PubMed · 14876524
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A McMAHON, H N ALLEN, C J WEBER, W C MISSEY. 1951. Hypercholesterolemia.. https://doi.org/10.1097/00007611-195111000-00001
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We show in this study that stable dispersions dominated by flat bilayer disks may be prepared from a carefully optimized mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-5000] [PEG-DSPE(5000)]. By varying the content of the latter component, the average diameter of the disks can be changed in the interval from about 15 to 60 nm. The disks show excellent long-term stability, and their size and structure remain unaltered in the temperature range between 25 and 37 degrees C. The utility of the disks as artificial model membranes was confirmed and compared to uni- and multilamellar liposomes in a series of drug partition studies. Data obtained by isothermal titration calorimetry and drug partition chromatography (also referred to as immobilized liposome chromatography) indicate that the bilayer disks may serve as an attractive and sometimes superior alternative to liposomes in studies aiming at the investigation of drug-membrane interactions. The disks may, in addition, hold great potential for structure/function studies of membrane-bound proteins. Furthermore, we suggest that the sterically stabilized bilayer disks may prove interesting as carriers for in vivo delivery of protein/peptide, as well as conventional amphiphilic and/or hydrophobic, drugs.
An efficient (89-95% yield) and low-cost procedure to prepare unilamellar vesicles was used to incorporate zinc phthalocyanine (ZnPc), a model compound used as a phototherapeutic agent in studies aiming the use of unilamellar vesicles as delivery system for photodynamic therapy (PDT). ZnPc was incorporated in the presence or absence of cholesterol (CHOL), which improved the stability of the delivery system. The net vesicles present a mean diameter around 1000 nm, whereas in the presence of CHOL, CHOL and ZnPc, or only ZnPc, a drastic reduction in its diameter, varying between 100 and 150 nm, was observed. The incorporation of only ZnPc also results in a considerable reduction in the diameter of the liposomes suggests that ZnPc, due to its high hidrophobicity, must share the same microenvironment occupied by CHOL molecules.
AIMS: Our aim was to evaluate the usefulness of the total cholesterol/HDL-cholesterol ratio (TC/HDL) in predicting the cardiovascular risk of Type 2 diabetic patients. METHODS: Prospective cohort study with inclusion of 418 Type 2 diabetic individuals with follow-up until the appearance of a cardiovascular event. The predictive power of updated mean lipid values during follow-up was analysed by means of Cox proportional hazard models. An estimate was made of the relative risk (RR) conferred by high levels of TC/HDL stratified by LDL-cholesterol levels. RESULTS: Sixty-six cardiovascular events occurred during an average follow-up of 4.7 years (sd 1.5). The main lipid predictor of vascular events was mean TC/HDL ratio [hazard ratio (HR) = 1.46; 95% confidence interval (CI) 1.25, 1.7; P < 0.0001]. In the multivariate model with simultaneous inclusion of mean TC/HDL and mean LDL-cholesterol, both were significant predictors of cardiovascular disease [HR (1 unit) = 1.37; 95% CI 1.16, 1.62; P = 0.0003 and HR (1 mmol/l) = 1.5; 95% CI 1.04, 2.18; P = 0.03, respectively]. The LDL adjusted RR for cardiovascular events due to high TC/HDL ratio, with 4.5 cut-off point, was 2.5 (95% CI 1.4, 4.3; P = 0.0007). For the stratum of subjects with average LDL cholesterol < 3.5 mmol/l, RR was 1.2 (95% CI 0.5, 2.8; P = NS) and for the stratum of average LDL cholesterol > 3.5 mmol/l, RR was 4 (95% CI 1.8, 9; P = 0.00013), with heterogeneity among strata (P = 0.044). CONCLUSIONS: It could be useful to include the TC/HDL ratio in treatment guides for diabetic dyslipidaemia, given their high predictive value and strong interaction with LDL cholesterol.