177,756 research outputs found
Estrogen, cognition and female ageing
No full textStarting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of β-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged ≥65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed. © 2007 Oxford University Press
Generalized Schrodinger-Poisson type systems
No full textIn this paper we study the boundary value problem
\left\{
\begin{array}{ll}
-\Delta u+ \eps q\Phi f(u)=\eta|u|^{p-1}u & \text{in } \Omega, \\
- \Delta \Phi=2 qF(u)& \text{in } \Omega, \\
u=\Phi=0 & \text{on }\partial \Omega,
\end{array}
\right. where is a smooth bounded
domain, , is a
continuous function and is the primitive of such that
We provide existence and multiplicity results assuming on
a subcritical growth condition. The critical case is also
considered and existence and nonexistence results are proved
beta-Lithiation of Oxazolinyloxirane: Synthetic Utility
No full textβ-Lithiated oxazolinyloxirane 13a, generated by deprotonation of (R*, R*) trisubstituted oxazolinyloxirane 12a with s(-BuLi/TMEDA in Et2O at -100 °C, was found to be chemically and configurationally stable for at least 1 h at this temperature and reacted stereospecifically with electrophiles to give the corresponding tetrasubstituted derivatives 14a-j with complete retention of configuration at the β-carbon
Synthesis of Sulfoximines and Sulfonimidamides Using Hypervalent Iodine Mediated NH Transfer
No full textThe development of NH transfer reactions using hypervalent iodine and simple sources of ammonia has facilitated the synthesis of sulfoximines and sulfonimidamides for applications across the chemical sciences. Perhaps most notably, the methods have been widely applied in medicinal chemistry and in the preparation of biologically active compounds, including in the large-scale preparation of an API intermediate. This review provides an overview of the development of these synthetic methods involving an intermediate iodonitrene since our initial report in 2016 on the conversion of sulfoxides into sulfoximines. This review covers the NH transfer to sulfoxides and sulfinamides, and the simultaneous NH/O transfer to sulfides and sulfenamides to form sulfoximines and sulfonimidamides, respectively. The mechanism of the reactions and the identification of key intermediates are discussed. Developments in the choice of reagents, and in the reaction conditions and setups used are described
Regio- and Stereoselective Lithiation of 2,3- Diphenylaziridines: A Multinuclear NMR Investigation
No full textThe R-lithiation-trapping sequence of trans-N-alkyl-2,3-diphenylaziridines (s-BuLi or s-BuLi/TMEDA),
taking place with a stereochemistry which dramatically depends on the solvent coordinating ability (inversion of configuration in THF and retention in toluene), has been carefully investigated. 1H,13C, and 7Li multinuclear NMR investigations at low temperature suggest that two differently configured lithiated aziridines (monomeric is-1-Li in THF and dimeric trans-1-Li in toluene) are involved
Nitrogen Dynamics and Reactivity of Chiral Aziridines: Generation of Configurationally Stable Aziridinyllithiums
No full textDiastereomeric oxazolinylaziridines (R, R)-9 and (R, S)-9 have been regioselectively lithiated at the aposition with respect to the oxazolinyl ring. The resulting aziridinyllithium compounds proved to be chemically and configurationally stable under the experimental conditions used, thus furnishing, upon trapping with electrophiles, chiral 2,2-disubstituted aziridines, in contrast to the corresponding alpha-lithiated oxazolinyloxiranes that have been reported to be chemically stable but configurationally unstable. This peculiar behavior of the nitrogen-bearing heterocycle has been rationalized on the basis of DFT calculations and the observed dynamics of the aziridine nitrogen atom. The DFT analysis allowed the disclosure of a solvent-dependent differing stability of diastereomeric lithiated aziridines (R, R)-9-Li and (R, S)-9-Li, suggesting eta(3)-coordinated oxazolinylaziridinyllithium compounds as likely intermediates. Such intermediates could be the result of a dynamically controlled lithiation that relies on the preliminary formation of a complex between the lithiating agent and the oxazolinyl ring. According to this model, the competing complexation of the lithiating agent by the lone pair of electrons on the aziridine nitrogen would cause addition to the oxazoline C=N bond, thus ending up with the formation of oxazolidines, which are precursors of useful chiral ketoaziridines. The proposed model has been also supported by estimating the nitrogen inversion barrier by dynamic NMR spectroscopic experiments
Flow Technology for the Genesis and Use of (Highly) Reactive Organometallic Reagents
No full textIn the field of organic synthesis, the advent of flow chemistry and flow microreactor technology represented a tremendous novelty in the way of thinking and performing chemical reactions, opening the doors to poorly explored or even impossible transformations using batch methods. In this Concept article, we would like to highlight the impact of flow chemistry for exploiting highly reactive organometallic reagents, and how, alongside the well-known advantages concerning safety, scalability, and productivity, flow chemistry makes possible processes that are impossible to control by using the traditional batch approach
Evaluation of left ventricular systolic function during atrial fibrillation: Is it reliable?
No full textFor adequate treatment of patients with atrial fibrillation (AF) clinicians need information on left ventricular (LV) systolic function. This is generally evaluated using echocardiography to calculate LV ejection fraction (LV-EF) or global longitudinal strain (GLS), which can detect early systolic abnormalities when LV-EF is still normal. In using both LV-EF and GLS the key point is that measures should be reliable and reproducible, regardless of cardiac rhythm. Unfortunately, many clinicians question the reliability of the echocardiographic measures during AF because of several reasons. First, AF patients are often excluded in echocardiographic studies, thus data for the validity of systolic function indices during AF are limited [ 1 ]. Second, the prognostic value of cardiac function parameters may be affected by AF [ 2 ]. Third, methods to improve assessment of LV function during AF are rarely applied in echocardiographic practice because they are generally cumbersome and time-consuming, and many echocardiographers just rely on eye-ball evaluations. Thus, assessment of cardiac function in patients with AF is problematic
The renaissance of strained 1-azabicyclo[1.1.0]butanes as useful reagents for the synthesis of functionalized azetidines
No full textSince their discovery in the late 1960s, 1-azabicyclo[1.1.0]butanes have demonstrated to be interesting precursors of azetidines, because of the peculiar reactivity of the C3-N bond that allows double functionalization in the 1,3 positions. In particular, the recent advances reported by Baran, Lopchuk, Aggarwal, and others witness the synthetic relevance of such strained azabicycles in the synthesis of highly functionalized azetidines. However, the synthesis and reactivity of 1-azabicyclo[1.1.0]butanes remains a poorly explored topic in organic chemistry. This review aims to furnish a comprehensive knowledge on the preparation of 1-azabicyclo[1.1.0]butanes and the transformation into functionalized saturated four-membered azacycles
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