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91.
The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development. 相似文献
92.
CT Lai VA Tanay GA Rauw AN Bateson IL Martin GB Baker 《Canadian Metallurgical Quarterly》1997,704(1-2):175-179
Reported here is a rapid, sensitive and relatively inexpensive procedure using gas chromatography with nitrogen-phosphorus detection (GC-NPD) to quantify buspirone levels in brains of rats. The analyte was directly extracted from brain homogenate with toluene after basification and then subjected to GC-NPD analysis using a capillary column. The calibration curves were linear over the range of 10 to 320 ng per 2 ml of brain homogenate, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties. 相似文献
93.
M Cuchacovich NN Tchernitchin H Gatica R Wurgaft L Contreras AN Tchernitchin 《Canadian Metallurgical Quarterly》1996,124(2):160-169
BACKGROUND: The target cellular response to glucocorticoids is proportional to the concentrations or affinity of specific receptors to these substances. AIM: To look for a correlation between glucocorticoid receptor concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. PATIENTS AND METHODS: Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy, in which a dry radioautographic technique for diffusible compounds was used. Patients were treated afterwards with three 500 mg intravenous pulses of methilprednisolone. RESULTS: A mean of 44.8% of synovial cells (range 30.1-62.8%) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methylprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. CONCLUSIONS: The lack of association between glucocorticoid receptor concentrations and clinical response could be due to the large steroid dose used, that saturated all available receptors. 相似文献
94.
RS Veazey DW Horohov JL Krahenbuhl HW Taylor JL Oliver TG Snider 《Canadian Metallurgical Quarterly》1995,47(1-2):79-87
Susceptibility of C57BL/6 (Bcgs) and C3H/HeN (Bcgr) mice to an intraperitoneal infection with Mycobacterium paratuberculosis strain 19698 was compared (by histopathology and the number of mycobacteria isolated from the spleen). Mycobacterial counts from the spleen of Bcgr mice progressively decreased over the course of infection but remained unchanged in Bcgs mice. Granulomatous lesions and acid-fast bacteria were consistently present in the liver and lymph nodes of Bcgs mice, whereas lesions were transient or absent in Bcgr mice. These results indicate that Bcgr mice are inherently resistant to M. paratuberculosis, whereas Bcgs mice are inherently susceptible. These differences may prove useful in elucidating the mechanisms of resistance and susceptibility to paratuberculosis and other mycobacterial infections. 相似文献
95.
Grant McClelland Georges Zwingelstein C. Richard Taylor Jean-Michel Weber 《Lipids》1995,30(2):147-153
The goals of this study were to determine: (i) whether mammals mobilize particular nonesterified fatty acids (NEFA) preferentially
during locomotion, (ii) if differences in aerobic capacity or diet can affect the pattern of NEFA mobilization and (iii) which
individual NEFA are most representative of total NEFA concentration changes, to use them as tracers for turnover studies.
Individual NEFA were measured in trained dogs and goats (VO2max dog/VO2max goat=2.2; where VO2max=max-imal oxygen consumption) during treadmill exercise at 40 and 60% VO2max. Important interspecies differences in individual NEFA concentrations could be attributed to differences in aerobic capacity.
The more aerobic species (dog) had much higher plasma NEFA concentrations for all but one NEFA (18∶0), when compared with
the low-aerobic species (goat). In addition, exercise caused a large increase in concentration of individual NEFA in the dogs,
with the largest increases seen in 18∶1 (150% above resting values) and 16∶0 (60% increase), but it had no effect in goats.
Therefore, the aerobic species has a much higher ability for mobilizing and transporting NEFA in plasma than its low-aerobic
counterpart. Two NEFA accounted for more than half total plasma NEFA in both species, 18∶1 (about 35% total NEFA) and 16∶0
(20%). Calculation of variability in percent composition reveals that oleate and palmitate also closely reflect changes in
total NEFA and are therefore the most appropriate tracers forin vivo kinetic studies in exercising mammals. Differences in diet and digestion physiology explained some differences in the plasma
NEFA composition of the two species; this was reflected in the percent contributions of individual fatty acids to total NEFA:
in dogs 18∶1>16∶0>18∶2>18∶0, while in goats 18∶1>16∶0>18∶0>18∶2. Also, only goats had 18∶3 (6% total NEFA), a fatty acid of
plant origin, while only dogs had 16∶1 (7% total NEFA). Overall, however, the plasma NEFA composition of goats did not exactly
reflect that of their diet due to preabsorptive modification of unsaturated fatty acids, while in dogs there was a good correlation
between dietary and plasma NEFA. 相似文献
96.
Gluconobacter oxydans possesses a unique organization of metabolic systems, which are characterized by reduction of major dissimilation pathways, surface localization of main oxidative enzymes responsible for partial oxidation of carbon substrates, high performance of electron-transport chains, and accumulation of partially oxidized metabolites in the medium. These features allow us to use the cells of these microorganisms in biotechnology for production of several food products and medicines. The use of G. oxydans in biosensors for estimation of concentrations of sugars, aldoses and polyalcohols is promising. Physiological and biochemical features of these microorganisms enabling their use in biotechnology and receptor elements of biosensors are reviewed. 相似文献
98.
目前反倾岩质边坡弯曲倾倒破坏分析方法仍以基于极限平衡理论的悬臂梁模型为主,但大多未考虑坡脚岩层的剪切破坏。为准确评价该类边坡的稳定性,建立考虑坡脚岩层剪切破坏的分析计算方法。首先,根据岩层变形破坏特征,将边坡分为后缘稳定区、中部弯曲倾倒区和前缘剪切区3个区域;其次,建立弯曲倾倒-剪切滑移破坏模式的稳定性分析方法;最后,通过工程实例验证,并进行参数分析。研究结果表明:提出的分析方法与工程实际符合性较好;边坡在倾角较陡、坡角较大时稳定性最差,坡角对边坡稳定性影响大于岩层倾角的影响;岩层厚度及层面内摩擦角增加有利于边坡稳定性,且会扩大坡脚剪切区范围。研究成果对反倾岩质边坡破坏的防治具有实践指导意义。 相似文献
99.
An opportunity arose in 1985 to become involved in a transition of working practice from hard copy to VDT. Over a two-year period, 161 VDT users and 65 control subjects in the same office environment were regularly and routinely examined for symptoms of asthenopia. The analysis of data shows that there are no significant differences in type, number and frequency of the work-related symptoms between VDT users and non-VDT users. It appears that reporting of symptoms within the group may be random, although certain symptoms do appear more frequently than others. Additionally, it appears that there is a significant difference between male and female users in the frequency of symptom reporting. 相似文献
100.