Classification Analysis of P-Glycoprotein Substrate Specificity

Prediction of P-glycoprotein substrate specificity (S_PGP) can be viewed as a constituent part of a compound's “pharmaceutical profiling” in drug design. This task is difficult to achieve due to several factors that raised many contradictory opinions: (i) the disparity between the S_PGP values obtained in different assays, (ii) the confusion between Pgp substrates and inhibitors, (iii) the confusion between lipophilicity and amphiphilicity of Pgp substrates, and (iv) the dilemma of describing class-specific relationships when Pgp has no binding sites of high ligand specificity. In this work, we compiled S_PGP data for 1000 compounds. All data were represented in a binary format, assigning S_PGP=1 for substrates and S_PGP=0 for non-substrates. Each value was ranked according to the reliability of experimental assay. Two data sets were considered. Set 1 included 220 compounds with S_PGP from polarized transport across MDR1 transfected cell monolayers. Set 2 included the entire list of 1000 compounds, with S_PGP values of generally lower reliability. Both sets were analysed using a stepwise classification structure–activity relationship (C-SAR) method, leading to derivation of simple rules for crude estimation of S_PGP values. The obtained rules are based on the following factors: (i) compound's size expressed through molar weight or volume, (ii) H-accepting given by the Abraham's β (that can be crudely approximated by the sum of O and N atoms), and (iii) ionization given by the acid and base pK_a values. Very roughly, S_PGP can be estimated by the “rule of fours”. Compounds with (N+O)≥8, MW>400 and acid pK_a > 4 are likely to be Pgp substrates, whereas compounds with (N+O)≤4, MW<400 and base pK_a<8 are likely to be non-substrates. The obtained results support the view that Pgp functioning can be compared to a complex “mini-pharmacokinetic” system with fuzzy specificity. This system can be described by a probabilistic version of Abraham's solvation equation, suggesting a certain similarity between Pgp transport and chromatographic retention. The chromatographic model does not work in the case of “marginal” compounds with properties close to the “global” physicochemical cut-offs. In the latter case various class-specific rules must be considered. These can be associated with the “amphiphilicity” and “biological similarity” of compounds. The definition of class-specific effects entails construction of the knowledge base that can be very useful in ADME profiling of new drugs.     

江香薷的极性成分研究Ⅱ

目的:对江香薷的较大极性部分的化学成分进行分离鉴定.方法:运用柱色谱和高效液相进行分离纯化,通过理化性质和波谱分析鉴定结构.结果:从中分离得到了7个苷类化合物,分别鉴定为4-羟基-2,6二甲氧基苯基-β-D-吡喃葡萄糖苷(1),4-羟基-3.5二甲氧基苯基-β-D-吡喃葡萄糖苷(2),3,4,5-三甲氧基苯基-β-D-吡喃葡萄糖苷(3),3-hydroxyestragole-β-D-glucopyranoside(4),(6S,9R)-长寿花糖苷(5),腺苷(6),对羟基苯甲酸-β-D-吡喃葡萄糖苷(7).结论:化合物1～7均为首次从该属植物中分离得到.     

宁夏大蓟提取物不同极性部位对5种革兰阴性菌的体外抑菌活性研究

目的:观察宁夏大蓟提取物的不同极性部位对5种革兰阴性菌体外抑菌活性作用。方法:大蓟水提取物、大蓟正丁醇提取物、大蓟乙酸乙酯提取物用试管二倍稀释法联合琼脂平板法,进行体外抑菌试验研究。结果:大蓟水提取物、大蓟乙酸乙酯提取物对5种革兰阴性菌最小抑菌浓度(MIC)均为﹥1.00 mg.mL-1;大蓟正丁醇提取物对5种革兰阴性菌有抑菌作用,对大肠杆菌、铜绿假单胞杆菌MIC均为1.0mg.mL-1;对伤寒沙门菌、变形杆菌、福氏痢疾杆菌MIC均为0.5mg.mL-1。结论:大蓟正丁醇提取物对5种革兰阴性菌有抑菌作用,大蓟水提取物、大蓟乙酸乙酯提取物无抑菌作用。     

Dietary conjugated linoleic acid isomers change the unsaturation degree of hepatic fatty acids in neutral lipids but not in polar lipids

The fatty acid composition of phospholipids plays a key role in the structural and functional properties of cellular membrane. In this study, it was hypothesized that conjugated linoleic acid (CLA) isomer supplementation changes the unsaturation degree of the fatty acids of neutral lipids (NLs) but not those of polar lipids (PLs). Thus, the main goal was to determine the pattern of fatty acid incorporation into hepatic PL and NL fractions. Wistar male rats were fed cis(c)9,trans(t)11 and t10,c12 CLA isomers, separately or as a mixture. Whereas the t10,c12 isomer incorporation in the PL fraction was similar when supplemented either individually or as a mixture, the c9,t11 isomer reached the highest values of incorporation when combined with t10,c12. In the PL fraction, the linoleic acid did not change; but the arachidonic acid decreased, especially in the rats given the mixture. Also in this fraction, the t10,c12 isomer, either separately or as a mixture, decreased the amounts of n-6 long-chain (LC) polyunsaturated fatty acids (PUFA) and increased those of the n-3 LC PUFA relative to the control. In the NL fraction, linoleic acid incorporation followed the diet composition, whereas the arachidonic acid was similar among treatments. Facing CLA isomer supplementation, the present study suggests that fatty acid incorporation into phospholipids, through the balance between n-6 and n-3 LC PUFA, is dependent upon maintaining the unsaturation degree of cellular membrane.     

