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.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.     

Exercise training following myocardial infarction improves myocardial perfusion assessed by thallium-201 scintigraphy

AIM: We assessed the effects of a 6-week exercise programme on the thallium-201 myocardial perfusion characteristics of patients following myocardial infarction. METHODS: Twenty-five patients presenting with a first acute myocardial infarction were randomised into two groups: (i) those undergoing a supervised exercise training programme over 6 weeks (n=15) and (ii) a control group who did not attend the exercise programme (n=10). All underwent three sequential stress thallium myocardial perfusion scans at 10 days, 6 weeks and 3 months after infarction. The stress conditions were identical on each occasion. The images were analysed using a polar plot with a computer assisted algorithm comparing stress and redistribution data. Values for extent, severity and percentage redistribution of the thallium images were generated. RESULTS: A total of 29 perfusion defects were identified, 18 in the exercise group and 11 in the control group. Over 3 months in the exercise group the mean extent of the stress image defect fell from 109+/-64 to 95+/-51 pixels (P<0.05) while in the control group there was an increase from 133+/-57 to 144+/-57 pixels (P=ns). Stress defect severity fell in the exercise group from 581+/-417 to 494+/-346 S.D. (P<0.05) but increased in the control group from 765+/-494 to 877+/-543 S.D. (P=ns). On redistribution imaging in the exercise group a significant decrease was observed in both extent (94+/-56 to 76+/-43 pixels (P<0.05)) and severity (541+/-387 to 438+/-291 S.D. (P<0.05)) of the defects. However in the control group no significant change was observed for extent (125+/-54 to 125+/-52 pixels) or severity (745+/-485 to 820+/-503 S.D.) of the redistribution defects (P=ns). Reversibility of the defects increased slightly in both the exercise group (from 14.6+/-17 to 17.5+/-20%) and the control group (5.2+/-5 to 9.6+10%) (P=ns). CONCLUSION: Following myocardial infarction a 6-week exercise programme improves myocardial perfusion characteristics. An exercise programme should be integrated into cardiac rehabilitation protocols for patients after infarction.