Abstract:
BACKGROUND:The immunosuppressive activity of mycophenolate mofetil (MMF) is based on the reversible inhibition of inosine 5'-monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). It was the aim of this study to develop a nonradioactive method for specific measurement of IMPDH activity in isolated peripheral mononuclear cells (MNC). METHODS:The procedure is based on the incubation of lysed MNC with inosine 5'-monophosphate (IMP) followed by direct chromatographic determination of produced xanthosine 5'-monophosphate (XMP). IMPDH activity was measured in MNC of MMF-treated patients and nontreated volunteers. RESULTS:The within-run (n = 10) and between-run (n = 20) coefficients of variation (CV) for IMPDH activity were < 8% and < 10%, respectively. IMPDH activity in 60 healthy volunteers (19-63 yr) ranged from 4.72 to 32.92 nmol/h/mg protein (mean = 18.39 +/- 6.24). The IC(50) for in vitro inhibition of IMPDH activity was about 2 to 3 microg/L. Application of a single dose of 1 g MMF in dialysis patients resulted in a significant inhibition (by 47-95%; p < 0.05) of IMPDH activity in lysed MNC. CONCLUSIONS:The proposed assay specifically and reliably measures IMPDH activity in MNC. The procedure is applicable to evaluate pharmacodynamic activity in MMF-treated patients. The observed interindividual variability of IMPDH activity may reflect pharmacodynamic differences in MMF-treated patients.
journal_name
Clin Biochemjournal_title
Clinical biochemistryauthors
Glander P,Braun KP,Hambach P,Bauer S,Mai I,Roots I,Waiser J,Fritsche L,Neumayer HH,Budde Kdoi
10.1016/s0009-9120(01)00267-3subject
Has Abstractpub_date
2001-10-01 00:00:00pages
543-9issue
7eissn
0009-9120issn
1873-2933pii
S0009912001002673journal_volume
34pub_type
杂志文章abstract:OBJECTIVE:Neonatal abstinence syndrome (NAS) is a rising concern with unknown long-term effects. It is apparent that higher cost of care, impact on the community and reduced quality of life are associated with similar etiologies (e.g., fetal alcohol syndrome). Detection of drug exposure in utero allows for earlier inte...
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abstract::Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolys...
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journal_title:Clinical biochemistry
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更新日期:2004-08-01 00:00:00
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更新日期:2010-11-01 00:00:00
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更新日期:2010-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.clinbiochem.2006.04.020
更新日期:2006-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1981-04-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
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更新日期:1975-04-01 00:00:00
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更新日期:2021-01-09 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
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更新日期:2012-10-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
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更新日期:1975-12-01 00:00:00
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journal_title:Clinical biochemistry
pub_type: 杂志文章
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更新日期:2003-05-01 00:00:00