;PMID: 2779009 ;source_file_1889.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..39] = [t:0..39] ;1)sentence:[e:45..188] = [t:45..188] ;2)section:[e:192..274] = [t:192..274] ;3)section:[e:278..370] = [t:278..370] ;4)sentence:[e:374..551] = [t:374..551] ;5)sentence:[e:552..890] = [t:552..890] ;6)sentence:[e:891..988] = [t:891..988] ;7)sentence:[e:989..1085] = [t:989..1085] ;8)sentence:[e:1086..1402] = [t:1086..1402] ;9)sentence:[e:1403..1577] = [t:1403..1577] ;10)sentence:[e:1578..1755] = [t:1578..1755] ;11)section:[e:1759..1803] = [t:1759..1803] ;section 0 Span:0..39 ;Jpn J Pharmacol. 1989 Aug;50(4):435-43. (SEC (FRAG (NNP:[0..3] Jpn) (NNP:[4..5] J) (NNP:[6..15] Pharmacol) (.:[15..16] .) (CD:[17..21] 1989) (.:[22..29] Aug;50-LRB-) (CD:[29..30] 4) (-RRB-:[30..31] -RRB-) (CD:[31..38] :435-43) (.:[38..39] .))) ;sentence 1 Span:45..188 ;Species and sex differences in the inhibitory action of the corticosteroid ;alclometasone dipropionate on the hepatic drug-metabolizing system. ;[105..119]:substance:"corticosteroid" ;[121..147]:substance:"alclometasone dipropionate" ;[163..167]:substance:"drug" (SENT (NP-HLN (NP (NP (NN:[45..52] Species) (NML-1 (-NONE-:[52..52] *P*))) (CC:[53..56] and) (NP (NN:[57..60] sex) (NML-1 (NNS:[61..72] differences)))) (PP (IN:[73..75] in) (NP (NP (DT:[76..79] the) (JJ:[80..90] inhibitory) (NN:[91..97] action)) (PP (IN:[98..100] of) (NP (NP (DT:[101..104] the) (NN:[105..119] corticosteroid)) (NP (NN:[121..134] alclometasone) (NN:[135..147] dipropionate)))) (PP (IN:[148..150] on) (NP (DT:[151..154] the) (JJ:[155..162] hepatic) (ADJP (NN:[163..167] drug) (HYPH:[167..168] -) (VBG:[168..180] metabolizing)) (NN:[181..187] system))))) (.:[187..188] .))) ;section 2 Span:192..274 ;Nishibe Y, Hamataka M, Hasegawa T, Ikeuchi J, Yoshizaki T, Touchi A, ;Matsubara T. (SEC (FRAG (NNP:[192..199] Nishibe) (NNP:[200..201] Y) (,:[201..202] ,) (NNP:[203..211] Hamataka) (NNP:[212..214] M,) (NNP:[215..223] Hasegawa) (NNP:[224..225] T) (,:[225..226] ,) (NNP:[227..234] Ikeuchi) (NNP:[235..237] J,) (NNP:[238..247] Yoshizaki) (NNP:[248..249] T) (,:[249..250] ,) (NNP:[251..257] Touchi) (NNP:[258..259] A) (,:[259..260] ,) (NNP:[261..270] Matsubara) (NNP:[272..274] T.))) ;section 3 Span:278..370 ;Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., Ltd., ; Osaka, Japan. (SEC (FRAG (NNP:[278..289] Kanzakigawa) (NNP:[290..300] Laboratory) (,:[300..301] ,) (NNP:[302..310] Shionogi) (NNP:[311..319] Research) (NNP:[320..332] Laboratories) (,:[332..333] ,) (NNP:[334..342] Shionogi) (CC:[343..344] &) (NNP:[345..348] Co.) (,:[348..349] ,) (NNP:[350..354] Ltd.) (,:[354..355] ,) (NNP:[357..362] Osaka) (,:[362..363] ,) (NNP:[364..369] Japan) (.:[369..370] .))) ;sentence 4 Span:374..551 ;The effect of successive administration of the corticosteroid alclometasone ;dipropionate (ACM) on the hepatic drug-metabolizing system was examined using ; male and female rats. ;[421..435]:substance:"corticosteroid" ;[436..463]:substance:"alclometasone