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1.
X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C–H, C–C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C–O), carbon-yls (C = O), and carboxylic acids or esters (O–C = O). The C–O functional state contributed approximately 60–70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C–O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C–O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals.  相似文献   

2.
The human [12-Asparagine-B] insulin ([Asn12-B] insulin) which differs from the parent molecule in that the valine residue at position B12 is substituted by an asparagine residue, has been synthesized by the procedures developed in this laboratory. In stimulating glucose oxidation and lipogenesis the analogue exhibited potencies of 0.19% and 0.14%, respectively, as compared to insulin. In insulin receptor binding [Asn12-B] insulin was found to possess a potency of ca. 0.29% compared to the natural hormone. At high concentrations this analogue is shown to have the same maximal activity in the in vitro assays as the natural hormone. This indicates that despite the low affinity of the analogue for the insulin receptor, the analogue-receptor complex is fully capable of initiating the series of chemical events that leads to the biological response. It is concluded that the B12 valine contributes greatly in the maintenance of a structure possessing the proper receptor-binding characteristics, but does not have any role in modulating the activity of the hormone-receptor complex. The potency of this analogue by radioimmunoassay is at least 100-fold higher than the in vitro biological assays, indicating that the immunological determinants of insulin can be essentially unrelated to the biological activity of the molecule.  相似文献   

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Abstract

Objective:

To examine the management of basal insulin analogue initiation in combination with oral antidiabetic drug (OAD) therapy in elderly patients with type 2 diabetes (aged ≥70 years) by physicians via comparison to the same treatment strategy in younger individuals (<70 years).  相似文献   

5.
This study aimed to assess the impact of multi‐route co‐exposures to chemicals on interindividual variability in toxicokinetics. Probabilistic physiologically based pharmacokinetic multi‐route interaction models were developed for adults and four younger subpopulations. Drinking water‐mediated multi‐route exposures were simulated for benzene alone or in co‐exposure with toluene, ethylbenzene and m‐xylene, for trichloroethylene or vinyl chloride (VC), alone and in mixture. These simulations were performed for “low” and “high” exposure scenarios, involving respectively the US EPA's short‐term drinking water health advisories, and 10 times these advisory values. Distributions of relevant internal dose metrics for benzene, trichloroethylene and VC were obtained using Monte Carlo simulations. Intergroup variability indexes (VI) were computed for the “low” (VIL) and “high” (VIH) exposure scenarios, as the ratio between the 95th percentile in each subpopulation over the median in adults. Thus, for benzene, parent compound's area under the curve‐based VIL for single exposures vs. co‐exposures correspondingly varied between 1.7 (teenagers) and 2.8 (infants) vs. 1.9 and 3.1 respectively. VIH varied between 2.5 and 3.5 vs. 2.9 and 4.1. Inversely, VIL and VIH for the amount of benzene metabolized via CYP2E1 pathway decreased in co‐exposure compared to single exposure. For VC and trichloroethylene, similar results were obtained for the “high” exposure, but “low” co‐exposures did not impact the toxicokinetics of individual substances. In conclusion, multi‐route co‐exposures can have an impact on the toxicokinetics of individual substances, but to an extent, that does not seem to challenge the default values attributed to the factors deemed at reflecting interindividual or child/adult differences in toxicokinetics.  相似文献   

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