A rapid, simple and reliable high-performance liquid chromatography (HPLC) column-switching method with UV detection (270 nm) for the simultaneous determination of propentofylline and its metabolites in human and rat ...
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A rapid, simple and reliable high-performance liquid chromatography (HPLC) column-switching method with UV detection (270 nm) for the simultaneous determination of propentofylline and its metabolites in human and rat sera was developed. The method involves direct injection of serum onto an HPLC column, which contains a shielded hydrophobic stationary phase for the separation of analytes from proteins in serum, and then loading the analytes onto a short octadecylsilylated silica gel (ODS) column using a switching valve. Propentofylline and its three metabolites in serum were separated from the serum components within 30 min after the injection. The detection limits (S/N= 3) of analytes spiked in human and rat sera ranged from 0.08 to 0.57 nmol/mL, and the net volume of serum used was 20 mu L. The relative standard deviations for within- and between-day variations using rat serum were less than 4.3 and 5.6%, respectively. The method was used to determine propentofylline and its main metabolites in rat serum after a single intravenous dose of propentofylline (5 mg/kg). Copyright (C) 1999 John Wiley & Sons, Ltd.
A new series of imidazolyl nitrones spin traps has been synthesized and evaluated pharmacologically. The salient structural feature of these molecules is the presence of an imidazole moiety substituted by aromatic or ...
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A new series of imidazolyl nitrones spin traps has been synthesized and evaluated pharmacologically. The salient structural feature of these molecules is the presence of an imidazole moiety substituted by aromatic or heteroaromatic cycles. This connectivity imparts to the nitrone superior neuroprotective properties in vivo and in parallel reduced side effects and toxicity. Thus compound 6a (a 2-phenylimidazolyl nitrone) administered intraperitoneally protects (80%) mice from lethality induced by an intracerebroventricular administration of tert-butyl hydroperoxide (t-BHP) an oxidant capable of inducing neurodegenerative processes. Administration of the archetypal nitrone phenyl-tert-butyl nitrone (PBN) at an equimolar dose also affords some protection (60%) in this test. However, this activity is accompanied by hypothermia, whereas no such effect is apparent for 6a. Moreover, previously prepared nonsubstituted or alkyl-substituted imidazolyl nitrones were shown to be extremely toxic to rats in contrast to the compounds prepared in this study. The observed activities in vivo correlate well with the calculated partition coefficients (ClogP) and HOMO energy level.
Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-HuEPO) is directly injected into ischemic rodent brain. We observed abundant expressi...
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Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-HuEPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by approximate to 50-75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate, Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-HuEPO as a general neuroprotective treatment are warranted.
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