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101.
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The kinetics of substrate removal by the liver and the resulting nonlinear changes in unbound fraction along the flow path at varying input drug concentrations were examined by a model simulation study. Specifically, we varied the binding association constant, KA, and the Michaelis-Menten constants (Km and Vmax) to examine the steady state drug removal (expressed as hepatic extraction ratio E) and changes in drug binding for (i) unienzyme systems and (ii) simple, parallel metabolic pathways; zonal metabolic heterogeneity was also added as a variable. At low KA, E declined with increasing input drug concentration, due primarily to saturation of enzymes; only small differences in binding were present across the liver. At high KA, a parabolic profile for E with concentration was observed; changes in unbound fraction between the inlet and the outlet of the liver followed in parallel fashion. Protein binding was the rate-determining step at low input drug concentrations, whereas enzyme saturation was the rate-controlling factor at high input drug concentration. Heterogeneous enzymic distribution modulated changes in unbound fraction within the liver and at the outlet. Despite marked changes in unbound fraction occurring within the liver for different enzymic distributions, the overall transhepatic differences were relatively small. We then investigated the logarithmic average unbound concentration and the length averaged concentration as estimates of substrate concentration in liver in the presence of nonlinear drug binding. Fitting of simulated data, with and without assigned random error (10%), to the Michaelis-Menten equation was performed; fitting was repeated for simulated data obtained with presence of a specific inhibitor of the high-affinity, anteriorly distributed pathway. Results were similar for both concentration terms: accurate estimates were obtained for anterior, high affinity pathways; an overestimation of parameters was observed for the lower affinity posteriorly distributed pathways. Improved estimations were found for posteriorly distributed pathways upon inhibition with specific inhibitors; with added random error, however, the improvement was much decreased. We applied the method for fitting of several sets of metabolic data obtained from rat liver perfusion studies performed with salicylamide (SAM) (i) without and (ii) with the presence of 2,6-dichloro-4-nitrophenol (DCNP), a SAM sulfation inhibitor. The fitted results showed that SAM sulfation was a high-affinity high-capacity pathway; SAM glucuronidation was of lower affinity but comparable capacity as the sulfation pathway, whereas SAM hydroxylation was of lower affinity and lower capacity. 相似文献
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One month following the Great Hanshin Earthquake of January 17, 1995, we conducted a survey of 173 hospitals in Aichi Prefecture to pinpoint problems related to their actual disaster-readiness and the medical backup systems in place to deal with such disasters. This study revealed that staff at 50% of the surveyed hospitals could reach the hospital within an hour, but that communication is almost entirely dependent on phone lines, suggesting that cordless/portable/mobile phones, radio systems, Internet, communications satellites and the like should be studied in the days to come for possible use as effective communication alternatives in times of disaster. Whereas 92% of the surveyed hospitals had manuals dealing with fire outbreaks, other areas were less well represented. For example, only 36.9% of surveyed hospitals had manuals for earthquakes, 31.7% had manuals for power outages and 14.2% had manuals to deal with flooding and water disasters. New manuals must be developed incorporating the key points garnered from experience (especially Hanshin) and be ready for use immediately. It is the time for each hospital to seriously rethink the measures it should take to deal with disasters. 相似文献
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国际上许多标准化组织都在对自动交换光网络的相关技术和标准规范进行研究。本文介绍了ITU-T、IETF和OIF等几个主要的标准化组织在自动交换光网络标准方面的进展情况。 相似文献
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CA Piantadosi J Zhang ED Levin RJ Folz DE Schmechel 《Canadian Metallurgical Quarterly》1997,147(1):103-114
Delayed neurological damage after CO hypoxia was studied in rats to determine whether programmed cell death (PCD), in addition to necrosis, is involved in neuronal death. In rats exposed to either air or CO (2500 ppm), microdialysis in brain cortex and hippocampus was performed to determine the extent of glutamate release and hydroxyl radical generation during the exposures. Groups of control and CO-exposed rats also were tested in a radial maze to assess the effects of the CO exposures on learning and memory. At 3, 7, and 21 days after CO exposure brains were perfusion-fixed and hematoxylin-eosin (H&E) was used to assess injury and to select regions for further examination. DNA fragmentation was sought by examining cryosections with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) reaction. We found significant increases in glutamate release and .OH generation during and immediately after CO hypoxia. CO-exposed rats showed learning and memory deficits after exposure associated with heterogeneous cell loss in cortex, globus pallidus, and cerebellum. The frontal cortex was affected most seriously; the damage was slight at Day 3, increased at Day 7, and persistent at Day 21 after CO exposure. TUNEL staining was positive at all three time points, and TUNEL-labeled cells were distributed similarly to eosinophilic cells. The number of cells stained by TUNEL was less than by H&E and amounted to 2 to 5% of all cell nuclei in regions of injury. Ultrastructural features of both neuronal necrosis and apoptosis also were observed readily by electron microscopy. These findings indicate that both necrosis and apoptosis (PCD) contribute to CO poisoning-induced brain cell death. 相似文献
110.
LDD方法在提高电路工作电压中的应用研究 总被引:1,自引:0,他引:1
研究了利用轻掺杂漏结构来制作高电源电压器件的工艺方法。分析了LDD结构参数对器件击穿特性的影响,并结合实验结果对N^-区的注入剂量,长度及引入的串联电阻进行了优化设计。 相似文献