0 7 Effects Effect NNPS 8 10 of of IN 11 21 intranasal intranasal JJ 22 37 glucocorticoids glucocorticoid NNS 38 40 on on IN 41 51 endogenous endogenous JJ 52 66 glucocorticoid glucocorticoid NN 67 77 peripheral peripheral JJ 78 81 and and CC 82 89 central central JJ 90 98 function function NN 98 99 . . . 101 116 Glucocorticoids glucocorticoid NNS 117 120 are be VBP 121 126 among among IN 127 130 the the DT 131 135 most most RBS 136 142 potent potent JJ 143 159 antiinflammatory antiinflammatory JJ 160 166 agents agent NNS 167 171 that that WDT 172 175 can can MD 176 178 be be VB 179 183 used use VBN 184 186 in in IN 187 190 the the DT 191 200 treatment treatment NN 201 203 of of IN 204 212 rhinitis rhinitis NN 212 213 . . . 214 219 Their their PRP$ 220 230 mechanisms mechanism NNS 231 233 of of IN 234 240 action action NN 241 244 are be VBP 245 253 multiple multiple JJ 254 257 and and CC 258 265 complex complex JJ 266 269 and and CC 270 271 a a DT 272 278 number number NN 279 281 of of IN 282 289 reports report NNS 290 298 describe describe VBP 299 310 significant significant JJ 311 319 systemic systemic JJ 320 327 effects effect NNS 328 330 of of IN 331 338 locally locally RB 339 351 administered administer VBN 352 367 glucocorticoids glucocorticoid NNS 367 368 . . . 369 371 In in IN 372 377 order order NN 378 380 to to TO 381 389 evaluate evaluate VB 390 393 the the DT 394 404 short-term short-term JJ 405 413 systemic systemic JJ 414 421 effects effect NNS 422 424 of of IN 425 437 intranasally intranasally RB 438 450 administered administer VBN 451 466 glucocorticoids glucocorticoid NNS 466 467 , , , 468 470 14 14 CD 471 477 normal normal JJ 478 485 healthy healthy JJ 486 494 subjects subject NNS 495 499 were be VBD 500 507 treated treat VBN 508 512 with with IN 513 516 two two CD 517 522 doses dose NNS 523 525 of of IN 526 532 either either CC 533 543 budesonide budesonide NN 544 545 ( ( ( 545 548 BUD BUD NNP 548 549 ) ) ) 550 552 or or CC 553 564 fluticasone fluticasone NN 565 575 propionate propionate NN 576 577 ( ( ( 577 579 FP FP NNP 579 580 ) ) ) 581 584 for for IN 585 586 2 2 CD 587 592 weeks week NNS 592 593 . . . 594 600 Before before IN 601 610 treatment treatment NN 610 611 , , , 612 614 at at IN 615 622 regular regular JJ 623 632 intervals interval NNS 633 639 during during IN 640 643 the the DT 644 653 treatment treatment NN 653 654 , , , 655 656 1 1 CD 657 661 week week NN 662 665 and and CC 666 673 finally finally RB 674 675 6 6 CD 676 681 weeks week NNS 682 687 after after IN 688 699 termination termination NN 700 702 of of IN 703 712 treatment treatment NN 712 713 , , , 714 717 the the DT 718 725 effects effect NNS 726 728 on on IN 729 743 glucocorticoid glucocorticoid NN 744 752 receptor receptor NN 753 754 ( ( ( 754 756 GR GR NNP 756 757 ) ) ) 758 761 and and CC 762 778 methallothionein methallothionein NN 779 780 ( ( ( 780 785 MTIIa MTIIa NNP 785 786 ) ) ) 787 791 mRNA mrna NN 792 802 expression expression NN 803 809 levels level NNS 810 814 were be VBD 815 823 examined examine VBN 824 826 in in IN 827 837 peripheral peripheral JJ 838 849 lymphocytes lymphocyte NNS 850 855 using use VBG 856 857 a a DT 858 866 solution solution NN 867 880 hybridization hybridization NN 881 886 assay assay NN 886 887 . . . 888 893 Serum Serum NNP 894 902 cortisol cortisol NN 902 903 , , , 904 915 osteocalcin osteocalcin NN 916 919 and and CC 920 927 urinary urinary JJ 928 936 cortisol cortisol NN 937 943 levels level NNS 944 948 were be VBD 949 953 also also RB 954 964 determined determine VBN 964 965 . . . 