1,721,029 research outputs found
Le conoscenze sul dolore degli studenti del corso di laurea in Infermieristica : studio trasversale
No full textPremessa: La tematica del dolore viene affrontata sin dall’ambito formativo di base; nonostante ciò, è noto in letteratura (1, 3-4) che gli infermieri presentano carenti conoscenze e tendono a sottostimare tale problema. Appare utile, come suggerito da alcuni autori, indagare le conoscenze in materia già durante la formazione.
Scopo: Indagare le conoscenze dei futuri infermieri nell’ambito del dolore, presso l’Università degli Studi di Milano.
Materiali e metodi: Studio trasversale condotto tramite l’utilizzo di un questionario validato per il contesto italiano, Italian Nurses’ Knowledge and Attitudes Survey Regarding Pain (35), inviato alla mailing list UniMI degli iscritti al 2° e 3° anno del corso di laurea in Infermieristica attraverso un link SurveyMonkey.
Risultati: Sono state inviate 1137 e-mail; 208 studenti hanno compilato il questionario. L’utilizzo del placebo, l’influenza del dolore sui parametri vitali e sul sonno risultano concetti ancora poco chiari; dal confronto con la letteratura, tuttavia, emerge che le conoscenze degli studenti non si discostano di molto da quelle dei professionisti.
Conclusioni: Lo studio supporta l’ipotesi, presente in letteratura, che la carenza di conoscenze in alcuni ambiti del dolore possa essere affrontata già nella formazione triennale. Sarebbero utili studi su più larga scala, per vedere se i risultati siano confermati e in tal caso consolidare le conoscenze in merito ad alcuni aspetti del problema
Synthesis and molecular dynamic simulations of a Vi antigen sulfated analogue
No full textVi capsular polysaccharide (Vi antigen) was first identified as the virulence factor of Salmonella enterica serovar typhi, the causative agent of typhoid fever in humans. It is a linear homopolymer made up of alpha-(1→4)-linked N-acetyl galactosaminuronic acid with a 60-70% O-acetylation at C-3. This antigen is highly immunogenic and has been used for the formulation of one of the currently available vaccines against typhoid.1 In the context of vaccine development, the search for carbohydrate analogues is stimulated by the intrinsic instability of several polysaccharide vaccines from natural sources or by the need to understand/control the immunological events under analysis.
We are interested in the preparation of oligomeric sulfated analogues of Vi antigen, i.e. analogues in which the 6-carboxylic group has been substituted with a sulfate, to study the influence of the sulfo pH-independent ionizable group on the biological activity. The modification from galacturonic to 6-O-sulfogalactose does not actually generate an isosteric analogue, but in principle should not significantly interfere with the immunostimulating activity of Vi antigen. Indeed, it has been demonstrated that the immunogenicity of Vi is strongly related to the content of O-acetyl groups and not to the presence of the carboxyl group.2 In fact, the acetate groups confer the hydrophobic properties to the molecular surface and dominate the surface of the polysaccharide, probably shielding the carboxyls from interaction with other molecules, even if only partial 3-O-acetylation seems necessary to maintain the flexibility of the molecules.3 So, the modification of position 6 should not influence the biological activity provided that the conformational properties at the alpha-(1→4) glycosidic linkage, as well as the overall geometry of the polymer, are maintained.
Herein we will report the conformational analysis and a stereoselective synthesis of a Vi antigen sulfated-analogue dimeric fragment
Implementing the Floods Directive: a procedure for flood risk analysis and mapping
No full textThe European “Floods” Directive (Directive 2007/60/EU) asks Member States to develop Flood Risk Management Plans (FRMPs) by 2015. These plans must be based on flood hazard maps and flood risk maps and should address all aspects of flood risk management, taking into account costs and benefits of proposed mitigation tools. This paper presents a methodology to carry out flood risk analyses which support the development of flood risk maps, as required by the Floods Directive. According to the latter, the procedure was designed to be implemented at the catchment scale; the River Mallero Basin (in north Italy) was used as test-area.
