Search results for "Azetidine"
showing 10 items of 33 documents
Arabidopsis thaliana nicotianamine synthase 4 is required for proper response to iron deficiency and to cadmium exposure.
2013
International audience; The nicotianamine synthase (NAS) enzymes catalyze the formation of nicotianamine (NA), a non-proteinogenic amino acid involved in iron homeostasis. We undertook the functional characterization of AtNAS4, the fourth member of the Arabidopsis thaliana NAS gene family. A mutant carrying a T-DNA insertion in AtNAS4 (atnas4), as well as lines overexpressing AtNAS4 both in the atnas4 and the wild-type genetic backgrounds, were used to decipher the role of AtNAS4 in NA synthesis, iron homeostasis and the plant response to iron deficiency or cadmium supply. We showed that AtNAS4 is an important source for NA. Whereas atnas4 had normal growth in iron-sufficient medium, it dis…
IMPROVE-IT: what have we learned?
2016
Purpose of review: Recent studies and dyslipidemia treatment guidelines indicate that combination lipid-lowering therapy is frequently needed and its use has increased in recent years. Ezetimibe and simvastatin as a fixed dose is an efficacious treatment choice based on positive results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). In this review, we discuss recent controversies surrounding ezetimibe and provide clinical perspective on the results of the IMPROVE-IT study. Recent findings: IMPROVE-IT is the first trial that demonstrates a significant clinical benefit of a nonstatin hypolipidemic agent (ezetimibe) used in combination with sta…
Ezetimibe/Simvastatin 10/20 mg versus Rosuvastatin 10 mg in high-risk hypercholesterolemic patients stratified by prior statin treatment potency
2010
Abstract Objective This post-hoc analysis compared the lipid-altering efficacy of Ezetimibe/Simvastatin 10/20 mg (EZ/Simva) versus Rosuvastatin 10 mg (Rosuva) in patients stratified by statin potency/dose prior to randomization. Methods Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite prior statin treatment (n = 618) were randomized 1:1 to EZ/Simva 10/20 mg or Rosuva 10 mg for 6 weeks. Percent change from baseline in lipids and attainment of lipid targets were assessed within each subgroup (low potency n = 369, high potency n = 249). Consistency of the treatment effect across subgroups was evaluated by testing for treatment-by-subgroup interaction. No multiplicity …
Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately c…
2009
SUMMARY Aims: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe ⁄simvastatin (EZE ⁄SIMVA) 10 ⁄20 mg vs. rosuvastatin (ROSUVA) 10 mg. Methods: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) ‡ 2.59 and £ 4.92 mmol ⁄l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for ‡ 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation ⁄screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose ⁄potency, patien…
Ezetimibe alone or in combination with simvastatin increases small, dense low-density lipoproteins in healthy men: a randomized trial
2010
Aims The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution. Methods and results A single-centre, randomized, parallel three-group open-label study was performed in 72 healthy men with a baseline LDL-cholesterol (LDL-C) concentration of 111 ± 30 mg/dL (2.9 ± 0.8 mmol/L). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24), or their combination ( n = …
Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.
1997
Abstract In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 μM tADA ( ec 50: 1.2 μM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity. © 1997 Elsevier Science Ltd. All rights reserved.
The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions
2000
The present experiments were designed to extend previous work showing that acute intermittent (-)nicotine treatment upregulates the level of fibroblast growth factor-2 (FGF2) mRNA in several rat brain regions, by the use of the nicotinic acetylcholine receptor (nAChR) agonist ABT-594 with preferential selectivity for the alpha4beta2 nAChR subtype. ABT594 treatment led to a well-defined temporal and regional upregulation of FGF-2 mRNA. A double labelling analysis showed that the up-regulation of FGF-2 mRNA involves both neuronal and non-neuronal cells. The effects of ABT-594 on FGF-2 expression were antagonized by the preferential alpha4beta2 antagonist dihydrobetaerythroidine (DHbetaE), but…
Ring splitting of azetidin-2-ones via radical anions
2012
The radical anions of azetidin-2-ones, generated by UV-irradiation in the presence of triethylamine, undergo ring-splitting via N-C4 or C3-C4 bond breaking, leading to open-chain amides. This reactivity diverges from that found for the neutral excited states, which is characterised by alpha-cleavage. The preference for beta-cleavage is supported by DFT theoretical calculations on the energy barriers associated with the involved transition states. Thus, injection of one electron into the azetidin-2-one moiety constitutes a complementary activation strategy which may be exploited to produce new chemistry.
Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair
2021
Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocyc…
Stereocontrolled synthesis of azeto[2,1-b] quinazolines bearing three stereocenters via the intramolecular [2+2] cycloaddition between ketenimines an…
2004
Abstract A highly stereoselective synthesis of azeto[2,1- b ]quinazolines bearing three stereocenters (C1, C2, and C8) has been achieved via intramolecular [2+2] cycloaddition between ketenimine and imine functions supported on an ortho -benzylic scaffold. An asymmetric center adjacent to the iminic nitrogen atom, the future C8 carbon of the bicyclic product, efficiently controls the absolute configuration of the two new stereogenic carbon atoms of the azetidine ring, C1 and C2.