23 research outputs found

    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    Electron and Energy Transfer in Supramolecular Complexes Designed for Artificial Photosynthesis. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 631. 50 pp. Uppsala. ISBN 91-554-5

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    In the society of today the need for alternative energy sources is increasing. The construction of artificial devices for the conversion of sunlight into electricity or fuel seems very attractive from an environmental point of view, since these devices are based on processes that does not necessarily generate any harmful biproducts. In the oxygen evolving photosynthetic process highly efficient energy and electron transfer reactions are responsible for the conversion of the sunlight into chemically stored energy and if the same principles can be used in an artificial device, the only electron supply required, is water. This thesis describes energy and electron transfer reactions in supramolecular complexes where the reactions are intended to mimic the basic steps in the photosynthetic process. All complexes are based on ruthenium(II)-trisbipyridine as photosensitizer, that is covalently linked to electron donors or electron or energy acceptors. The photochemical reactions were studied with time resolved transient absorption and emission measurements. In the complexes that mimic the donor side of Photosystem II, where a manganese cluster together with tyrosine catalyses the oxidation of water, intramolecular electron transfer was found to occur from Mn(II) or tyrosine to photo-oxidized Ru(III). Studies of a series of Ru(II)-Mn(II) complexes gave information of the quenching of the Ru(II) excited state by the coordinated Mn(II), which is important for the development of multi-nuclear Ru(II)-Mn complexes. In the supramolecular triad, PTZ-Ru 2+ -Q, the charge separated state, PTZ +• -Ru 2+ -Q −• , was rapidly formed, and further development where a second electron acceptor is linked to quinone is planned. Ultra fast energy transfer (τ<200 fs), was obtained between ruthenium(II) and osmium(II) in a small artificial antenna fragment. Fast and efficient energy transfer is important in larger antennas or photonic wires where a rapid energy transfer is desired over a large distance

    Excited-State Properties of Heteroleptic Iridium(III) Complexes Bearing Aromatic Hydrocarbons with Extended Cores

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    International audienceThe synthesis, complete structural characterization, electrochemistry, and excited-state dynamics of a series of four bis-heteroleptic iridium(III) charge-transfer complexes composed of a single acac-functionalized and two ortho-metalated 2-phenylpyridine ligands. The formed iodophenyl complex (2) was used as a metallosynthon to introduce extended-core ethynyltolyl (3), ethynylpyrene (4), and ethynylperylene (5) residues into these structures projecting from the acac ancillary ligand. Static and dynamic photoluminescence along with ultrafast and conventional transient absorption measurements in conjunction with cyclic voltammetry were employed to elucidate the nature of the intramolecular energy-transfer processes occurring in the excited states of polychromophores 4 and 5 and are directly compared with those of model complexes 2 and 3. Upon charge-transfer excitation of these molecules, the long-lived triplet-state metal-to-ligand charge-transfer ((3)MLCT)-based photoluminescence readily observed in 2 and 3 (τ = 1 μs) is nearly quantitatively quenched, resulting from production of the associated triplet intraligand ((3)IL) excited states in 4 and 5 through intramolecular triplet-triplet energy transfer. The respective formation of the extended-core (3)*pyrenyl and (3)*perylenyl-localized excited states in 4 and 5 is confirmed by their ultrafast excited-state evolution, which ultimately generates features associated with these (3)IL excited states and their greatly extended excited-state lifetimes with respect to the parent complexes 2 and 3

    Bioinorganic photochemistry : frontiers and mechanisms

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    Nanoparticles in dendrimers: From synthesis to application

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