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R Hajdu R Thompson JG Sundelof BA Pelak FA Bouffard JF Dropinski H Kropp 《Canadian Metallurgical Quarterly》1997,41(11):2339-2344
MK-0991 (L-743,872) is a potent antifungal agent featuring long half-life pharmacokinetics. The pharmacokinetics of MK-0991 administered intravenously to mice, rats, rhesus monkeys, and chimpanzees is presented. Unique to MK-0991 is its consistent cross-species performance. The range of values for the pharmacokinetic parameters were as follows: clearance, 0.26 to 0.51 ml/min/kg; half-life, 5.2 to 7.6 h; and distributive volume, 0.11 to 0.27 liters/kg. The level of protein binding of MK-0991 was determined to be 96% in mouse and human serum. The compound exhibited high affinities for human serum albumin and at least two lipid components. The rationale for the selection of MK-0991 as a drug development candidate was based on its two- to threefold superior pharmacokinetic performance in chimpanzees over the performance of an otherwise equivalent analog, L-733,560. Once-daily dosing for MK-0991 is indicated by a graphical comparison of levels in the circulations of chimpanzees and mice. In a study of the pharmacokinetics of MK-0991 in mouse tissue, the organs were assayed following intraperitoneal administration. The area under the concentration-versus-time curves (AUC) segregated the tissues into three exposure categories relative to plasma. The tissues with greater exposure than that for plasma were liver (16 times), kidney (3 times), and large intestine (2 times). The exposure for small intestine, lung, and spleen were equivalent to that for plasma. Organs with lower levels of exposure were the heart (0.3 times that for plasma), thigh (0.2 times), and brain (0.06 times). Kinetically, drug was cleared more slowly from all tissues than from plasma, indicating that terminal-phase equilibrium had not been achieved by 24 h. Thus, some measure of accumulation is predicted for all tissues. Single daily doses of MK-0991 should provide adequate systemic levels of fungicidal activity as a result of its long half-life pharmacokinetics, wide distribution, and slowly accumulating concentrations in tissue. 相似文献
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Four ruminally and abomasally cannulated steers were used to evaluate the effects of barely variety on rate, site, and extent of digestion of high-concentrate diets. The treatments compared were 1) corn, 2) Gunhilde barley (GUN), Harrington barley (HAR), and 4) Medallion barley (MED). Diets were balanced to be isocaloric and isonitrogenous. Ruminal OM digestion was greater (P = .04) in steers fed corn than in those fed GUN, HAR, and MED (61.9 vs average 53.7%). No differences (P > .10) were seen in ruminal starch digestion (average 92.8%) or in starch flow to the abomasum (average 199 g/d) between diets. Total tract digestion of starch was greater (P = .09) in steers fed barley than in those fed corn (average 98.6 vs 95.7%). Total and nonammonia N presented to the abomasum were greater (P < .05) for steers fed HAR and GUN than for those fed MED and corn. Microbial N flow was lowest (P = .01) in corn-fed steers, highest in steers fed GUN and HAR, and intermediate in steers fed MED. Microbial efficiency was 59% greater (P = .03) in steers fed barley than in steers consuming corn. Ruminal acetate: propionate was lower (P = .002) in steers fed corn and HAR than in those fed GUN and MED. Compared to GUN, HAR, and MED barleys, corn had a lower (P < .03) rate (-.11 vs average -.47) and extent (15 h; 70.3 vs average 98.1%) of in situ starch disappearance. Differences in digestive characteristics found between barley varieties may contribute to differences in animal performance. 相似文献
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Performance and optimization of a combustion interface for isotope ratio monitoring gas chromatography/mass spectrometry 总被引:3,自引:0,他引:3
Conditions and systems for on-line combustion of effluents from capillary gas chromatographic columns and for removal of water vapor from product streams were tested. Organic carbon in gas chromatographic peaks 15 s wide and containing up to 30 nanomoles of carbon was quantitatively converted to CO2 by tubular combustion reactors, 200 x 0.5 mm, packed with CuO or NiO. No auxiliary source of O2 was required because oxygen was supplied by metal oxides. Spontaneous degradation of CuO limited the life of CuO reactors at T > 850 degrees C. Since NiO does not spontaneously degrade, its use might be favored, but Ni-bound carbon phases form and lead to inaccurate isotopic results at T < 1050 degrees C if gas-phase O2 is not added. For all compounds tested except CH4, equivalent isotopic results are provided by CuO at 850 degrees C, NiO + O2 (gas-phase mole fraction, 10(-3)) at 1050 degrees C and NiO at 1150 degrees C. The combustion interface did not contribute additional analytical uncertainty, thus observed standard deviations of 13C/12C ratios were within a factor of 2 of shot-noise limits. For combustion and isotopic analyses of CH4, in which quantitative combustion required T approximately 950 degrees C, NiO-based systems are preferred, and precision is approximately 2 times lower than that observed for other analytes. Water must be removed from the gas stream transmitted to the mass spectrometer or else protonation of CO2 will lead to inaccuracy in isotopic analyses. Although thresholds for this effect vary between mass spectrometers, differential permeation of H2O through Nafion tubing was effective in both cases tested, but the required length of the Nafion membrane was 4 times greater for the more sensitive mass spectrometer. 相似文献
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The removal of most ceramic brackets is accomplished by specially designed pliers that apply some form of tensile or shear force to the tooth surface. While the shear and tensile bond strengths for ceramic brackets in vitro have been reported, a simulation of the actual force application when using sharp-edged debonding pliers to debond a bracket has not. The purpose of this study is to determine the effectiveness and the force levels generated by the use of both the wide and the narrow blades in the debonding of ceramic brackets. The present findings indicate that the narrow blades effectively debonded ceramic brackets with a significantly lower mean debonding force (120 kg/cm2) than the wider blades (150 kg/cm2). The surface area of the blade in contact with the bracket-adhesive interface is less for the narrow blade (2.0 mm) than for the wide blade (3.2 mm). This relatively smaller contact area is sufficient to debond a bracket at a significantly lower debonding force. 相似文献
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DG Lambie JW Paxon RN Nanda RH Johnson JG Ratcliffee ID Melville GD Morrice 《Canadian Metallurgical Quarterly》1976,21(2):93-94
Using Wistar stain male rats, it has been shown that 2 atmospheric pressures associated with oxygen saturation, together or singly for 90 minutes daily for successive 46 days, resulted in no significant change on the ratio of testes to body weight. No significant change was observed in the incorporation of 3H-thymidine into testes and pituitary glands between the pressure-treated groups and the control group. 相似文献