A binding study of phospholipase A2 with lecithin,lysolecithin and their tetrahedral intermediates using molecular modeling

We used molecular modeling to examine the binding of 1, 2-dioctanoyl-sn-glycero-3-phosphocholine (a lecithin), 1-octanoyl-sn-glycero-3-phosphocholine (a lysolecithin) and their tetrahedral intermediates in the catalytic site of phospholipase A₂ (PLA₂). We performed energy minimization on each complex, computed the binding energy, determined the relative binding energy among the complexes and calculated the difference in inter- and intramolecular energies of the components in the complexes. We found that the calculated orientation of the sn-1 ester bond of lysolecithin in the active site is similar to that of the sn-2 ester bond in lecithin, thus permitting PLA₂ to hydrolyze lysolecithin using the same mechanism as it uses to hydrolyze lecithin. On the other hand, the binding of lecithin is energetically more favorable by 4.5 kcal/mol than the binding of lysolecithin to the enzyme, and the binding of the lecithin tetrahedral intermediate is also energetically more favorable by 19.7 kcal/mol than the binding of the lysolecithin tetrahedral intermediate to the enzyme, which explains why lecithin is a better substrate than lysolecithin in the catalytic site. These results indicate that the activation energy for the hydrolysis of lysolecithin is higher than that for lecithin, consistent with the observed slower rate for the hydrolysis of lysolecithin.     

Inadequate dietary magnesium intake increases atherosclerotic plaque development in rabbits

Epidemiological studies have shown dietary magnesium (Mg) intake and serum Mg levels to be inversely correlated with the development of atherosclerosis. We hypothesized that low levels of Mg would promote atherosclerotic plaque development in rabbits. New Zealand white rabbits (4 months old, n = 22) were fed an atherogenic diet containing 0.12% (−Mg), 0.27% (control), or 0.43% (+Mg) Mg for 8 weeks. Blood samples were obtained at baseline, 2, 4, 6, and 8 weeks and were assayed for total cholesterol, high-density lipoprotein (HDL), non-HDL, triglycerides (TG), C-reactive protein, serum Mg, and erythrocyte Mg. Aortas from −Mg had significantly more plaque, with an intima thickness 42% greater than control and 36% greater than +Mg. Serum cholesterol levels rose over time, and at 8 weeks, −Mg had the highest and +Mg the lowest total and non-HDL cholesterol and TG levels, although these results did not reach significance. Over time, serum Mg levels increased, and erythrocyte Mg levels decreased. C-reactive protein significantly increased in all groups at 4 and 6 weeks but returned to baseline levels by 8 weeks. This study supports the hypothesis that inadequate intake of Mg results in an increase in atherosclerotic plaque development in rabbits.     

Dielectric Analysis of Phosphorylcholine Head Group Mobility in Egg Lecithin Liposomes

Purpose. A knowledge of the interfacial properties of lecithin underpins our understanding of many of the physicochemical characteristics of drug delivery systems such as liposomes and lecithin stabilized microemulsions. In order to further this understanding, a high frequency dielectric study of the interfacial properties of egg lecithin liposomes was undertaken. Methods. The effect of temperature, lecithin concentration and probe sonication on the interfacial dielectric properties of liposomal suspensions was investigated by high frequency dielectric relaxation spectroscopy between 0.2–6 GHz. Results. The frequency dependent permittivity of each suspension exhibited a dielectric dispersion centred around 100 MHz, corresponding to the relaxation of zwitterionic head groups. The activation energy for head group reorientation was estimated as H = 6.3 kJ mol^–1. There was an increase in extent of inter-head group interactions on increasing the liposome volume fraction, whereas the effect of probe sonication showed that: (i) head groups in both the outer and inner lamellae contribute to the dielectric response; (ii) the head groups may be less restricted in liposomes of high surface curvature with few lamellae; (iii) the high frequency permittivity of the suspension increased on sonication, as a result of a reduction in the amount of (depolarized) interlamellar water following a reduction in the number of lamellae per liposome. Conclusions. Dielectric analysis of the zwitterionic head groups of lecithin therefore provides a means for investigating the surface of lecithin liposomes, and may be used to investigate the effect of drugs and other solutes on membranes.     

利多卡因——卵磷脂微乳处方的初步研究

目的 :以卵磷脂微乳为载体 ,制备利多卡因透皮给药系统。方法 :伪三元相图考察油包水型微乳形成区域 ;测定微乳黏度 ,正交分析法筛选微乳处方 ;紫外分光光度法直接测定微乳中盐酸利多卡因浓度。结果 :助表面活性剂的种类和Km(表面活性剂 /助表面活性剂用量比 )对微乳形成区域有显著性影响 ,正丙醇和异丙醇所形成的微乳区较大 ;低纯卵磷脂微乳形成区域较高纯卵磷脂大 ;醇的种类对微乳的黏度均有显著的影响 ,Km 对微乳的黏度有较大影响。选定紫外检测波长为 2 6 2nm ,盐酸利多卡因浓度在 0 .0 2～ 0 .5mg/mL范围内线性关系良好 (R =0 .9999)。平均回收率 ( 10 0 .17± 0 .16 ) %。日内差与日间差分别为 0 0 137±0 0 12 1,0 0 119± 0 0 115。结论 :选择混合表面活性剂利于制备微乳 ,醇的种类与用量对于利多卡因透皮微乳体系处方的选择具有重要意义。     

