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841.
JM Machinist MD Mayer EM Roberts BW Surber AD Rodrigues 《Canadian Metallurgical Quarterly》1998,26(10):970-976
In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP) forms involved in the oxidative metabolism of [14C]ABT-761 and its N-dehydroxylated metabolite, [14C]ABT-438, by human liver microsomes. The two compounds were metabolized by parallel pathways, to form the corresponding methylene bridge hydroxy metabolites. There was no evidence of sulfoxidation and/or ring hydroxylation. Over the ABT-761 and ABT-438 concentration ranges studied (1-300 microM), the rate of NADPH-dependent hydroxylation was linear with respect to substrate concentration ([S]) and did not conform to saturable Michaelis-Menten kinetics. Under these conditions ([S] < KM), the intrinsic clearance (Vmax/KM) of ABT-438 was 10-fold higher than that of ABT-761 (1.7 +/- 0.8 vs. 0.17 +/- 0.06 microl/min/mg, mean +/- SD, N = 3 livers). The hydroxylation of both compounds was shown to be highly correlated (r = 0.83, p < 0.01, N = 11 different human livers) with CYP3A-selective erythromycin N-demethylase activity, and the correlation between ABT-761 hydroxylation and tolbutamide hydroxylase (CYP2C9-selective) activity (r = 0.63, p < 0.05, N = 10) was also statistically significant. Ketoconazole (2.0 microM), a CYP3A-selective inhibitor, inhibited the hydroxylation of both compounds by 53-67%, and sulfaphenazole (CYP2C9-selective) decreased activity by 10-20%. By comparison, alpha-naphthoflavone, a known activator of CYP3A, stimulated the hydroxylation of ABT-761 (8-fold) and ABT-438 (4-fold). In addition, the abundance-normalized rates of cDNA-expressed CYP-dependent metabolism indicated that hydroxylation was largely mediated (66-86%) by CYP3A(4). Therefore, it is concluded that the hydroxylation of ABT-761 and ABT-438 (=10 microM) is primarily mediated by CYP3A, although CYP2C9 may play an ancillary role. 相似文献
842.
DG Haxby GS Rodriguez AD Zechnich RA Schuff JS Tanigawa 《Canadian Metallurgical Quarterly》1995,52(5):496-499
The distribution of drug product samples by pharmaceutical companies to a family medicine clinic was studied. Data on all deliveries of drug samples to the clinic site of a university-affiliated family medicine residency program from November 1992 through December 1993 were collected. In addition, the 11 faculty family physicians were surveyed about their experiences with the deliveries of samples. Forty-three manufacturers delivered samples of 331 drugs during the 14-month study period. There were 366 visits by the drug company representatives, who made 1117 separate deliveries. The total value of the samples, based on the average whole-sale price, was $240,782. Twenty-nine percent of the drugs were nonformulary, and only 49% were stocked by the pharmacy. The physicians surveyed indicated that they were either usually or always asked to sign for samples they did not in fact request, that they usually did not know what was recorded on the receipts for samples that they signed, and that they seldom verified what was actually delivered. Pharmaceutical manufactures delivered large quantities of drug samples during the study period, and many of the drugs were nonformulary or not stocked by the pharmacy. The physicians indicated that they were not well informed about delivered samples for which they signed receipts. 相似文献
843.
FA Raila J Zimmerman P Azordegan J Fratkin AD Parent 《Canadian Metallurgical Quarterly》1997,7(1):48-50
Image space reconstruction algorithm (ISRA) is a new kind of method for ECT reconstruction. Unlike the ML-EM algorithm which maximizes likelihood function of Possion distribution, ISRA searches for the minimum non-negative mean square solution. In this paper, an improved ISRA (IISRA) algorithm is proposed. A comparison between the algorithms (ISRA and IISRA) demonstrates that the result of IISRA is closer to the test image than that of ISRA. In addition, the IIRSA inherits some properties of ISRA such as convergence. 相似文献
844.
Effects of adrenaline and noradrenaline upon the smooth muscle contractile activity were shown to have a biphasic character. In low concentrations the effects coincide with that of phenylephrine, in high concentrations--with that of isadrine. The alpha-adrenoreceptors seem to be located at the metasympathetic neurons of the intramural ganglia and at postganglionic cholinergic nervous fibers, whereas the beta-adrenoreceptors at the smooth muscle cells. 相似文献
845.
We have determined the nucleotide sequence for the Rubisco large subunit from four holoparasitic species of Orobanche. Intact open reading frames are present in two species (O. corymbosa and O. fasciculata), whereas the remaining species (O. cernua and O. ramosa) have rbcL pseudogenes. Sequences for rbcL 5'-UTRs from species of Orobanche have few changes in the promoter and ribosome binding sites compared to photosynthetic higher plants. Comparison of rbcL 3'-UTR sequences for Nicotiana, Ipomoea, Cuscuta, and Orobanche reveal that nucleotide sequences from parasitic plants have regions capable of forming stem-loop structures, but 56-69 nt are deleted upstream of the stem-loop in the parasitic plants compared to their photosynthetic relatives. Although rbcL pseudogenes of O. cernua and O. ramosa have many large and small deletions, few indels are shared in common, implying that their common ancestor probably had an intact rbcL reading frame. Intact rbcL reading frames in O. corymbosa and O. fasciculata retain a bias of synonymous over nonsynonymous substitutions and deduced protein sequences are consistent with potentially functional Rubisco large subunit proteins. A conservative model of random substitution processes in pseudogene sequences estimates that the probability is low (P < 0.028) that these sequences would retain an open reading frame by chance. Species of Orobanche have either had recent photosynthetic ancestors, implying multiple independent losses of photosynthesis in this genus, or the rbcL gene may serve an unknown function in some nonphotosynthetic plants. 相似文献
846.
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848.
849.
Altered coronary perfusion can change the apparent diastolic stiffness of ventricular myocardium--the 'garden hose' effect. Our recent findings showed that myocardial strains are reduced during ventricular filling, primarily along the directions transverse to the coronary microvessels. In this article, we review hypotheses and theoretical models regarding the role that regional wall stress plays in the mechanical interaction between myocardium and coronary circulation. Various mechanisms have been used to explain the effects of the tissue stress on coronary flow, as well as the effect of coronary dynamics on myocardial mechanics. Many models of coronary pressure-flow relations using lumped parameter circuit analogs. Poroelasticity and swelling theories have been used to model the mechanics of perfused muscle. Here, we describe a new mathematical model of the mechanics of perfused myocardium derived using homogenization theory. In this model, perfused myocardium is treated as a nonlinear anisotropic elastic solid embedded with cylindrical vessels of known distensibility. The solid compartment is incompressible but the vascular compartment may change volume according to a simple relation between vessel diameter and perfusion pressure. The work done by the perfusion pressure in changing vascular volume contributes to the macroscopic strain energy and hence affects the stress and stiffness of the composite. Conversely, the stress in the tissue affects microvessel diameter and volume, since tractions transverse to the vessel axis oppose the internal blood pressure. Finite element simulations of passive filling show good agreement of model with experimental results. 相似文献
850.
NM Hamilton I Frade KP Duguid J Furnace AD Kindley 《Canadian Metallurgical Quarterly》1995,18(2):59-63
Digital moving images (AVI format), were integrated into a specific computer-assisted learning (CAL) application, providing a highly visual and interactive self-learning tool in an area of the medical curriculum which is difficult to teach by traditional methods. This paper outlines the process used to obtain the digital video using relatively inexpensive equipment and the subsequent delivery over a university network without resorting to major upgrading of the network specifications. 相似文献