PubMed · 13981463
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R F REINFRANK, W P CLASON. 1962. Serum cholesterol and thyroid function.. https://pubmed.ncbi.nlm.nih.gov/13981463/
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We have used high-resolution field-cycling 31P NMR spectroscopy to measure spin-lattice relaxation rates (R1 = 1/T1) of multicomponent phospholipid vesicle and micelle samples over a large field range, from 0.1 to 11.7 T. The shape of the curve for R1 as a function of field and a model-free analysis were used to extract tauc, a correlation time for each type of phospholipid molecule in the bilayer that is likely to reflect rotation of the molecule about the axis perpendicular to the membrane surface; Sc2, a chemical shift anisotropy (CSA) order parameter; and tauhf, a time constant reflecting faster internal motion. This 31P technique was also used to monitor association of a peripheral membrane protein, Bacillus thuringiensis phosphatidylinositol-specific phospholipase C, with both phosphatidylcholine and phosphatidylmethanol bilayers. Differences in phospholipid dynamics induced by the protein shed light on how zwitterionic phosphatidylcholine, and not the anionic phosphatidylmethanol, activates the enzyme toward its substrate.
BACKGROUND: Cardiovascular disease accounts for more than half the number of deaths among dialysis patients. The role of HMG CoA reductase inhibitors (statins) in the treatment of hyperlipidemia in dialysis patients is unclear and their safety has not been established. OBJECTIVES: To assess the benefits and harms of statins in peritoneal dialysis (PD) and hemodialysis patients (HD). SEARCH STRATEGY: We searched MEDLINE (1966-July 2003), EMBASE (1980-July 2003), the Cochrane Central Register of Controlled trials (CENTRAL, in The Cochrane Library - issue 2, 2004), the Cochrane Renal Group's specialized register (April 2004) and handsearched reference lists of textbooks, articles and scientific proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in dialysis patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model after testing for heterogeneity. The results were expressed as weighted mean difference (WMD) for continuous outcomes and relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Six studies involving 357 participants were identified - three studies had both continuous ambulatory peritoneal dialysis (CAPD) and HD participants, two included only HD participants and one study only included CAPD participants. Studies were all of short duration and morbidity and mortality were not assessed. Average total cholesterol decreased significantly with statins compared to placebo in all dialysis patients (WMD -53.70 mg/dL (1.40 mmol/L), 95% CI -66.95 to -40.54). Similarly, average LDL cholesterol decreased significantly with statins in comparison to placebo in all patients (WMD -55.40 mg/dL (1.44 mmol/L), 95% CI -69.90 to -40.90) as did average triglycerides (-33.72 mg/dL (0.37 mmol/L), 95% CI -54.16 to -13.28). There was a significant increase in average HDL cholesterol levels (WMD 4.84 mg/dL (0.13 mmol/L), 95% CI 0.28 to 9.40) with statins compared to placebo in HD but not in CAPD patients. One trial compared statins to the hypolidemic agent probucol and found no significant differences between the two treatment groups. REVIEWERS' CONCLUSIONS: Statins used for 12 weeks decreased cholesterol levels in dialysis patients similar to the general population. Included studies were of short duration and therefore the efficacy of statins in decreasing the cardiovascular, cerebrovascular events and mortality rates is still unclear. The safety of statins needs to be addressed in the current ongoing clinical trials.
Surface pressure-area isotherm, neutron specular reflection, and small-angle neutron scattering studies have been carried out to determine the effects of added cholesterol and distearoylphosphatidylcholine (DSPC), on the molecular structures of monolayers and vesicles containing the dialkyl polyoxyethylene ether surfactant, 1,2-di-O-octadecyl-rac-glyceryl-3-(alpha-dodecaethylene glycol) (2C18E12). Previous neutron reflectivity studies on 2C18E12 monolayers at the air/water interface have shown them to possess a thickness of approximately 24 angstoms and highly disordered structure with significant intermixing of the polymer headgroups and alkyl chains. SANS studies of 2C18E12 vesicles gave a bilayer thickness of approximately 51 angstroms. Addition of cholesterol to 2C18E12 monolayers (1:1 molar ratio), produced a marked condensing effect coupled with an increased the layer thickness of approximately 7 angstroms, and in vesicles, increased bilayer thickness by approximately 16 angstroms. Monolayers consisting of 2C18E12:DSPC:cholesterol (1:1:2 molar ratio), showed a layer thickness of approximately 31 angstroms, whereas in vesicles, three-component bilayer was found to be only approximately 9 angstroms thicker than those possessed by vesicles composed solely of 2C18E12. Mixing between the molecules in three-component monolayers was shown to be ideal through analysis of the neutron reflectivity data. These findings are discussed in relation to increased ordering and decreased headgroup/hydrophobe intermixing within both monolayers and vesicle bilayers containing 2C18E12. The inferred increase in molecular order within vesicles composed of 2C18E12 with additional cholesterol and phospholipid is used as a model for explaining theoretical differences in bilayer permeability.