9,377 research outputs found
Folding and unfolding: interactions from geometry. INTERNATIONAL JOURNAL OF GEOMETRIC METHODS IN MODERN PHYSICS, vol. 9, n. 2, ISSN 0219-8878
No full textVitale Rosazza e l'esperienza del Grand Tour
No full textIl viaggio in Italia compiuto da Vitale Rosazza assieme alla moglie nell'estate del 1812 viene collocato nell'ambito delle più note descrizioni del Grand Tour, verificando ricorrenze e modalità di tale esperienza
Selective inhibition of cyclooxygenase (COX) isoenzymes and neuroinflammation
No full textMicroglia, the immune cells of the brain, are one of the key mediators of neuroinflammation.
Microglial activation leads these cells to produce various proinflammatory
and neurotoxic substances.
Several in vitro and in vivo studies have demonstrated that a decrease in the
levels of pro-inflammatory mediators in microglia can attenuate the severity of
neuro-degenerative diseases, including AD, PD, ALS, MS and Huntingtons
disease. Thus, regulation of excessive microglial activation should be of
therapeutic value especially in neuro-degenerative disorders.
Cyclooxygenase(COX) is a key enzyme in the conversion of arachidonic acid
into prostaglandins and other lipid mediators. It is widely accepted that this
enzyme play a pivotal role in the neuro-inflammatory process exacerbation. Two
COX isoforms are known: COX-1, constitutively expressed in most tissues,
classically considered as the isoform primarily responsible for maintaining the
homeostasis by mediating physiological responses, and COX-2, which
represents the inducible form, mainly activated in response to inflammatory
stimuli. In this respect, recent studies have also indicated a previously
unrecognized pro-inflammatory role of COX-1 in the pathophysiology of acute
and chronic neurological disorders. Consequently, it was reconsidered the
potential beneficial effect of COX-1 inhibition in the treatment of neuroinflammation
[1].
These findings prompted us to investigate the behaviour of two selective COX-1
inhibitors such as P6 (COX-1 IC50= 0.5 mM and COX-2 IC50 >100 mM) and P10
(COX-1 IC50= 0.09 mM and COX-2 IC50 = 2.49 mM) [2] in an in vitro experimental
model of inflammation, represented by mouse N13 microglial cells activated by
lipopolysaccharide (LPS) [3]. LPS is a component of the outer cell wall of gramnegative
bacteria and is well known as an inducer of inflammatory responses.
New selective COX-1 inhibitors are here proposed also as useful tools in
pharmacological studies to investigate the role of COX-1 isoenzyme in neuroinflammation
or more in general in all the investigations in which only COX-1
needs to be selectively inhibited.
The results of this study as well as their rationale will be presented and
discussed.
References:
1. Perrone, M.G.; Scilimati, A.; Simone, L., Vitale, P. Curr. Med. Chem.2010,17, 3769-805.
2. Di Nunno. L., Vitale, P., Scilimati, A., Tacconelli, S.; Patignani, P. J. Med. Chem. 2004, 47, 4881-90.
3. Calvello, R.; Panaro, M.A.; Carbone, M.L.; Cianciulli, A.; Perrone, M.G.; Vitale, P.; Malerba, P.; Scilimati,
A. Biochem. Pharmacol.,2011, submitted for publication
3-Aryl-2-isoxazolines and 3-arylisoxazoles from reaction of arylnitrile oxides and enolates: synthesis and reactivity
No full textIsoxazoles and isoxazolines are five-membered heterocycles widely used as versatile
building blocks in preparative organic chemistry, due to the easy cleavage of their N-O bond
[1]. They are masked forms of dicarbonyl compounds and are useful in the synthesis of other
heterocycles. Moreover, these heterocycles are components of a wide number of
pharmaceutical products and biologically active molecules [2], such as herbicides,
fungicides, analgesics, GABA-antagonists, anti-viral, antibacterial and anti-inflammatory
drugs [3].
The synthesis of functionalized 3-arylisoxazoles and 3-aryl-2-isoxazolines, from
reaction of arylnitrile oxides and enolates [4] will be reported in this presentation. The
regioselectivity and the synthetic versatility, due to the use of enolates intermediates, will be
discussed with particular attention to the methodologies useful for the preparation of
pharmacologically active heterocycles [5].
References
[1] (a) J. C. Badenock, "Topics in Heterocyclic Chemistry", Springer-Verlag Berlin Heidelberg, 2012, (G. W.
Gribble, ed.), vol 26, p. 261; (b) P. Grünanger, P. Vita-Finzi, J. E. Dowling, (eds.) Isoxazoles. Part 2, Vol. 170.
In: The Chemistry of Heterocyclic Compounds, John Wiley & Sons, 2009.
[2] (a) T. M. V. D. Pinho e Melo, Curr. Org. Chem. 2005, 9, 925; (b) P. Pevarello, R. Amici, M. G. Brasca, M.
Villa, M. Varasi Targets in Heterocyclic Systems 1999, 3, 301-339.
[3] J.J. Talley, D.L. Brown, J.S. Carter, M.J. Graneto, C.M. Koboldt, J.L. Masferrer, W.E. Perkins, R.S. Rogers,
A.F. Shaffer, Y.Y. Zhang, B.S. Zweifel, K. Seibert, J. Med. Chem. 2000, 43, 775.
