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- Cans, Ann-Sofie, 1971, et al.
(författare)
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Positioning lipid membrane domains in giant vesicles by micro-organization of aqueous cytoplasm mimic
- 2008
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 130:23, s. 7400-7406
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Tidskriftsartikel (refereegranskat)abstract
- We report localization of lipid membrane microdomains to specific "poles" of asymmetric giant vesicles (GVs) in response to local internal composition. Interior aqueous microdomains were generated in a simple model cytoplasm composed of a poly(ethyleneglycol) (PEG)/dextran aqueous two-phase system (ATPS) encapsulated in the vesicles. The GV membrane composition used here was a modification of a DOPC/DPPC/cholesterol mixture known to form micrometer-scale liquid ordered and liquid disordered domains; we added lipids with PEG 2000 Da-modified headgroups. Osmotically induced budding of the ATPS-containing GVs led to structures where the PEG-rich and dextran-rich interior aqueous phases were in contact with different regions of the vesicle membrane. Liquid ordered (L-o) membrane domains rich in PEG-terminated lipids preferentially coated the PEG-rich aqueous phase vesicle "body", while coexisting liquid disordered (L-d) membrane domains coated the dextran-rich aqueous phase "bud". Membrane domain positioning resulted from interactions between lipid headgroups and the interior aqueous polymer solutions, e.g., PEGylated headgroups with PEG and dextran polymers. Heating resulted first in patchy membranes where L. and Ld domains no longer showed any preference for coating the PEG-rich vs dextran-rich interior aqueous volumes, and eventually complete lipid mixing. Upon cooling lipid domains again coated their preferred interior aqueous microvolume. This work shows that nonspecific interactions between interior aqueous contents and the membrane that encapsulates them can drive local chemical heterogeneity, and offers a primitive experimental model for membrane and cytoplasmic polarity in biological cells.
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- Olsson, Andes G., et al.
(författare)
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Effects of High-Dose Atorvastatin in Patients =65 Years of Age With Acute Coronary Syndrome (from the Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering [MIRACL] Study)
- 2007
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 99:5, s. 632-635
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Tidskriftsartikel (refereegranskat)abstract
- After acute coronary syndromes (ACSs), older patients are particularly susceptible to early complications, including death and recurrent ACS. Lipid management guidelines do not differentiate elderly from younger patients, and lack of evidence for statin benefits in older patients has led to underutilization of statins in the elderly. The MIRACL study randomized 3,086 patients to 16 weeks of 80 mg/day of atorvastatin or placebo 24 to 96 hours after ACS and demonstrated significant decreases in the combined primary end point (nonfatal acute myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia). This post hoc analysis compared benefits of 80 mg of atorvastatin in older (=65 years) versus younger (<65 years) patients. Event rates were approximately two- to threefold higher in older than in younger patients. Treatment-by-age heterogeneity testing indicated no difference in treatment effect by age for any of the primary or secondary end points, and relative risk decreases in the primary end point with atorvastatin versus placebo were similar in younger and older patients (22% vs 14%, respectively). The safety profile of atorvastatin was similar between the 2 age groups. In conclusion, these results and a greater immediate cardiovascular risk in older patients argue for early, intensive atorvastatin therapy as routine practice after ACS. © 2007 Elsevier Inc. All rights reserved.
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