The procedure presents three main peculiarities. First is its feasibility for the whole Italian territory as data required as inputs have been identified among those which are available for all Italian river basins. Second is the possibility to express risk in monetary terms (i.e. expected damage), at least for those categories of damage for which suitable models are available. This is an important aspects when costs/benefits analysis must be carried out. Last but not least is flexibility. The procedure is organised in independent modules; each module allows the estimation of a certain type of damage (i.e. direct, indirect, intangibles) on a certain sector (e.g. residential, industrial, agriculture, environment, etc.). Thus, analysts can decide to omit the estimation of non significant damages by simply not implementing respective modules; on the other hand, each module can be modified without affecting the whole procedure. This way risk analysis/maps can be continuously updated/improved as required by the same Floods Directive
A 2,3-carbamate-bearing allyl galactosamine donor for the synthesis of repeating alfa-(1 4)-linked galactosamine units
No full textThe 1,2-cis-linked 2-amino-2-deoxy sugar structure is found in various oligosaccharides of biological importance. The repeating GalpNAc--(1→4)-GalpNAc unit constitutes for example an essential motif incorporated in a range of oligosaccharides, e.g. the repeating unit of the O-antigen moiety of the lipopolysaccharide from Escherichia Coli O142 or Sphaerotilus natans.[1] Vi antigen is instead a linear homopolymer of -(1→4)-linked N-acetyl galactosaminuronic monomers, with a variable degree of O-acetylation at the C3 position. Vi antigen is a capsular polysaccharide found mainly in Salmonella typhi and Salmonella paratyphi C, two serotypes of Salmonella that are responsible for severe infection in humans.[2]
Although in the past years there has been much progress in carbohydrate chemistry, 1,2-cis-selective glycosylation of gluco- or galactosamines is still a challenge. 2-Azidoglycosyl donors, developed many years ago, are still employed for the synthesis of 2-amino-2-deoxy -glycosides, even if glycosylations suffer of low selectivity. Progress in resolving these issues has been made with the development of donors carrying a 2,3-trans-carbamate group, which has attracted much attention as a stereodirecting protection in glycosylation reactions. The fused carbamate ring proved to be a non-participating group and favors the formation of -glycosides. So far, different studies have demonstrated that 2,3-oxazolidinone protected thioglycosides are highly efficient substrates for the synthesis of -linked glycosides.[3]
Herein we report a new 2,3-oxazolidinone protected galactosamine donor, bearing an allyl group at the anomeric position. The allyl group, in addition to its traditional role as a valuable anomeric protecting group, can also be converted into a good leaving group for glycosylation. Thus, the allyl glycoside is first isomerized to the corresponding prop-1-enyl glycoside, which, after chemoselective activation of the anomeric enol ether moiety with a suitable electrophile in the presence of the glycosyl acceptor, leads to the formation of the disaccharide product.[4] This method has the advantage that prop-1-enyl glycoside can be directly derived from allyl glycoside with a variety of facile and highly effective isomerization methods and immediately subjected to glycosylation.
Herein we describe the synthesis of a galactosamine building block, which has the anomeric position protected by an allyl group, and positions 2 and 3 involved in the formation of an oxazolidinone ring. The proper donor and acceptor to perform a -(1→4) glycosylation have been obtained from this common building block. The new 2,3-oxazolidinone protected allyl galactosamine donor has been subjected to glycosylation reactions to study its reactivity and the stereoselectivity of the process.
1. a) Landersjö, C.; Widmalm, G. Biopolymers 2002, 64,283; b) Takeda, M.; Nakamori, T.; Hatta, M.; Yamada, H.; Koizumi,
J.I. Int. J. Biol. Macromol. 2003, 33, 245
2. a) Daniels, E.M.; Schneerson, R.; Egan, W.M.; Szu, S.C.; Robbins, J.B. Infect. Immun. 1989, 57, 31592; b) Heyns, K.;
Kiessling, G. Carbohydr. Res. 1967, 3, 340
3. See for examples: a) Kerns R.J., Zha C., Benakli K.,. Liang Y.Z, Tetrahedron Lett. 2003, 44, 8069; b) Olsson, J. D. M.;
Eriksson, L.; Lahmann, M.; Oscarson, S. J. Org. Chem: 2008, 73, 7181; c) Yang, L.; Ye, X-S. Carbohydr. Res. 2010, 345,
1713; d) Yang, L.; Zhu, J. ; Zheng, X-J. ; Tai, G. ; Ye, X-S. Chem. Eur. J. 2011, 17, 14518
