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121.
Dr. Jagadeesh Yerri Dr. José Dias Dr. Mallikajurna Reddy Nimmakayala Franck Razafindrainibe Charlotte Courageux Anne-Julie Gastellier Johanne Jegoux Dr. Caroline Coisne Dr. Christophe Landry Dr. Fabien Gosselet Johan Hachani Dr. Jean-François Goossens Prof. Marie-Pierre Dehouck Dr. Florian Nachon Dr. Rachid Baati 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(65):15035-15044
Novel 6-alkyl- and 6-alkenyl-3-fluoro-2-pyridinaldoximes have been synthesised by using a mild and efficient chemoselective hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime scaffolds, without altering the reducible, unprotected, sensitive oxime functionality and the C−F bond. These novel 6-alkyl-3-fluoro-2-pyridinaldoximes may find medicinal application as antidotes to organophosphate poisoning. Indeed, one low-molecular-weight compound exhibited increased affinity for sarin-inhibited acetylcholinesterase (hAChE) and greater reactivation efficiency or resurrection for sarin-inhibited hAChE, compared with those of 2-pyridinaldoxime (2-PAM) and 1-({[4-(aminocarbonyl)pyridinio]methoxy}methyl)-2-[(hydroxyimino)methyl]pyridinium chloride (HI-6), two pyridinium salts currently used as antidote by several countries. In addition, the uncharged 3-fluorinated bifunctional hybrid showed increased in vitro blood–brain barrier permeability compared with those of 2-PAM, HI-6 and obidoxime. These promising features of novel low-molecular-weight alkylfluoropyridinaldoxime open up a new era for the design, synthesis and discovery of central non-quaternary broad spectrum reactivators for organophosphate-inhibited cholinesterases. 相似文献
122.
A simple, sensitive and rapid assay method has been developed and validated as per regulatory guidelines for the estimation of enasidenib on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The method employs liquid extraction of enasidenib from DBS disks of mouse whole blood followed by chromatographic separation using 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 1.0 mL/min on an Atlantis dC18 column with a total run time of 2.0 min. The MS/MS ion transitions monitored were m/z 474.0 → 267.1 for enasidenib and m/z 309.2 → 251.3 for the internal standard (warfarin). The assay was linear in the range of 1.01 – 3044 ng/mL. The within‐run and between‐run precisions were in the range of 3.18 – 9.06 and 4.66 – 8.69%, respectively. Stability studies showed that enasidenib was stable on DBS cards for 1 month. This novel method has been applied to analyze the DBS samples of enasidenib obtained from a pharmacokinetic study in mice. 相似文献
123.
An inflatable cuff wrapped around the upper arm is widely used in noninvasive blood pressure measurement. However, the mechanical interaction between cuff and arm tissues, a factor that potentially affects the accuracy of noninvasive blood pressure measurement, remains rarely addressed. In the present study, finite element (FE) mod-els were constructed to quantify intra-arm stresses generated by cuff compression, aiming to provide some theoretical evi-dence for identifying factors of importance for blood pressure measurement or explaining clinical observations. Obtained results showed that the simulated tissue stresses were highly sensitive to the distribution of cuff pressure on the arm sur-face and the contact condition between muscle and bone. In contrast, the magnitude of cuff pressure and small variations in elastic properties of arm soft tissues had little influence on the efficiency of pressure transmission in arm tissues. In par-ticular, it was found that a thickened subcutaneous fat layer in obese subjects significantly reduced the effective pres-sure transmitted to the brachial artery, which may explain why blood pressure overestimation occurs more frequently in obese subjects in noninvasive blood pressure measurement. 相似文献
124.
《Analytical letters》2012,45(5):441-450
Abstract A microcell has been constructed for stripping analysis in solution volumes as low as 5 μl, employing a glassy carbon or mercury-plated glassy carbon working electrodes and a three electrode system. Using normal d.c. stripping techniques, as little as 100 picograms of mercury and 10 picograms of lead can be determined. With the more sensitive second harmonic a.c. voltammetric technique, this limit is lowered to 10 picograms of mercury and 1 picogram of lead. 相似文献
125.
目的研究胎儿脐带血中的铅与钙、锌、铁的含量以及两两之间的相关性。方法采用原子吸收光谱法对398例脐带血铅和钙、锌、铁的含量进行测定,并对它们进行相关性分析。结果 398例脐带血铅和钙、锌、铁的质量浓度分别为铅(37.96±17.78)μg/L、钙(1.51±0.29)mmol/L、锌(30.01±11.14)μmol/L、铁(8.63±1.39)mmol/L。线性回归分析显示:铅与钙(r=-0.563,P0.01)、铅与锌(r=-0.424,P0.01)有相关性,铅与铁无显著相关(r=0.018,P0.05)。结论随着胎儿体内血铅水平的上升,二价元素钙、锌含量有下降趋势,即中毒元素铅会干扰胎儿体内的必需二价元素的代谢。 相似文献
126.
《Biomedical chromatography : BMC》2017,31(12)
Typhae Pollen, dried pollen of Typha angustifolia L., Typha orientalis Presl or other plants of the same genus (Typhaeceae), has the effect of activating the circulation to cure blood stasis in traditional Chinese Medicine. The purpose of this study was to set up an ultra‐high performance liquid chromatography method that could determine p‐ hydroxybenzoic acid and vanillic acid simultaneously in rat plasma, and to compare their pharmacokinetics in normal rats and rats with acute cold blood stasis, and further to investigate the influence of different dosages of oral administration. The pharmacokinetic parameters obtained showed that both of the phenolic acids had a higher bioavailability in rats with cold blood stasis than that in normal rats with a higher area under the concentration–time curve and longer mean residence time, and the high dose oral administration group had a higher capacity in blood stasis rats than in normal rats. These results reminded us that changes in health condition could alter the absorption and elimination of both phenolic acids in vivo , and the pharmacokinetic study under pathological conditions provides important information for more rational drug use in clinical situations. 相似文献
127.
Khazangul A. Ibrahimova Abdulsaid A. Azizov Ofeliya O. Balayeva Rasim M. Alosmanov Sevinj C. Mammadyarova 《Mendeleev Communications》2021,31(1):100-103
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128.
We study the well-posedness of a system of one-dimensional partial differential equations modeling blood flows in a network of vessels with viscoelastic walls. We prove the existence and uniqueness of maximal strong solution for this type of hyperbolic/parabolic model. We also prove a stability estimate under suitable nonlinear Robin boundary conditions. 相似文献
129.
130.
The hindered monomer, 2,3,4-trimethyl-3-pentyl methacrylate (I), was synthesized for penultimate effect studies. Since it readily homopoiymerized (km111≠ 0) and readily copolymerized with styrene, copolymerizations of I with styrene were carried out at 60°C in benzene with AIBN as initiator. The conversion to copolymer and the copolymer composition were determined by using GLC techniques. Composition-conversion data was analyzed by performing a computerized nonlinear least-squares fitting to the integrated form of the penultimate model equation. The experimental design included the use of optimized M1°/M2° ratios. The penultimate reactivity ratios calculated from these data were r1′ = 0.23, r1′= 0.59, r2 = 0.59, r2′ = 1.34. Thus, when I is the penultimate unit, a terminal styryl radical prefers to add styrene, whereas when styrene is the penultimate unit, terminal styryl radicals prefer to add I. These results constitute the best evidence for a steric penultimate effect yet available in the literature from composition-conversion studies. However, the case is not yet proved. Further studies to strengthen this conclusion are proposed. 相似文献