966 968 An an DT 969 976 insulin insulin NN 977 986 tolerance tolerance NN 987 991 test test NN 992 993 ( ( ( 993 996 ITT ITT NNP 996 997 ) ) ) 998 1001 was be VBD 1002 1011 performed perform VBN 1012 1014 at at IN 1015 1018 the the DT 1019 1022 end end NN 1023 1025 of of IN 1026 1029 the the DT 1030 1036 second second JJ 1037 1041 week week NN 1042 1044 of of IN 1045 1054 treatment treatment NN 1055 1058 and and CC 1059 1061 at at IN 1062 1065 the the DT 1066 1069 end end NN 1070 1072 of of IN 1073 1076 the the DT 1077 1083 6-week 6-week JJ 1084 1091 washout washout NN 1092 1098 period period NN 1099 1103 with with IN 1104 1106 no no DT 1107 1120 statistically statistically RB 1121 1132 significant significant JJ 1133 1139 change change NN 1140 1142 in in IN 1143 1151 cortisol cortisol NN 1152 1160 response response NN 1160 1161 . . . 1162 1164 In in IN 1165 1175 peripheral peripheral JJ 1176 1187 lymphocytes lymphocyte NNS 1187 1188 , , , 1189 1191 GR GR NNP 1192 1196 mRNA mRNA NNP 1197 1203 levels level NNS 1204 1208 were be VBD 1209 1222 significantly significantly RB 1223 1237 down-regulated down-regulate VBN 1237 1238 . . . 1239 1244 MTIIa MTIIa NNP 1245 1249 mRNA mRNA NNP 1250 1256 levels level NNS 1257 1266 increased increase VBD 1267 1280 significantly significantly RB 1280 1281 . . . 1282 1287 Serum Serum NNP 1288 1299 osteocalcin osteocalcin NN 1300 1309 decreased decrease VBD 1310 1323 significantly significantly RB 1324 1330 during during IN 1331 1340 treatment treatment NN 1341 1345 with with IN 1346 1350 both both CC 1351 1354 BUD BUD NNP 1355 1358 and and CC 1359 1361 FP FP NNP 1361 1362 . . . 1363 1368 Serum Serum NNP 1369 1377 cortisol cortisol NN 1378 1387 decreased decrease VBD 1388 1393 after after IN 1394 1395 1 1 CD 1396 1400 week week NN 1401 1403 of of IN 1404 1413 treatment treatment NN 1414 1421 whereas whereas IN 1422 1429 urinary urinary JJ 1430 1438 cortisol cortisol NN 1439 1442 was be VBD 1443 1446 not not RB 1447 1455 affected affect VBN 1456 1461 until until IN 1462 1465 the the DT 1466 1472 second second JJ 1473 1477 week week NN 1478 1480 of of IN 1481 1490 treatment treatment NN 1490 1491 . . . 1492 1494 In in IN 1495 1505 conclusion conclusion NN 1505 1506 , , , 1507 1517 intranasal intranasal JJ 1518 1533 glucocorticoids glucocorticoid NNS 1534 1536 at at IN 1537 1547 clinically clinically RB 1548 1559 recommended recommend VBN 1560 1565 doses dose NNS 1566 1570 have have VBP 1571 1574 not not RB 1575 1579 only only RB 1580 1591 significant significant JJ 1592 1600 systemic systemic JJ 1601 1608 effects effect NNS 1609 1611 on on IN 1612 1619 adrenal adrenal JJ 1620 1628 function function NN 1628 1629 , , , 1630 1633 but but CC 1634 1638 also also RB 1639 1643 have have VBP 1644 1646 an an DT 1647 1653 effect effect NN 1654 1656 on on IN 1657 1665 specific specific JJ 1666 1670 gene gene NN 1671 1681 expression expression NN 1682 1684 in in IN 1685 1695 peripheral peripheral JJ 1696 1707 lymphocytes lymphocyte NNS 1707 1708 . . . 1709 1714 These these DT 1715 1722 effects effect NNS 1723 1726 are be VBP 1727 1745 receptor-dependent receptor-dependent JJ 1745 1746 , , , 1747 1757 reversible reversible JJ 1757 1758 , , , 1759 1762 and and CC 1763 1772 according accord VBG 1773 1775 to to TO 1776 1781 serum serum NN 1782 1785 and and CC 1786 1793 urinary urinary JJ 1794 1802 cortisol cortisol NN 1803 1809 levels level NNS 1810 1813 and and CC 1814 1817 ITT ITT NNP 1817 1818 , , , 1819 1824 leave leave VBP 1825 1828 the the DT 1829 1859 hypothalamic-pituitary-adrenal hypothalamic-pituitary-adrenal JJ 1860 1868 function function NN 1869 1875 intact intact JJ 1875 1876 . . . 1877 1884 Finally finally RB 1884 1885 , , , 1886 1891 these these DT 1892 1902 short-term short-term JJ 1903 1911 systemic systemic JJ 1912 1919 effects effect NNS 1920 1924 were be VBD 1925 1928 not not RB 1929 1939 associated associate VBN 1940 1944 with with IN 1945 1948 any any DT 1949 1951 of of IN 1952 1955 the the DT 1956 1966 noticeable noticeable JJ 1967 1979 side-effects side-effect NNS 1980 1987 usually usually RB 1988 1996 observed observe VBN 1997 2003 during during IN 2004 2013 long-term long-term JJ 2014 2023 treatment treatment NN 2024 2028 with with IN 2029 2044 glucocorticoids glucocorticoid NNS 2044 2045 . . .