4. Wang, Y.; Zhang, X.; Wang, P. Org. Biomol. Chem. 2010, 8, 4322 and references herein reported.
We acknowledge MIUR-Italy (PRIN 2008) for financial support
A full conformational characterization of 13-ethylprogestogens through theoretical calculations and nuclear magnetic resonance spectroscopy
No full textThe conformational preference of a group of 13-ethylsteoids and related estranes have been determined through theoretical calculations at B3LYp/6-31G level in order to ascertain differences and similarities in conformational behavior which might, in principle, influence the activity. Attention was focussed on two geometrical features usually related to the progestional activity of this class of compounds, namely, the inversion of the A ring and the orientation of the 13-ethyl group. The present calculations show that the absence of the C10 methyl group, like in levonorgestrel, 3-ketodesogestrel, and gestodene, makes the inversion of the A ring easier than in norethisterone andethisterone even if in any case the 1alpha,2beta-half-chair conformation remains preferred. The presence of ethyl group for the trans orientation is maintened by all the 13-ethylprogestogens though in gestodene also the g+ gauche conformation is significantly populated. This preference was experimentally supported through a high field NMR spetroscopy study of the ethylsteroid
The capsular polysaccharide Vi from Salmonella typhi: synthesis and molecular dynamic simulations of short analogue fragments
No full textVi capsular polysaccharide (Vi antigen) is the virulence factor of Salmonella enterica serovar typhi, the causative agent of typhoid fever in humans. It is a linear homopolymer made up of alpha-(1→4)-linked N-acetyl galactosaminuronic acid with a 60-70% O-acetylation at C-3. Vaccination with purified Vi antigen from Salmonella typhi can protect against typhoid fever, although many aspects of the mechanism of action have yet to be established. It has been demonstrated that the immunogenicity of Vi is strongly related to the content of O-acetyl groups and seems not related to the presence of the carboxyl groups. In fact, the acetate groups dominate the molecular surface of the polysaccharide and confer hydrophobic properties to it, probably shielding the carboxylic groups from interaction with other molecules, even if only partial 3-O-acetylation seems necessary to maintain the flexibility of the molecules. Being interested in the study of the role of the negative charge of the Vi biopolymer on the biological activity, we have planned the preparation of analogues where the carboxylic group has been substituted with a pH-independent ionizable group, i.e. the sulfate group. The sulfate group has been selected after preliminary investigations through molecular dynamics simulations on a hexasaccharide Vi antigen fragment, that showed similarities between the conformational behavior of the natural antigen and the sulfate analogue, where the galacturonic residues have been replaced with 6-O-sulfo-galactoses.
Herein we will report our results on the conformational analysis and the stereoselective synthesis of Vi antigen sulfated-analogue fragments
Complete 1H and 13C assignments of (21R) and (21S) diastereomers of argatroban
No full textThe complete 1H and 13C NMR assignments are reported for the antithrombotic (21R)- and (21S)-argatroban by 1D and 2D NMR experiments (HSQC, HMBC, NOESY and 1H--1H COSY). Some well-resolved signals could be used for an accurate measurement of the diastereomeric composition of argatroban. Copyright (c) 2007 John Wiley & Sons, Ltd
New anionic glycoglicerolipids targeting protein kinase B (Akt)
No full textProtein kinases are enzymes involved in the regulation of many crucial cellular processes like proliferation, differentiation and apoptosis. Among them, the serine/threonine protein kinase B (PKB), also known as Akt, plays a key role as a component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis, which is implicated in aberrant tumor cell signaling. Inappropriate activation of the Akt kinase is a common event in human tumors and Akt is a critical player in cell survival. Thus, inhibitors that target PI3Ks and its downstream effectors, including PKB are potentially relevant for cancer therapy. PI3K activation generates 3-phosphorylated phosphatidylinositols (PI3P) that bind PKB pleckstrin homology (PH) domain promoting PKB activation through its translocation from the cytosol to the plasma membrane, conformational change and final phosphorylation. Thus, inhibitors that target PI3Ks and its downstream effectors, including Akt are potentially relevant for cancer therapy.1
New sulfoquinovosylacylglycerols (SQAG) analogues 12-4 are currently investigated as potential Akt inhibitors, their structure being easily reconducted to PI3P. Here, the synthesis of new anionic glycoglycerolipids 2 derived from the sulfoglycolipids 1 as PI3P analogues targeting the PKB PH domain will be reported. In particular, a series of analogues of natural SQAG in which glucose is -linked to the 2 position of an acylglycerol and a carboxyl replaces the sulfonate group, together with some simpler related -glucuronides, will be shown
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