..688] Cypro-analogues)) (VP (VBD:[689..698] consisted) (PP-CLR (IN:[699..701] of) (NP (NP (DT:[702..703] a) (NN:[704..711] mixture)) (PP (IN:[712..714] of) (NP (CD:[715..719] four) (NNS:[721..736] diasteroisomers))))) (,:[736..737] ,) (SBAR-ADV (IN:[738..743] while) (S (NP-SBJ (NN:[744..749] MUDCA)) (VP (VBD:[750..753] was) (NP-PRD (NP (DT:[754..757] the) (JJ:[758..765] racemic) (NN:[766..773] mixture)) (PP (IN:[774..776] of) (NP (CD:[777..780] two) (NNS:[781..792] enantiomers)))))))) (.:[792..793] .))) ;sentence 6 Span:794..887 ;Each steroid was added to liver microsomes at concentrations ranging from 10 ;to 200 microM. ;[800..807]:substance:"steroid" ;[869..871]:quantitative-value:"10" ;[875..878]:quantitative-value:"200" ;[880..886]:quantitative-units:"microM" (SENT (S (NP-SBJ-2 (DT:[794..798] Each) (NN:[800..807] steroid)) (VP (VBD:[808..811] was) (VP (VBN:[812..817] added) (NP-2 (-NONE-:[817..817] *)) (PP-CLR (TO:[818..820] to) (NP (NN:[821..826] liver) (NNS:[827..837] microsomes))) (PP-MNR (IN:[838..840] at) (NP (NP (NNS:[841..855] concentrations)) (VP (VBG:[856..863] ranging) (PP (PP (IN:[864..868] from) (NP (CD:[869..871] 10) (NML-1 (-NONE-:[871..871] *RNR*)))) (PP (TO:[872..874] to) (NP (CD:[875..878] 200) (NML-1 (-NONE-:[878..878] *RNR*)))) (NML-1 (NN:[880..886] microM)))))))) (.:[886..887] .))) ;sentence 7 Span:888..993 ;With the exception of UCA and CA, all the bile acids inhibited cholesterol 7 ;alpha-hydroxylase activity. ;[910..913]:substance:"UCA" ;[918..920]:substance:"CA" ;[930..940]:substance:"bile acids" ;[952..983]:cyp450:"cholesterol 7 alpha-hydroxylase" (SENT (S (PP-1 (IN:[888..892] With) (NP (NP (DT:[893..896] the) (NN:[897..906] exception)) (PP (IN:[907..909] of) (NP (NN:[910..913] UCA) (CC:[914..917] and) (NN:[918..920] CA))))) (,:[920..921] ,) (NP-SBJ (NP (PDT:[922..925] all) (DT:[926..929] the) (NN:[930..934] bile) (NNS:[935..940] acids)) (PP-1 (-NONE-:[940..940] *T*))) (VP (VBD:[941..950] inhibited) (NP (NML (NN:[952..963] cholesterol) (CD:[964..965] 7) (NN:[966..983] alpha-hydroxylase)) (NN:[984..992] activity))) (.:[992..993] .))) ;sentence 8 Span:994..1119 ;The inhibition shown by cypro-CDCA and cypro-UDCA was stronger than that ;observed with the corresponding natural compounds. ;[1018..1028]:substance:"cypro-CDCA" ;[1034..1044]:substance:"cypro-UDCA" ;[1109..1118]:substance:"compounds" (SENT (S (NP-SBJ (NP (DT:[994..997] The) (NN:[998..1008] inhibition)) (VP (VBN:[1009..1014] shown) (NP (-NONE-:[1014..1014] *)) (PP (IN:[1015..1017] by) (NP-LGS (NN:[1018..1028] cypro-CDCA) (CC:[1029..1032] and) (NN:[1034..1044] cypro-UDCA))))) (VP (VBD:[1045..1048] was) (ADJP-PRD (ADJP (JJR:[1049..1057] stronger)) (PP (IN:[1058..1062] than) (NP (NP (DT:[1063..1067] that)) (VP (VBN:[1068..1076] observed) (NP (-NONE-:[1076..1076] *)) (PP (IN:[1077..1081] with) (NP (DT:[1082..1085] the) (JJ:[1086..1099] corresponding) (JJ:[1100..1107] natural) (NNS:[1109..1118] compounds)))))))) (.:[1118..1119] .))) ;sentence 9 Span:1120..1237 ;22S,23S cypro-UDCA exhibited an inhibitory effect which was more pronounced ;than that of the diasteroisomer mixture. ;[1120..1138]:substance:"22S,23S cypro-UDCA" ;[1214..1236]:substance:"diasteroisomer mixture" (SENT (S (NP-SBJ (NN:[1120..1123] 22S) (,:[1123..1124] ,) (NN:[1124..1127] 23S) (NN:[1128..1138] cypro-UDCA)) (VP (VBD:[1139..1148] exhibited) (NP (NP (DT:[1149..1151] an) (JJ:[1152..1162] inhibitory) (NN:[1163..1169] effect)) (SBAR (WHNP-1 (WDT:[1170..1175] which)) (S (NP-SBJ-1 (-NONE-:[1175..1175] *T*)) (VP (VBD:[1176..1179] was) (ADJP-PRD (ADJP (RBR:[1180..1184] more) (JJ:[1186..1196] pronounced)) (PP (IN:[1197..1201] than) (NP (NP (DT:[1202..1206] that)) (PP (IN:[1207..1209] of) (NP (DT:[1210..1213] the) (NN:[1214..1228] diasteroisomer) (NN:[1229..1236] mixture))))))))))) (.:[1236..1237] .))) ;sentence 10 Span:1238..1372 ;The isomer 22R,23S was less effective and decreased cholesterol 7 ;alpha-hydroxylase activity in a manner comparable to that of UDCA. ;[1242..1256]:substance:"isomer 22R,23S" ;[1291..1322]:cyp450:"cholesterol 7 alpha-hydroxylase" ;[1367..1371]:substance:"UDCA" (SENT (S (NP-SBJ (NP (DT:[1238..1241] The) (NN:[1242..1248] isomer)) (NP (NN:[1249..1252] 22R) (,:[1252..1253] ,) (NN:[1253..1256] 23S))) (VP (VP (VBD:[1257..1260] was) (ADJP-PRD (RBR:[1261..1265] less) (JJ:[1267..1276] effective))) (CC:[1277..1280] and) (VP (VBD:[1281..1290] decreased) (NP (NML (NN:[1291..1302] cholesterol) (CD:[1303..1304] 7) (NN:[1305..1322] alpha-hydroxylase)) (NN:[1323..1331] activity)) (PP-MNR (IN:[1332..1334] in) (NP (NP (DT:[1335..1336] a) (NN:[1337..1343] manner)) (ADJP (JJ:[1345..1355] comparable) (PP (TO:[1356..1358] to) (NP (NP (DT:[1359..1363] that)) (PP (IN:[1364..1366] of) (NP (NN:[1367..1371] UDCA)))))))))) (.:[1371..1372] .))) ;sentence 11 Span:1373..1538 ;The effect of CDCA, UDCA and the cyclopropyl analogues was also tested with ;respect to HMG-CoA reductase and acylCoA cholesterol acyltransferase (ACAT) ;activities. ;[1387..1391]:substance:"CDCA" ;[1393..1397]:substance:"UDCA" ;[1406..1428]:substance:"cyclopropyl analogues" ;[1461..1478]:substance:"HMG-CoA reductase" ;[1483..1519]:substance:"acylCoA cholesterol acyltransferase" ;[1521..1525]:substance:"ACAT" (SENT (S (NP-SBJ-2 (NP (DT:[1373..1376] The) (NN:[1377..1383] effect)) (PP (IN:[1384..1386] of) (NP (NP (NN:[1387..1391] CDCA)) (,:[1391..1392] ,) (NP (NN:[1393..1397] UDCA)) (CC:[1398..1401] and) (NP (DT:[1402..1405] the) (NN:[1406..1417] cyclopropyl) (NNS:[1419..1428] analogues))))) (VP (VBD:[1429..1432] was) (ADVP (RB:[1433..1437] also)) (VP (VBN:[1438..1444] tested) (NP-2 (-NONE-:[1444..1444] *)) (PP (IN:[1445..1449] with) (NP (NP (NN:[1450..1457] respect)) (PP (TO:[1458..1460] to) (NP (NP (NML (NML (NN:[1461..1464] HMG) (HYPH:[1464..1465] -) (NN:[1465..1468] CoA)) (NN:[1469..1478] reductase)) (NML-1 (-NONE-:[1478..1478] *P*))) (CC:[1479..1482] and) (NP (NML (NML (NN:[1483..1490] acylCoA) (NN:[1492..1503] cholesterol) (NN:[1504..1519] acyltransferase)) (NML (-LRB-:[1520..1521] -LRB-) (NN:[1521..1525] ACAT) (-RRB-:[1525..1526] -RRB-))) (NML-1 (NNS:[1527..1537] activities))))))))) (.:[1537..1538] .))) ;sentence 12 Span:1539..1634 ;ACAT was stimulated by the isomer 22S,23S cypro-UDCA but not affected by the ;other bile acids. ;[1539..1543]:substance:"ACAT" ;[1566..1572]:substance:"isomer" ;[1574..1592]:substance:"22S,23S cypro-UDCA" ;[1623..1633]:substance:"bile acids" (SENT (S (NP-SBJ-1 (NN:[1539..1543] ACAT)) (VP (VBD:[1544..1547] was) (VP (VP (VBN:[1548..1558] stimulated) (NP-1 (-NONE-:[1558..1558] *)) (PP (IN:[1559..1561] by) (NP-LGS (NP (DT:[1562..1565] the) (NN:[1566..1572] isomer)) (NP (NN:[1574..1581] 22S,23S) (NN:[1582..1592] cypro-UDCA))))) (CONJP (CC:[1593..1596] but) (RB:[1597..1600] not)) (VP (VBN:[1601..1609] affected) (NP-1 (-NONE-:[1609..1609] *)) (PP (IN:[1610..1612] by) (NP-LGS (DT:[1613..1616] the) (JJ:[1617..1622] other) (NN:[1623..1627] bile) (NNS:[1628..1633] acids)))))) (.:[1633..1634] .))) ;sentence 13 Span:1635..1688 ;No effect was observed as regards HMG-CoA reductase. ;[1670..1687]:substance:"HMG-CoA reductase" (SENT (S (NP-SBJ-1 (DT:[1635..1637] No) (NN:[1638..1644] effect)) (VP (VBD:[1645..1648] was) (VP (VBN:[1650..1658] observed) (NP-1 (-NONE-:[1658..1658] *)) (PP (IN:[1659..1661] as) (S-NOM (NP-SBJ-1 (-NONE-:[1661..1661] *)) (VP (VBZ:[1662..1669] regards) (NP (NML (NN:[1670..1673] HMG) (HYPH:[1673..1674] -) (NN:[1674..1677] CoA)) (NN:[1678..1687] reductase))))))) (.:[1687..1688] .))) ;section 14 Span:1692..1736 ;PMID: 2590949 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1692..1696] PMID) (::[1696..1697] :) (CD:[1698..1705] 2590949) (-LRB-:[1706..1707] -LSB-) (NNP:[1707..1713] PubMed) (HYPH:[1714..1715] -) (NN:[1716..1723] indexed) (IN:[1724..1727] for) (NNP:[1728..1735] MEDLINE) (-RRB-:[1735..1736] -RSB-)))