大豆卵磷脂对酒精性肝损伤保护作用实验研究

目的：研究大豆卵磷脂对小鼠酒精性肝损伤的保护作用。方法：将动物随机分成阴性对照组、肝损伤阳性对照组及低、中、高三个剂量组，剂量组每天灌胃给予大豆卵磷脂。30天后，肝损伤阳性组及剂量组一次灌胃给予50％乙醇12ml／kg，禁食12小时处死动物，取动物肝脏，测定肝匀浆液MDA、GSH—PX、TG量，肝脏冰冻切片，苏丹Ⅲ染色后，进行病理组织学检查。结果：与肝损伤阳性组比较，低、高剂量组的MDA含量降低，各剂量组的GSH—PX含量升高，各剂量组冰冻病理学组织切片观察到脂肪变性评分低于肝损伤阳性组，差异均有显著性。结论：大豆卵磷脂对酒精性肝损伤具有保护作用。     

Influence of large molecular polymeric pigments isolated from fermented Zijuan tea on the activity of key enzymes involved in lipid metabolism in rat

Influence of large molecular polymeric pigments (LMPP) isolated from fermented Zijuan tea on the activity and mRNA expression of key enzymes involved in lipid metabolism in rat was explored. The results show that intragastric infusion of high-dose LMPP (1.215g/kg body weight) effectively suppressed the elevation in TC and LDL-C (p<0.05), and prevented the reduction in HDL-C (p<0.05), compared with the hyperlipidemia model group. LMPP significantly enhanced the activity of HL and HSL, and increased the HSL mRNA expression in the liver tissue and adipose tissue. High-LMPP treatment significantly reduced the HMG-CoA reductase expression by 56.5% in the liver compared with hyperlipidemia model group. In contrast, LDL-R expression was increased by 120% in the presence of high-LMPP treatment. These results suggest that LMPP have the hypolipidemic effect to some extent and significantly enhance HSL mRNA expression in the liver and adipose tissue, thereby increasing HSL activity in rat.     

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm^® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm^® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm^® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm^®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm^®, and the skin retention of the probe was the main determinant of its skin flux.     

葛根素联合卵磷脂络合碘片对眼底出血患者止血效果的影响

目的:探究葛根素联合卵磷脂络合碘片对眼底出血患者止血效果的影响。方法:选取2016-04/2017-03在我院就诊的眼底出血患者66例100眼,使用完全随机法将患者随机分为A组和B组,各33例50眼。A组给予卵磷脂络合碘片治疗,B组使用葛根素联合卵磷脂络合碘片治疗。两组均接受3个疗程的治疗。检测治疗前后血浆黏度指标、血清同型半胱氨酸(Hcy)、总胆固醇(TC)和甘油三酯(TG)水平变化,统计两组患者眼底出血治疗效果和不良反应发生率。结果:治疗前两组患者血浆黏度、血清Hcy、TC和TG指标无差异(P>0.05)。治疗后,两组患者的全血黏度高切、全血黏度低切、血浆黏度、Hcy、TC和TG均低于治疗前(P<0.001);与A组比较,B组患者全血黏度高切、全血黏度低切、血浆黏度、Hcy、TC和TG均降低(P<0.05)。B组患者较A组治疗总有效率增高(P<0.05)。两组患者均发生不同程度的甲状腺变化、胃肠道反应、精神兴奋和腹胀,两组患者不良反应生率无差异(P>0.05)。结论:葛根素联合卵磷脂络合碘片治疗眼底出血患者疗效显著,与改善患者血浆黏度、降低血清Hcy、TC和TG有关。     

激光光凝眼底联合卵磷脂络合碘片治疗中心性浆液性脉络膜视网膜病变99例疗效观察

目的评价激光光凝眼底联合卵磷脂络合碘片治疗中心性浆液性脉络膜视网膜病变(CSC)的疗效。方法将198例CSC患者212眼根据患者自愿分为两组各99例106眼。对照组采用激光光凝眼底治疗,观察组采用激光光凝眼底联合卵磷脂络合碘片治疗。在治疗1个月和3个月后用Amsler方格表评价视力恢复状况,并比较两组疗效。结果两组治疗后视力较之治疗前明显改善(P<0.05)。观察组治疗1月后视力恢复状况明显好于对照组(P<0.05),3月后两组视力无统计学差异(P>0.05)。观察组总显效率与对照组相比有统计学差异(P<0.05),但总有效率组间无统计学差异(P>0.05)。结论激光光凝眼底联合卵磷脂络合碘片治疗CSC可以帮助患者尽快改善视力状况,提升治疗总显效率,是一种较为理想的治疗手段,值得在临床中推广运用。