[4] P. Vitale, A. Scilimati Curr. Org. Chem. 2013, 17, 1986-2000; (b) P. Vitale, A. Scilimati In: Advances in
Heterocyclic Chemistry, Eric F. V. Scriven and Christopher A. Ramsden (eds.) 2016, vol. 122, 1-41; (c) P.
Vitale, A. Scilimati, Synthesis (Germany) 2013, 45, 2940-2948.
[5] L. Di Nunno, P. Vitale, A. Scilimati, S. Tacconelli, and P. Patrignani, J. Med. Chem. 2004, 47, 4881; (b) P.
Vitale, S. Tacconelli, M. G. Perrone, P. Malerba, L. Simone, A. Scilimati, A. Lavecchia, M. Dovizio, E.
Marcantoni, A. Bruno, P. Patrignani J. Med. Chem. 2013, 56, 427
Special Issue: Proceedings of the Conference "Folding and Unfolding: Interactions from Geometry" Edited by G. Esposito, A. Messina, P. Vitale
No full textPreface to the proceedings of the conference
"Folding and unfolding: Interactions from geometry. Proceedings, Ischia, Italy, 8-12 June 2011
On the consistency of DSR models for multiparticle systems
No full textThe aim of the thesis is to provide a new original solution proposal to the infamous soccer-ball problem in the k-Poincaré inspired DSR (Doubly or Deformed Special Relativity) theory. More specifically, through the analysis of the kinematical properties of a composite system, we show that the single-particle deformation effects typical of the k-Poincaré setup should become weaker and weaker as the number of particles composing the system grows higher. After proposing a consistent definition of the "total" symmetry algebra of this system, we explore the so-called k-galilean limit of the theory. In particular, by avoiding the special relativistic no-interaction theorem, we are able to perform a first analysis of the quantum mechanical properties of an interacting two-particle system in the non-commutative k-Poincaré framework
The archaeoacoustics of San Vitale, Ravenna
No full textThis research tests and assesses whether sixth-century social and cultural dynamics can be archaeologically identified by including the study of acoustics in the context of extant Late Antique Christian architecture, namely the centrally planned domed octagonal church of San Vitale at Ravenna. Implementing a holistic archaeological research strategy that includes human sensory perception of acoustical phenomena is the best approach to unravelling the complexities of social and cultural mechanisms operating in the sixth-century Mediterranean basin. The methods and issues of Archaeoacoustics are critiqued and developed in order to comment on the intentionality of acoustic attributes in sixth-century ecclesiastical architecture.The space syntax of San Vitale has been considered for isovists at key locations during the liturgical procession and sequence of the Mass celebration. These are compared with mapped areas of perceiving the acoustic characteristics of Clarity and Reverberation Time. Combining the visual and acoustic analysis of San Vitale, with a better understanding of its date and construction phases, the physical geometry and temporal logic of the church are discussed in relation to the reflexive exchange of influence between Ravenna, Milan and Constantinople. It is posited that liturgical and musical time and tempo is materially expressed in the evident and conceptual substance of San Vitale, a suggestion that offers a springboard for future study and debate
Is unilateral antegrade cerebral perfusion equivalent to bilateral cerebral perfusion for patients undergoing aortic arch surgery?
No full textA best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether unilateral antegrade cerebral perfusion is equivalent to bilateral cerebral plegia for cerebral protection during aortic arch surgery. Altogether 233 papers were found using the reported search, of which 17 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. These papers documented antegrade selective cerebral perfusion in a total of 3548 patients: bilateral cerebral perfusion in 2949 patients and unilateral perfusion in 599 patients. Both methods of cerebral perfusion resulted in neurological injury rates of <5%, but the period of antegrade cerebral perfusion allowed by bilateral perfusion was significantly higher. While unilateral perfusion allowed around 30-50 min, bilateral perfusion allowed 86 to over 164 min of ASCP with an acceptably low CVA rate. Therefore, we conclude that while both methods are acceptable, once the ASCP time is expected to rise over 40-50 min, bilateral cerebral perfusion is the technique that is best documented to be safe
Vertical gradient of regional lung inflation in adult respiratory distress syndrome
No full textWe obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at zero cm H2O end-expiratory pressure. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no. 1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density x height. The total volume of the basal CT section was 49 +/- 2.5 ml x m-2 (mean +/- SE) in control subjects and 43 +/- 2.3 ml x m-2 in patients with ARDS (p = not significant [NS]). The tissue volume, however, was 16.7 +/- 0.8 ml x m-2 in control subjects and 31.6 +/- 1.7 ml x m-2 in patients with ARDS (p < 0.01). The g/t ratio in level 1 averaged 4.7 +/- 0.5 in control subjects and 1.2 +/- 0.2 in patients with ARDS (p < 0.01), and this ratio decreased exponentially from level 1 to level 10, both in controls and patients with ARDS. The Kd constant of the exponential decrease was 13.9 +/- 1.3 cm in control subjects and 7.8 +/- 0.8 cm in patients with ARDS (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS
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