后囊缺陷性白内障超声乳化术的临床观察

目的:探讨后囊缺陷性白内障手术方式,比较超声乳化技术和囊外摘除技术的安全性和效果。方法:回顾性分析后囊缺陷性白内障患者33例40眼的手术效果,囊外摘除手术组(ECCE组)10例12眼、超声乳化手术组(Phaco组)23例28眼。结果:后囊破裂+玻璃体脱出:ECCE组为3眼(25%),Phaco组为3眼(11%),两组比较有显著性差异(P<0.05)。术后矫正视力提高≥2行者:ECCE组为10眼(83%),Phaco组为26眼(93%),两组比较有显著性差异(P<0.05)。结论:对于后囊缺陷性白内障患者,超声乳化手术的安全性和效果优于囊外手术。超声乳化手术中,始终保持前房的稳定,不行水分离、在低流量、低负压、低能量下进行,正确处理后极部皮质与后囊膜的关系是手术成功的关键。     

后极性白内障高频超声图像分析

目的:利用高频超声检查,分析判断后极性白内障后囊膜是否存在先天性缺陷。方法:选择2016-2018年间,我院确诊并完成手术的15名后极性白内障患者的25只眼,术前进行25MHz高频B超检查,分析其图像资料,判断其后囊膜是否存在先天性异常,以指导白内障手术,并与术中发现进行比较分析。结果:15名患者25只手术眼中,术前判断后囊膜完整的22眼,判断后囊膜完整但不排除有粘连,后囊膜先天缺陷3眼。术中发现,后囊膜判断先天异常的3眼,后囊膜均出现破裂。后囊膜判断完整的病例术中后囊膜保持完整,但部分发生局限的粘连或混浊。结论:25MHz高频B超的应用可以在术前明确术中必定出现的后囊膜破裂病例,为针对性的术中处理和减少并发症创造了条件。     

后极性白内障的超声乳化手术治疗

目的:探讨后极性白内障的临床特点及超声乳化手术的手术技巧。方法:连续收集2009-10/2011-03在本院诊治的后极性白内障患者12例17眼,所有病例均接受详尽的病史采集,以及视力、裂隙灯显微镜检查,B型超声波及间接检眼镜检查,所有患眼在球周浸润麻醉下行超声乳化白内障摘除及折叠人工晶状体植入,总结手术技巧、术前术后视力及术中并发症。结果:所有患眼均植入折叠人工晶状体。术中11眼后囊膜完整透明,2眼后囊膜破裂,其中1眼发生在分核时,另1眼发生在核周壳吸除时;4眼术中发现后囊膜混浊需后期行YAG激光后囊膜切开术。15眼折叠人工晶状体植入囊袋内,2眼植入睫状沟。术后1mo最佳矫正视力≥0.5者16眼,0.4者1眼。结论:超声乳化联合折叠型人工晶状体植入是治疗后极性白内障安全有效的方法。应用连续环形撕囊、轻柔谨慎的水分层而不做水分离,低能量、低吸力、低流量的超声乳化参数设置,手动吸除核周壳和皮质等手术技巧,可以减少手术并发症。     

Probing the Use of Silane-Grafted Fumed Silica Nanoparticles to Produce Stable Transformer Oil-Based Nanofluids

In this experimental investigation, hydrophobic silane-grafted fumed nano-silica was employed in transformer oil to formulate nanofluids (NFs). A cold-air atmosphere-pressure plasma reactor working on the principle of dielectric barrier discharge was designed and utilized to functionalize the surface of these nanoparticles. A field emission scanning electron microscope (FE-SEM) coupled with energy-dispersive X-ray (EDX) module and Fourier transform infrared (FTIR) spectroscopy were used to scan surface features of new and plasma-treated nanoparticles. The study revealed considerable changes in the surface chemistry of nanoparticles, which led to good dispersibility and stability of nanofluids. The measurements of AC breakdown voltages (AC-BDV) of nanofluids so prepared were conducted according to IEC-Std 60156, and a significant improvement in the dielectric strength was achieved. A statistical analysis of these results was performed using Weibull probabilistic law. At a 5% probability of failure, modified nanofluid remarkably exhibited a 60% increase in breakdown voltage. The dielectric properties such as variation of εr and tan δ in temperature of up to 70 °C were measured and compared with untreated fluid. Results exhibit an increase in tan δ and a slight decrease in permittivity of nanofluids. The analysis also revealed that while unpolar silane coating of NPs increased the breakdown strength, the polar-amino-silane-coated NPs in oil resulted in a drastic reduction. Details of this antagonistic trend are elaborated in this paper.     

Inverse horse-shoe technique for the phacoemulsification of posterior polar cataract

Objective: To study a new technique of controlled hydrodelineation followed by viscodelineation and viscodissection during phacoemulsification in eyes with posterior polar cataracts and to report its effectiveness in preserving the posterior capsule.Design: Prospective interventional study.Participants: Twenty-eight eyes of 22 patients with posterior polar cataracts.Methods: All patients underwent phacoemulsification under topical anaesthesia with controlled hydrodelineation, viscodelineation, and viscodissection with minimal stress on the posterior capsule. Hydrodissection was not done. The preoperative complications and visual outcome were recorded.Results: The mean follow-up time was 8 months (range 2-24 months). Posterior capsule rupture occurred only in 2 eyes (7.1%); neither of the 2 had any vitreous prolapse, so anteriorvitrectomy was not required. Mean visual acuity improved significantly after surgery (p = 0.0001, paired t test). The causes of the low postoperative visual acuity were amblyopia in 3 eyes (10.7%) and age-related macular degeneration in 1 (3.6%).Conclusions: This inverse horse-shoe technique of controlled viscodelineation and viscodissection markedly reduced the risk of posterior capsule rupture. Moreover, if it occurred, the anterior vitreous face remained intact, so the IOL could be implanted in the sulcus without resorting to anterior vitrectomy.