;PMID: 4052099 ;source_file_1885.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..44] = [t:0..44] ;1)sentence:[e:50..174] = [t:50..174] ;2)section:[e:178..199] = [t:178..199] ;3)sentence:[e:203..420] = [t:203..420] ;4)sentence:[e:421..555] = [t:421..555] ;5)sentence:[e:556..706] = [t:556..706] ;6)sentence:[e:707..864] = [t:707..864] ;7)sentence:[e:865..1043] = [t:865..1043] ;8)sentence:[e:1044..1125] = [t:1044..1125] ;9)sentence:[e:1126..1207] = [t:1126..1207] ;10)sentence:[e:1208..1327] = [t:1208..1327] ;11)sentence:[e:1328..1428] = [t:1328..1428] ;12)sentence:[e:1429..1602] = [t:1429..1602] ;13)section:[e:1606..1650] = [t:1606..1650] ;section 0 Span:0..44 ;Biochem Pharmacol. 1985 Oct 1;34(19):3571-5. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..17] Pharmacol) (.:[17..18] .) (CD:[19..23] 1985) (NNP:[24..27] Oct) (CC:[28..33] 1;34-LRB-) (CD:[33..35] 19) (-RRB-:[35..36] -RRB-) (::[36..37] :) (CD:[37..41] 3571) (CD:[41..43] -5) (.:[43..44] .))) ;sentence 1 Span:50..174 ;Phase 1 and Phase 2 drug metabolism in isolated epidermal cells from adult ;hairless mice and in whole human hair follicles. ;[70..74]:substance:"drug" (SENT (NP-HLN (NP (NP (NML (NN:[50..55] Phase) (CD:[56..57] 1)) (NML-1 (-NONE-:[57..57] *P*))) (CC:[58..61] and) (NP (NML (NN:[62..67] Phase) (CD:[68..69] 2)) (NML-1 (NN:[70..74] drug) (NN:[75..85] metabolism)))) (PP-LOC (PP (IN:[86..88] in) (NP (NP (VBN:[89..97] isolated) (JJ:[98..107] epidermal) (NNS:[108..113] cells)) (NP (IN:[114..118] from) (NP (JJ:[119..124] adult) (JJ:[126..134] hairless) (NNS:[135..139] mice))))) (CC:[140..143] and) (PP (IN:[144..146] in) (NP (JJ:[147..152] whole) (JJ:[153..158] human) (NN:[159..163] hair) (NNS:[164..173] follicles)))) (.:[173..174] .))) ;section 2 Span:178..199 ;Finnen MJ, Shuster S. (SEC (FRAG (NNP:[178..184] Finnen) (NNP:[185..187] MJ) (,:[187..188] ,) (NNP:[189..196] Shuster) (NNP:[197..199] S.))) ;sentence 3 Span:203..420 ;A sensitive fluorimetric assay to determine both Phase 1 (oxidation) and ;Phase 2 (conjugation) drug metabolism in epidermal cells isolated from ;hairless mice, using ethoxycoumarin as a model substrate, is described. ;[299..303]:substance:"drug" ;[370..384]:substance:"ethoxycoumarin" ;[396..405]:substance:"substrate" (SENT (S (NP-SBJ-2 (NP (DT:[203..204] A) (JJ:[205..214] sensitive) (JJ:[215..227] fluorimetric) (NN:[228..233] assay)) (SBAR (WHNP-3 (-NONE-:[233..233] 0)) (S (NP-SBJ-3 (-NONE-:[233..233] *)) (VP (TO:[234..236] to) (VP (VB:[237..246] determine) (NP (CC:[247..251] both) (NP (NML (NML (NN:[252..257] Phase) (CD:[258..259] 1)) (NML (-LRB-:[260..261] -LRB-) (NN:[261..270] oxidation) (-RRB-:[270..271] -RRB-))) (NML-1 (-NONE-:[271..271] *P*))) (CC:[272..275] and) (NP (NML (NML (NN:[276..281] Phase) (CD:[282..283] 2)) (NML (-LRB-:[285..286] -LRB-) (NN:[286..297] conjugation) (-RRB-:[297..298] -RRB-))) (NML-1 (NN:[299..303] drug) (NN:[304..314] metabolism)))) (PP-LOC (IN:[315..317] in) (NP (NP (JJ:[318..327] epidermal) (NNS:[328..333] cells)) (VP (VBN:[334..342] isolated) (NP (-NONE-:[342..342] *)) (PP (IN:[343..347] from) (NP (JJ:[348..356] hairless) (NNS:[357..361] mice)))))) (,:[361..362] ,) (S-MNR (NP-SBJ (-NONE-:[362..362] *)) (VP (VBG:[364..369] using) (NP (NN:[370..384] ethoxycoumarin)) (PP (IN:[385..387] as) (NP (DT:[388..389] a) (NN:[390..395] model) (NN:[396..405] substrate)))))))))) (,:[405..406] ,) (VP (VBZ:[407..409] is) (VP (VBN:[410..419] described) (NP-2 (-NONE-:[419..419] *)))) (.:[419..420] .))) ;sentence 4 Span:421..555 ;Ethoxycoumarin was metabolized by isolated epidermal cells via dealkylation ;to 7-hydroxycoumarin (7-OHC) and subsequent conjugation. ;[421..435]:substance:"Ethoxycoumarin" ;[501..518]:substance:"7-hydroxycoumarin" ;[521..526]:substance:"7-OHC" (SENT (S (NP-SBJ-1 (NN:[421..435] Ethoxycoumarin)) (VP (VBD:[436..439] was) (VP (VBN:[441..452] metabolized) (NP-1 (-NONE-:[452..452] *)) (PP (IN:[453..455] by) (NP-LGS (VBN:[456..464] isolated) (JJ:[465..474] epidermal) (NNS:[475..480] cells))) (PP-MNR (IN:[481..484] via) (NP (NP (NP (NN:[485..497] dealkylation)) (PP (TO:[498..500] to) (NP (NP (NN:[501..518] 7-hydroxycoumarin)) (NP (-LRB-:[520..521] -LRB-) (NN:[521..526] 7-OHC) (-RRB-:[526..527] -RRB-))))) (CC:[528..531] and) (NP (JJ:[532..542] subsequent) (NN:[543..554] conjugation)))))) (.:[554..555] .))) ;sentence 5 Span:556..706 ;Phase 1 metabolites were extracted in ether from the aqueous incubation ;media, back extracted into sodium hydroxide and determined ;fluorimetrically. ;[564..575]:substance:"metabolites" ;[594..599]:substance:"ether" ;[629..634]:substance:"media" ;[656..672]:substance:"sodium hydroxide" (SENT (S (NP-SBJ-1 (NML (NN:[556..561] Phase) (CD:[562..563] 1)) (NNS:[564..575] metabolites)) (VP (VBD:[576..580] were) (VP (VP (VBN:[581..590] extracted) (NP-1 (-NONE-:[590..590] *)) (NP (IN:[591..593] in) (NP (NN:[594..599] ether))) (PP (IN:[601..605] from) (NP (DT:[606..609] the) (JJ:[610..617] aqueous) (NN:[618..628] incubation) (NN:[629..634] media)))) (,:[634..635] ,) (VP (RB:[636..640] back) (VBN:[641..650] extracted) (NP-1 (-NONE-:[650..650] *)) (PP (IN:[651..655] into) (NP (NN:[656..662] sodium) (NN:[663..672] hydroxide)))) (CC:[673..676] and) (VP (VBN:[678..688] determined) (NP-1 (-NONE-:[688..688] *)) (ADVP-MNR (RB:[689..705] fluorimetrically))))) (.:[705..706] .))) ;sentence 6 Span:707..864 ;Conjugated metabolites remaining in the aqueous phase were hydrolysed by the ;action of beta-glucuronidase and extracted and determined in a similar ;manner. ;[718..729]:substance:"metabolites" ;[795..813]:substance:"beta-glucuronidase" (SENT (S (NP-SBJ-1 (NP (VBN:[707..717] Conjugated) (NNS:[718..729] metabolites)) (VP (VBG:[730..739] remaining) (PP (IN:[740..742] in) (NP (DT:[743..746] the) (JJ:[747..754] aqueous) (NN:[756..761] phase))))) (VP (VBD:[762..766] were) (VP (VP (VBN:[767..777] hydrolysed) (NP-1 (-NONE-:[777..777] *)) (PP-MNR (IN:[778..780] by) (NP (NP (DT:[781..784] the) (NN:[785..791] action)) (PP (IN:[792..794] of) (NP (NN:[795..813] beta-glucuronidase)))))) (CC:[814..817] and) (VP (VBN:[818..827] extracted) (CC:[828..831] and) (VBN:[833..843] determined) (NP-1 (-NONE-:[843..843] *)) (PP-MNR (IN:[844..846] in) (NP (DT:[847..848] a) (JJ:[849..856] similar) (NN:[857..863] manner)))))) (.:[863..864] .))) ;sentence 7 Span:865..1043 ;The production of free 7-OHC by isolated epidermal cells was biphasic at all ;substrate concentrations tested, exhibiting an initial linear increase ;followed by a plateau phase. ;[888..893]:substance:"7-OHC" ;[943..952]:substance:"substrate" (SENT (S (NP-SBJ (NP (DT:[865..868] The) (NN:[869..879] production)) (PP (IN:[880..882] of) (NP (JJ:[883..887] free) (NN:[888..893] 7-OHC))) (PP (IN:[894..896] by) (NP (VBN:[897..905] isolated) (JJ:[907..916] epidermal) (NNS:[917..922] cells)))) (VP (VBD:[923..926] was) (ADJP-PRD (JJ:[927..935] biphasic)) (PP (IN:[936..938] at) (NP (NP (DT:[939..942] all) (NN:[943..952] substrate) (NNS:[953..967] concentrations)) (VP (VBN:[968..974] tested) (NP (-NONE-:[974..974] *))))) (,:[974..975] ,) (S-ADV (NP-SBJ (-NONE-:[975..975] *)) (VP (VBG:[976..986] exhibiting) (NP (NP (DT:[988..990] an) (JJ:[991..998] initial) (JJ:[999..1005] linear) (NN:[1006..1014] increase)) (VP (VBN:[1015..1023] followed) (NP (-NONE-:[1023..1023] *)) (PP (IN:[1024..1026] by) (NP-LGS (DT:[1027..1028] a) (NN:[1029..1036] plateau) (NN:[1037..1042] phase)))))))) (.:[1042..1043] .))) ;sentence 8 Span:1044..1125 ;The plateau phase was attributable to the conjugation of 7-OHC produced in ;situ. ;[1102..1107]:substance:"7-OHC" (SENT (S (NP-SBJ (DT:[1044..1047] The) (NN:[1048..1055] plateau) (NN:[1056..1061] phase)) (VP (VBD:[1062..1065] was) (ADJP-PRD (JJ:[1067..1079] attributable) (PP (TO:[1080..1082] to) (NP (NP (DT:[1083..1086] the) (NN:[1087..1098] conjugation)) (PP (IN:[1099..1101] of) (NP (NP (NN:[1102..1107] 7-OHC)) (VP (VBN:[1108..1116] produced) (NP (-NONE-:[1116..1116] *)) (ADVP (FW:[1117..1119] in) (FW:[1120..1124] situ))))))))) (.:[1124..1125] .))) ;sentence 9 Span:1126..1207 ;Metabolism was inhibited by SKF 525A, carbon monoxide, and ;alpha-naphthoflavone. ;[1155..1163]:substance:"SKF 525A" ;[1165..1180]:substance:"carbon monoxide" ;[1186..1206]:substance:"alpha-naphthoflavone" (SENT (S (NP-SBJ-1 (NN:[1126..1136] Metabolism)) (VP (VBD:[1137..1140] was) (VP (VBN:[1142..1151] inhibited) (NP-1 (-NONE-:[1151..1151] *)) (PP (IN:[1152..1154] by) (NP-LGS (NP (NN:[1155..1158] SKF) (NN:[1159..1163] 525A)) (,:[1163..1164] ,) (NP (NN:[1165..1171] carbon) (NN:[1172..1180] monoxide)) (,:[1180..1181] ,) (CC:[1182..1185] and) (NP (NN:[1186..1206] alpha-naphthoflavone)))))) (.:[1206..1207] .))) ;sentence 10 Span:1208..1327 ;Endogenous supplies of reducing equivalents in the form of NADPH were ;adequate to attain maximal rates of