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41.
Several approaches to the separation of four stereoisomers, 1–4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5–8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1–4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-l-(l-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5-dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1–4 or 5–8. The details of chiral separations using various methods and separation () and capacity factors (k) of the derivatized isomers 1–8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S
1
S
2 (5), and the heat (HD) and light (LD) degradation products of 1 as R
1
S
2 (3) and S1
S
2 (5), respectively. 相似文献
42.
十二烷基硫酸钠在天然水体中的降解作用 总被引:1,自引:0,他引:1
本文研究了十二烷基硫酸钠在天然水体中的降解作用,结果表明十二烷基硫酸钠在天然水体中的降解主要依赖于微生物的降解。微生物最适降解条件为pH6.5~9.4和36℃左右。降解作用随温度升高(4~36.5℃)和微生物浓度增大而加快,用十二烷基硫酸钠预先驯化微... 相似文献
43.
为评价部分平均通过时间(MTTp)和F-V曲线形状对检查吸烟者小气道功能的临床意义,作者对116例被动和轻、重度主动吸烟者进行了常规肺通气功能、MTTp和F-V曲线形状的探讨。常规肺通气功能和F-V曲线形状用常规法测定。MTTp用“简易计算法”公式计算。结果显示凸型F-V曲线的分布随吸烟程度而上升。·V50、·V25下降及MTT45%~55%、MTT70%~80%延长在凸型与重度吸烟组一致。MTT45%~55%与MTT70%~80%延长的范围在两者都是预计值的110%~120%,表明小气道功能已有轻度障碍。因而凸型F-V曲线、MTT45%~55%及MTT70%~80%延长、·V50、·V25下降都是检查小气道功能的敏感指标。用“简易计算法”计算MTTp简便准确,宜于临床推广应用 相似文献
44.
Harro J Pähkla R Modiri A-R Harro M Kask A Oreland L 《Journal of neural transmission (Vienna, Austria : 1996)》1999,106(7-8):619-629
Summary. DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals originating from the locus coeruleus. Preliminary
data suggested that its effect in a typical screening test for antidepressant drugs, the forced swimming test, is biphasic
dependent on the dose. In the present study, DSP-4 was administered in four doses (5, 10, 30 and 50 mg/kg) to male Wistar
rats. Administration of the neurotoxin had a dose-dependent biphasic effect on immobility time in the forced swimming test
8 and 9 days later. Thus, DSP-4 at the dose of 10 mg/kg increased immobility, but higher doses reduced this measure. The reduction
of noradrenaline concentration in the frontal cortex and hippocampus was dose-dependent starting from the dose 10 mg/kg. Cortical
β-adrenoceptor binding was increased by DSP-4 treatment at the doses 30 mg/kg and 50 mg/kg. These results suggest that the
increase in immobility time in the forced swimming test is associated with presynaptic changes in noradrenaline availability,
whereas the decrease in immobility observed after more complete denervation is associated with postsynaptic receptor supersensitivity.
Received September 2, 1998; accepted February 2, 1999 相似文献
45.
Marianne Dalene Kristina Jakobsson Agneta Rannug Gunnar Skarping Lars Hagmar 《International archives of occupational and environmental health》1996,68(3):165-169
The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r
s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r
s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA. 相似文献
46.
Summary Six patients with recently ruptured intracranial aneurysms were treated preoperatively with tranexamic acid (AMCA). Two patients received 6 g daily in i.v. infusion, two had 6 g daily by i.v. injection, and two patients were given AMCA 9 g daily by mouth during the first week after bleeding. Serial assays of AMCA and fibrin/fibrinogen degradation products (FDP) in cerebrospinal fluid (CSF) were performed during 6–13 days after the initial subarachnoid haemorrhage (SAH). Judged from the decline in CSF-FDP, an assumed therapeutic level of 1 mg/l of AMCA in CSF was reached within 24–36 hours after the first dose when the drug was administered intravenously and within 48 hours when the drug was given orally. 相似文献
47.
S. A. Volgushev V. A. Kosykh E. A. Podrez D. K. Novikov S. M. Khlynin R. S. Karpov 《Bulletin of experimental biology and medicine》1991,111(3):313-315
Research Institute of Cardiology, Tomsk Scientific Center, Academy of Medical Sciences of the USSR. Research Institute of Experimental Cardiology, All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 3, pp. 254–256, March, 1991. 相似文献
48.
The effects of urokinase on ADP breakdown by vessel-wall, platelet aggregation and the related prostaglandin system "in vitro" were investigated. It is confirmed that urokinase does not induce platelet aggregation both in humans and rabbits "in vitro". Conversely, in high concentrations, urokinase inhibits ADP-induced platelet aggregation in human and rabbit platelet-rich plasma. No effects were observed on rabbit platelet thromboxane A2 release and on rat vascular prostacyclin production, both measured by radioimmunoassay of thromboxane B2 and 6-keto-F1 alpha prostaglandin, respectively. Moreover, the incubation of urokinase with vascular endothelium resulted in an increased disappearance rate. 相似文献
49.
局部炎症反应与无细胞异种真皮基质移植物的降解吸收关系 总被引:2,自引:1,他引:2
目的 探讨不同方法制作的无细胞异种真皮基质(Xeno-ADM)移植物降解吸收与炎症反应之间的关系。方法 猪和兔断层中厚皮片经Trypsin和TritonX-100等脱细胞,分别制成Xe-no-ADM和异体ADM(Allo-ADM),再按不同的预处理因素进行分组:(1)戊二醛交联的Xeno-ADM(A)组;(2)网状交联的Xeno-ADM(B)组;(3)未交联的:Xeno-ADM(C)组,预先被Xeno-ADM蛋白致敏的兔皮下植入;(4)交联的Xeno-ADM(D)组;(5)Allo-ADM(E)组。每组80块ADM分别埋植于兔耳和背部皮下。结果在背部的移植物较耳部炎性反应和降解吸收明显,至术后32wk时,E组以外的其它组移植物解剖学和组织学结构消失,D组和A组炎症反应滞后,可见较多的异物巨细胞,各组ADM炎症反应与降解/吸收的程度依次为:C>B>D>A>E(P相似文献
50.