67,875 research outputs found
«Simmetrie sarcastiche». Esili e migrazioni nella letteratura contemporanea di lingua tedesca degli scrittori di origine romena (C.D.Florescu e C.-F.Banciu)
No full text
Design and synthesis of new [4,5-b] and [4,5-c] imidazopyridines as potential fluorophores/inhibitors for Human Cyclooxygenase-1.
No full textIn recent years, a great deal of research effort has been devoted to identifying targeted fluorophores, for intraoperative detection of neoplastic bodies and real-time assessment of tumor borders to achieve complete tumor removal [1].
The aim of this work is to design, synthesize new aryl derivatives of [4,5-b] and [4,5-c] imidazopyridines as potential ligand/inhibitors of Cyclooxygenase-1, isoform definitively ascertained as a tumor-associated target in ovarian cancer.
In this regard, it was possible to carry out a Structure-based virtual screening (SBVS) performed with the Fingerprints for Ligands and Proteins (FLAP) software, by taking advantage of the recently published crystallographic structure of human Cyclooxygenase-1 (hCOX1) [2]. In this preliminary step, we designed
different imidazopyridine derivates, substituted on both the imidazole ring and the aromatic ring, as can be seen from Figure 1. Then, identified the pocket of hCOX1, it was possible to calculate binding poses of our compounds and differentiate highly active structures from less active or inactive structures. Based on the results of the SBVS, we select the most promising candidates for the synthetic phase: the strategy adopted involves the direct condensation between different benzaldehydes, previously treated with Na2S2O5, and the appropriate diaminopyridine. The products obtained were isolated, purified and characterized by NMR Spectroscopy and Mass Spectrometry.
The synthesized compounds were finally tested to evaluate their binding/inhibitory activity and selectivity towards COX-1 enzyme
Innovazione tecnologica e stabilità finanziaria
No full textInnovazione tecnologica e stabilità finanziari
Synthesis and biological evaluation of 3-alkyloxazolidin-2-ones as reversible MAO inhibitors.
No full textThe discovery of the two forms of MAO had led to significant advances in the understanding of
the physiological and biochemical roles that these enzymes play in normal processes and in
disease states. The recent development of a new generation of highly selective reversible MAO
inhibitors (MAOIs) have led to a renewed interest in the therapeutic potential of these new
compounds with respect to early irreversible MAOIs. In fact, reversible MAOIs offer new hopes
for generating superior anti-depressant and anti-parkinsonian agents by virtue of the selective
inhibition of MAO-A and MAO-B, respectively. Aryloxazolidinones are one of the relatively
new classes of MAOIs. Their “lead compound” is Toloxatone (Humoryl®), the first reversible
and selective MAO-A inhibitor introduced in clinical practice as an anti-depressant. In order to
investigate the importance and hence the biological role played by the anisyl (p-methoxyphenyl)
group linked to N 3 atom of Toloxatone oxazolidinone ring or more in general of an aromatic
group, some new N 3 -alkyloxazolidinones were synthesized and their ability to inhibit MAO-A
and MAO-B enzymes was evaluated by a fluorimetric method that uses the kynuramine as
substrate. Also modifications at C 5 of the 2-oxazolidinone ring were considered. The set of N 3 -
alkyl substituted and at C 5 modified compounds showed ability to inhibit MAO-A and MAO-B
but with lower extent than Toloxatone used as reference drug. Such biological results provide
insights into structure-activity relationships, confirming that is necessary the presence of N 3 -aryl
moiety to act as a potent reversible MAO inhibitor, not possible in the same extent when the aryl
is replaced by an alkyl group (Ki≈ 10 -7 M versus 10 -3 –10 -4 M)
Role of the serotonin receptor 7 in brain plasticity: From development to disease
No full textOur knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology have advanced considerably in recent years. A wealth of data show that 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows the rescue of long-term potentiation (LTP) and long-term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, modulates the function of immune cells, and is likely to play a role in the gut-brain axis. In this review, we will mainly focus on recent findings on this receptor's role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gastrointestinal (GI) tract and immune system
Free radicals and brain damage in newborns with hypoxic-ischemic lesion