metabolism. ;[1268..1273]:substance:"NADPH" (SENT (S (NP-SBJ (NP (JJ:[1208..1218] Endogenous) (NNS:[1220..1228] supplies)) (PP (IN:[1229..1231] of) (NP (NP (VBG:[1232..1240] reducing) (NNS:[1241..1252] equivalents)) (PP (IN:[1253..1255] in) (NP (NP (DT:[1256..1259] the) (NN:[1260..1264] form)) (PP (IN:[1265..1267] of) (NP (NN:[1268..1273] NADPH)))))))) (VP (VBD:[1274..1278] were) (ADJP-PRD (JJ:[1279..1287] adequate)) (S-PRP (NP-SBJ (-NONE-:[1287..1287] *)) (VP (TO:[1288..1290] to) (VP (VB:[1291..1297] attain) (NP (NP (JJ:[1299..1306] maximal) (NNS:[1307..1312] rates)) (PP (IN:[1313..1315] of) (NP (NN:[1316..1326] metabolism)))))))) (.:[1326..1327] .))) ;sentence 11 Span:1328..1428 ;With human hair follicles both Phase 1 and Phase 2 activity was detectable ;in 7 out of 11 subjects. (SENT (S (PP (IN:[1328..1332] With) (NP (JJ:[1333..1338] human) (NN:[1339..1343] hair) (NNS:[1344..1353] follicles))) (NP-SBJ (CC:[1354..1358] both) (NP (NML (NN:[1359..1364] Phase) (CD:[1365..1366] 1)) (NML-1 (-NONE-:[1366..1366] *P*))) (CC:[1367..1370] and) (NP (NML (NN:[1371..1376] Phase) (CD:[1377..1378] 2)) (NML-1 (NN:[1380..1388] activity)))) (VP (VBD:[1389..1392] was) (ADJP-PRD (JJ:[1393..1403] detectable)) (PP-LOC (IN:[1404..1406] in) (NP (NP (CD:[1407..1408] 7)) (PP (IN:[1409..1412] out) (PP (IN:[1413..1415] of) (NP (CD:[1416..1418] 11) (NNS:[1419..1427] subjects))))))) (.:[1427..1428] .))) ;sentence 12 Span:1429..1602 ;The assay has the advantages of being sensitive, producing single defined ;metabolites from both Phase 1 and Phase 2 metabolism; is readily adaptable ;to human skin samples. ;[1504..1515]:substance:"metabolites" (SENT (S (NP-SBJ (DT:[1429..1432] The) (NN:[1433..1438] assay)) (VP (VP (VBZ:[1439..1442] has) (NP (NP (DT:[1443..1446] the) (NNS:[1447..1457] advantages)) (PP (IN:[1458..1460] of) (S-NOM (S (NP-SBJ (-NONE-:[1460..1460] *)) (VP (VBG:[1462..1467] being) (ADJP-PRD (JJ:[1468..1477] sensitive)))) (,:[1477..1478] ,) (S (NP-SBJ (-NONE-:[1478..1478] *)) (VP (VBG:[1479..1488] producing) (NP (NP (JJ:[1489..1495] single) (VBN:[1496..1503] defined) (NNS:[1504..1515] metabolites)) (PP (IN:[1516..1520] from) (NP (CC:[1521..1525] both) (NP (NML (NN:[1526..1531] Phase) (CD:[1532..1533] 1)) (NML-1 (-NONE-:[1533..1533] *P*))) (CC:[1534..1537] and) (NP (NML (NN:[1539..1544] Phase) (CD:[1545..1546] 2)) (NML-1 (NN:[1547..1557] metabolism)))))))))))) (::[1557..1558] ;) (VP (VBZ:[1559..1561] is) (ADJP-PRD (RB:[1562..1569] readily) (JJ:[1570..1579] adaptable) (PP (TO:[1580..1582] to) (NP (JJ:[1583..1588] human) (NN:[1589..1593] skin) (NNS:[1594..1601] samples)))))) (.:[1601..1602] .))) ;section 13 Span:1606..1650 ;PMID: 4052099 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1606..1610] PMID) (::[1610..1611] :) (CD:[1612..1619] 4052099) (NN:[1620..1621] -LSB-) (NNP:[1621..1627] PubMed) (::[1628..1629] -) (NN:[1630..1637] indexed) (IN:[1638..1641] for) (NNP:[1642..1650] MEDLINE-RSB-)))