dipropionate" ;[465..468]:substance:"ACM" ;[485..489]:substance:"drug" (SENT (S (NP-SBJ-2 (NP (DT:[374..377] The) (NN:[378..384] effect)) (PP (IN:[385..387] of) (NP (NP (JJ:[388..398] successive) (NN:[399..413] administration)) (PP (IN:[414..416] of) (NP (NP (DT:[417..420] the) (NN:[421..435] corticosteroid)) (NP (NP (NN:[436..449] alclometasone) (NN:[451..463] dipropionate)) (NP (-LRB-:[464..465] -LRB-) (NN:[465..468] ACM) (-RRB-:[468..469] -RRB-))))))) (PP (IN:[470..472] on) (NP (DT:[473..476] the) (JJ:[477..484] hepatic) (ADJP (NN:[485..489] drug) (HYPH:[489..490] -) (VBG:[490..502] metabolizing)) (NN:[503..509] system)))) (VP (VBD:[510..513] was) (VP (VBN:[514..522] examined) (NP-2 (-NONE-:[522..522] *)) (S-MNR (NP-SBJ (-NONE-:[522..522] *)) (VP (VBG:[523..528] using) (NP (NP (JJ:[530..534] male) (NML-1 (-NONE-:[534..534] *P*))) (CC:[535..538] and) (NP (JJ:[539..545] female) (NML-1 (NNS:[546..550] rats)))))))) (.:[550..551] .))) ;sentence 5 Span:552..890 ;Although some pharmacological changes such as increases in plasma enzyme ;activity, lipid level and protein concentration appeared similarly in ;ACM-treated male and female rats, the activities of 7-alkoxycoumarin ;O-dealkylase, especially the O-depropylation activity, decreased ;dose-dependently by ACM administration only in male rats. ;[619..625]:substance:"enzyme" ;[636..641]:substance:"lipid" ;[652..659]:substance:"protein" ;[697..700]:substance:"ACM" ;[749..779]:substance:"7-alkoxycoumarin O-dealkylase" ;[853..856]:substance:"ACM" (SENT (S (SBAR-ADV (IN:[552..560] Although) (S (NP-SBJ (NP (DT:[561..565] some) (JJ:[566..581] pharmacological) (NNS:[582..589] changes)) (PP (JJ:[590..594] such) (IN:[595..597] as) (NP (NP (NNS:[598..607] increases)) (PP (IN:[608..610] in) (NP (NP (NN:[612..618] plasma) (NN:[619..625] enzyme) (NN:[626..634] activity)) (,:[634..635] ,) (NP (NN:[636..641] lipid) (NN:[642..647] level)) (CC:[648..651] and) (NP (NN:[652..659] protein) (NN:[660..673] concentration))))))) (VP (VBD:[674..682] appeared) (ADVP (RB:[683..692] similarly)) (PP-LOC (IN:[694..696] in) (NP (NP (ADJP-1 (NN:[697..700] ACM) (HYPH:[700..701] -) (VBN:[701..708] treated)) (JJ:[709..713] male) (NML-2 (-NONE-:[713..713] *P*))) (CC:[714..717] and) (NP (ADJP-1 (-NONE-:[717..717] *P*)) (JJ:[718..724] female) (NML-2 (NNS:[725..729] rats)))))))) (,:[729..730] ,) (NP-SBJ (NP (NP (DT:[731..734] the) (NNS:[735..745] activities)) (PP (IN:[746..748] of) (NP (NN:[749..765] 7-alkoxycoumarin) (NN:[767..779] O-dealkylase)))) (,:[779..780] ,) (NP (ADVP (RB:[781..791] especially)) (DT:[792..795] the) (NN:[796..811] O-depropylation) (NN:[812..820] activity))) (,:[820..821] ,) (VP (VBD:[822..831] decreased) (ADVP (NN:[833..837] dose) (HYPH:[837..838] -) (RB:[838..849] dependently)) (PP (IN:[850..852] by) (NP (NN:[853..856] ACM) (NN:[857..871] administration))) (PP-LOC (RB:[872..876] only) (IN:[877..879] in) (NP (JJ:[880..884] male) (NNS:[885..889] rats)))) (.:[889..890] .))) ;sentence 6 Span:891..988 ;ACM did not affect