No full textFree radicals (FR) are highly reactive chemical molecules containing one or more unpaired electrons. Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), are normally produced in living organisms. When over produced, they are major mediators of cell and tissue injury. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress in vivo is a degenerative process due to the over production and propagation of FR reactions. FR reactions lead to oxidation of lipids, proteins, polysaccharides and to DNA damage. Newborns and particularly preterm infants are very susceptible to FR oxidative damage. In these subjects, there is evidence of an imbalance between antioxidant and oxidant-generating systems enhancing oxidant injury
PM2.5 and PM10 oxidative potential at a Central Mediterranean Site: Contrasts between dithiothreitol- and ascorbic acid-measured values in relation with particle size and chemical composition
No full textIn this study, PM2.5 airborne particulate matter was collected over a full year at a costal site of the Central Mediterranean Sea and analysed for its chemical composition and oxidative potential (OP), determined by the dithiothreitol (DTT) and the ascorbic acid (AA) assays. In autumn-winter, the volume normalized oxidative OP (OPV) were 0.29 ± 0.03 nmol min−1 m−3 and 0.21 ± 0.03 nmol min−1 m−3 for the DTT (OPDTTV) and AA (OPAAV) assay, respectively. In spring-summer the OPDTTV values were higher than OPAAV responses, i.e., 0.19 ± 0.02 nmol min−1 m−3 vs. 0.09 ± 0.01 nmol min−1 m−3. Overall, marked seasonality was observed with higher values in Autumn-Winter (AW) than in Spring-Summer (SS), i.e., 1.5 and 2.3 times increase for OPDTTV and OPAAV, respectively. In the cold season, the OPV activity was broadly correlated with metals and carbon species, such as K+, NO3−, Ba, Cd, Cu, Fe, Mn, P, V, OC, EC, Acetate, Oxalate and Glycolate (p < 0.05). This suggested the main contribution of a “mixed anthropogenic” source, consisting of the biomass burning (K+, OC and EC) and traffic (Ba, Cu, Fe, Mn, V, EC) emissions. In SS, OPV was significantly correlated with only few species i.e., OC, EC, Cu, and NO3−, suggesting main association with the “mixed anthropogenic” and the “reacted dust” sources. For each sampling day, PM2.5 and PM10 samples were simultaneously collected and analysed to investigate the variation of the OP activity in relation with the particle size and chemical composition. OPDTTV values exhibited a poor particle-size dependence, with similar values close to 0.20 ± 0.04 nmol min−1 m−3 in both fractions. This could be explained by the association of OPDTTV with species mainly accumulated in the fine fraction, i.e., OC, POC and EC and K+. Otherwise, the OPAAV responses exhibited a clear particle-size dependence, with significantly higher values for PM10 than for PM2.5, i.e., 0.35 ± 0.06 vs. 0.21 ± 0.03 nmol min−1 m−3 in AW and 0.23 ± 0.04 vs. 0.09 ± 0.01 in SS. This may be supported by the strong correlation of OPAAV with Cu and Fe, which were most abundant metals in the PM10 fraction. The data of specific monitoring days were investigated in detail to better highlight the impact of some individual redox active species on the OPDTTV and OPAAV responses.The oxidative potential of PM2.5 and PM10 samples was assessed with Dithiothreitol and Ascorbic Acid assays: the variation of OP responses was related with the PM size and chemical composition
Performance Analysis of a Noncontact Plastic Fiber Optical Fiber Displacement Sensor with Compensation of Target Reflectivity
No full textAn inexpensive fiber-based noncontact distance sensor specific for monitoring short-range displacements in micromachining applications is presented. To keep the overall costs low, the sensor uses plastic optical fibers and an intensiometric approach based on the received light intensity after the reflection from the target whose displacement has to be measured. A suitable target reflectivity compensation technique is implemented to mitigate the effects due to target surface nonuniformity or ageing.The performances of the sensor are first evaluated for different fiber configurations and target reflectivity profiles and positions using a numerical method based on Monte Carlo simulations. Then, experimental validations on a configuration designed to work up to 1.5mm have been conducted. The results have confirmed the validity of the proposed sensor architecture, which demonstrated excellent compensation capabilities, with errors below 0.04mm in the (0-1)mm range regardless the color and misalignment of the target
Exceptional singularities of codimension one holomorphic foliations
No full textWe study some numerical properties of singularities of codimension one holomorphic foliations which can be analytically collapsed to one point. Some local and global dynamical consequences are deduced
- …
