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(R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 (CYP or P450) 2A6. Menthofuran caused a time- and concentration-dependent loss of CYP2A6 activity. The inactivation of CYP2A6 was characterized by a Ki of 2.5 microM and a kinact of 0.22 min-1 for human liver microsomes and a Ki of 0.84 microM and a kinact of 0.25 min-1 for purified expressed CYP2A6. Addition of various nucleophiles, a chelator of iron, or scavengers of reactive oxygen species or extensive dialysis failed to protect CYP2A6 from inactivation. An antibody to metallothionein conjugates of a suspected reactive metabolite of menthofuran was used to detect reactive menthofuran metabolite adducts with CYP2A6. These adducts were formed only in the presence of NADPH-P450 reductase and NADPH. Glutathione, methoxylamine, and semicarbazide did not prevent adduction of reactive menthofuran metabolites to CYP2A6, however. The menthofuran metabolite formation/CYP2A6 inactivation partition ratio was determined to be 3.5 +/- 0.6 nmol/nmol of P450. Menthofuran was unable to inactivate CYP1A2, CYP2D6, CYP2E1, or CYP3A4 in a time- and concentration-dependent manner. 相似文献
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Bremsstrahlung x-rays are produced when energetic beta-particles are emitted and absorbed. Measurements of total-body bremsstrahlung efficiencey (x-ray photon output per muCi 90Sr in the body, relative to that in water) have been made in the intact mouse, rat, rabbit, and dog sacrificed 2 weeks after the injection of 90Sr + 85Sr. Efficiencies were determined by a comparison of the bremsstrahlung output from 90Sr + its daughter 90Y and the gamma-ray emission of 85Sr. Results were checked by a beta-assay of the ashed animals. Bremsstrahlung efficiencies averaged 1.10 in a 0.04 kg mouse, 1.14 in a 0.13 kg rat, 1.23 in a 2.6 kg rabbit, and 1.32 in an 8.5 kg beagle. Extrapolating to a 70 kg human, a relative bremsstrahlung efficiency of about 1.4 is predicted. An estimate was made of the 90Sr body content in a former dial painter based on in vivo counting and a bremsstrahlung efficiency of 1.39 predicted for a 55 kg human female by these animal data. Our value of 1.42 +/- 0.08 muCi 90Sr was in good agreement with corresponding results reported for this subject by 8 other laboratories. 相似文献
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The Wechsler Adult Intelligence Scale (WAIS) was administered to two groups of patients in the Santa Clara County Methadone Maintenance Program who were receiving low and moderate daily stabilized dosages of methadone hydrochloride. In the two separate statistical analyses performed, there were no significant differences found between subtest scores or verbal, performance, and full-scale scores of the groups measured. These results, combined with observations regarding the similarities of WAIS profiles of the two groups, indicate that cognitive functioning as measured by the WAIS was not differentially affected by the two dosages. 相似文献
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The present study was undertaken to evaluate if plasma or CSF beta-endorphin level can be induced to rise during the treatment of heroin addiction by electroacupuncture. Based on the examination of 30 addicts, we obtained no evidence indicating an increase of beta-endorphin level in either the plasma or the CSF after 30 min of acupuncture. In spite of this, the majority of the addicts experienced a reduction of withdrawal symptoms during treatment. Since electroacupuncture may only induce a highly localized secretion of beta-endorphin in the brain, our results cannot unequivocally exclude the possibility that this peptide is involved in mediating the action of acupuncture. 相似文献
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Poly(L-lactide)-block-poly(ethylene oxide)-block-poly(L-lactide) triblock copolymers (PLLA-b-PEO-b-PLLA) were fractionated in terms of the number of LLA units by liquid chromatography at the critical condition (LCCC) of PEO block. The fractionated samples were identified using MALDI-TOF mass spectrometry. The dependence of the LCCC retention of the diblock and triblock copolymers on the degree of polymerization of PLLA block(s) follows Martin's rule very well. Unlike the case of PEO-b-PLLA diblock copolymer reported earlier (Lee, H.; et al. Macromolecules 1999, 32, 4143), however, a splitting of the elution peaks containing the same number of LLA units was found. The peak splitting was ascribed to the different length distributions of PLLA blocks at the two ends of the PEO block. From the relative intensities of the peaks, the split peaks were assigned to different isomeric structures of the PLLA blocks. From these results we conclude that the interaction of the triblock copolymers with the stationary phase is affected by the distribution of the interacting blocks at the two ends of the center PEO block, in addition to the total number of LLA units in the triblock copolymer. 相似文献
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