the hepatic drug-metabolizing activity in female rats and ;mice of both sexes. ;[891..894]:substance:"ACM" ;[923..927]:substance:"drug" (SENT (S (NP-SBJ (NN:[891..894] ACM)) (VP (VBD:[895..898] did) (RB:[899..902] not) (VP (VB:[903..909] affect) (NP (DT:[910..913] the) (JJ:[915..922] hepatic) (ADJP (NN:[923..927] drug) (HYPH:[927..928] -) (VBG:[928..940] metabolizing)) (NN:[941..949] activity)) (PP-LOC (IN:[950..952] in) (NP (NP (JJ:[953..959] female) (NNS:[960..964] rats)) (CC:[965..968] and) (NP (NP (NNS:[969..973] mice)) (PP (IN:[974..976] of) (NP (DT:[977..981] both) (NNS:[982..987] sexes)))))))) (.:[987..988] .))) ;sentence 7 Span:989..1085 ;Also, ACM did not inhibit androgen-independent aniline hydroxylase activity ;even in male rats. ;[996..999]:substance:"ACM" ;[1016..1024]:substance:"androgen" ;[1037..1056]:substance:"aniline hydroxylase" (SENT (S (ADVP (RB:[989..993] Also)) (,:[993..994] ,) (NP-SBJ (NN:[996..999] ACM)) (VP (VBD:[1000..1003] did) (RB:[1004..1007] not) (VP (VB:[1008..1015] inhibit) (NP (ADJP (NN:[1016..1024] androgen) (HYPH:[1024..1025] -) (JJ:[1025..1036] independent)) (NN:[1037..1044] aniline) (NN:[1045..1056] hydroxylase) (NN:[1057..1065] activity)) (PP-LOC (RB:[1066..1070] even) (IN:[1071..1073] in) (NP (JJ:[1075..1079] male) (NNS:[1080..1084] rats))))) (.:[1084..1085] .))) ;sentence 8 Span:1086..1402 ;The time course of changes of the drug-metabolizing system in male rats ;showed a rapid decrease in cytochrome P-450 content and O-depropylation ;activity following successive treatments with ACM, but there was a slow onset ;in the decreases of the O-demethylation and O-deethylation activities of ;7-alkoxycoumarin. ;[1120..1124]:substance:"drug" ;[1186..1202]:cyp450:"cytochrome P-450" ;[1278..1281]:substance:"ACM" ;[1385..1401]:substance:"7-alkoxycoumarin" (SENT (S (S (NP-SBJ (NP (DT:[1086..1089] The) (NN:[1090..1094] time) (NN:[1095..1101] course)) (PP (IN:[1102..1104] of) (NP (NP (NNS:[1105..1112] changes)) (PP (IN:[1113..1115] of) (NP (DT:[1116..1119] the) (ADJP (NN:[1120..1124] drug) (HYPH:[1124..1125] -) (VBG:[1125..1137] metabolizing)) (NN:[1138..1144] system))))) (PP (IN:[1145..1147] in) (NP (JJ:[1148..1152] male) (NNS:[1154..1158] rats)))) (VP (VBD:[1159..1165] showed) (NP (NP (DT:[1166..1167] a) (JJ:[1168..1173] rapid) (NN:[1174..1182] decrease)) (PP (IN:[1183..1185] in) (NP (NP (NP (NML (NN:[1186..1196] cytochrome) (NN:[1197..1202] P-450)) (NN:[1203..1210] content)) (CC:[1211..1214] and) (NP (NN:[1215..1230] O-depropylation) (NN:[1232..1240] activity))) (VP (VBG:[1241..1250] following) (NP (NP (JJ:[1251..1261] successive) (NNS:[1262..1272] treatments)) (PP (IN:[1273..1277] with) (NP (NN:[1278..1281] ACM)))))))))) (,:[1281..1282] ,) (CC:[1283..1286] but) (S (NP-SBJ (EX:[1287..1292] there)) (VP (VBD:[1293..1296] was) (NP-PRD (DT:[1297..1298] a) (JJ:[1299..1303] slow) (NN:[1304..1309] onset)) (PP (IN:[1310..1312] in) (NP (NP (DT:[1314..1317] the) (NNS:[1318..1327] decreases)) (PP (IN:[1328..1330] of) (NP (NP (DT:[1331..1334] the) (NML (NML (NN:[1335..1350] O-demethylation) (NML-1 (-NONE-:[1350..1350] *P*))) (CC:[1351..1354] and) (NML (NN:[1355..1369] O-deethylation) (NML-1 (NNS:[1370..1380] activities))))) (PP (IN:[1381..1383] of) (NP (NN:[1385..1401] 7-alkoxycoumarin))))))))) (.:[1401..1402] .))) ;sentence 9 Span:1403..1577 ;When ACM was withdrawn, the O-demethylation and O-deethylation activities ;rapidly returned to their control levels, while recovery of the ;O-depropylation activity was slow. ;[1408..1411]:substance:"ACM" (SENT (S (SBAR-TMP (WHADVP-3 (WRB:[1403..1407] When)) (S (NP-SBJ-2 (NN:[1408..1411] ACM)) (VP (VBD:[1412..1415] was) (VP (VBN:[1416..1425] withdrawn) (NP-2 (-NONE-:[1425..1425] *)) (ADVP-TMP-3 (-NONE-:[1425..1425] *T*)))))) (,:[1425..1426] ,) (NP-SBJ (DT:[1427..1430] the) (NML (NML (NN:[1431..1446] O-demethylation) (NML-1 (-NONE-:[1446..1446] *P*))) (CC:[1447..1450] and) (NML (NN:[1451..1465] O-deethylation) (NML-1 (NNS:[1467..1477] activities))))) (ADVP (RB:[1478..1485] rapidly)) (VP (VBD:[1486..1494] returned) (PP (TO:[1495..1497] to) (NP (PRP$:[1498..1503] their) (NN:[1504..1511] control) (NNS:[1512..1518] levels))) (,:[1518..1519] ,) (SBAR-ADV (IN:[1520..1525] while) (S (NP-SBJ (NP (NN:[1526..1534] recovery)) (PP (IN:[1535..1537] of) (NP (DT:[1538..1541] the) (NN:[1543..1558] O-depropylation) (NN:[1559..1567] activity)))) (VP (VBD:[1568..1571] was) (ADJP-PRD (JJ:[1572..1576] slow)))))) (.:[1576..1577] .))) ;sentence 10 Span:1578..1755 ;These results suggested that ACM inhibits the hepatic drug-metabolizing ;enzyme activity associated with a specific form(s) of androgen-dependent ;cytochrome P-450 in male rats. ;[1607..1610]:substance:"ACM" ;[1633..1637]:substance:"drug" ;[1651..1657]:cyp450:"enzyme" ;[1706..1714]:substance:"androgen" ;[1725..1741]:cyp450:"cytochrome P-450" (SENT (S (NP-SBJ (DT:[1578..1583] These) (NNS:[1584..1591] results)) (VP (VBD:[1592..1601] suggested) (SBAR (IN:[1602..1606] that) (S (NP-SBJ (NN:[1607..1610] ACM)) (VP (VBZ:[1611..1619] inhibits) (NP (NP (DT:[1620..1623] the) (JJ:[1625..1632] hepatic) (ADJP (NN:[1633..1637] drug) (HYPH:[1637..1638] -) (VBG:[1638..1650] metabolizing)) (NN:[1651..1657] enzyme) (NN:[1658..1666] activity)) (VP (VBN:[1667..1677] associated) (NP (-NONE-:[1677..1677] *)) (PP-CLR (IN:[1678..1682] with) (NP (NP (DT:[1683..1684] a) (JJ:[1685..1693] specific) (NN:[1694..1701] form-LRB-s-RRB-)) (PP (IN:[1702..1704] of) (NP (ADJP (NN:[1706..1714] androgen) (HYPH:[1714..1715] -) (JJ:[1715..1724] dependent)) (NN:[1725..1735] cytochrome) (NN:[1736..1741] P-450))))))) (PP-LOC (IN:[1742..1744] in) (NP (JJ:[1745..1749] male) (NNS:[1750..1754] rats))))))) (.:[1754..1755] .))) ;section 11 Span:1759..1803 ;PMID: 2779009 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1759..1763] PMID) (::[1763..1764] :) (CD:[1765..1772] 2779009) (NN:[1773..1774] -LSB-) (NNP:[1774..1780] PubMed) (::[1781..1782] -) (NN:[1783..1790] indexed) (IN:[1791..1794] for) (NNP:[1795..1803] MEDLINE-RSB-)))