123 research outputs found
Der Mensch und die (anderen) Tiere, in (edited by Assunta Varrone and Peter Nickl), Lit Verlag, Berlin 2016, pp. 178-184
No full textDiscovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold
No full textA new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with the P1′ aromatic portion and a d-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead molecule. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and MMP-7
Insulin enhances vascular adhesion molecule (VCAM-1) expression in human cultured endothelial cells through a pro-atherogenic p38MAP-kinase mediated pathway.
No full textAims/hypothesis. Although hyperinsulinaemia in Type 2 diabetes in states of insulin resistance is a risk factor for atherosclerotic vascular disease, underlying mechanisms are poorly understood. We tested the hypothesis that insulin increases monocyte-endothelial interactions, which are implicated in atherosclerosis.
Methods. We treated human umbilical vein endothelial cells with insulin (10(-10) to 10(-7) mol/l) for 0 to 24 h. To dissect potentially implicated signal transduction pathways, we treated endothelial cells with known pharmacological inhibitors of two distinct insulin signalling pathways: the phosphatidylinositol-3'-kinase (PI3'-kinase) inhibitor wortmannin (3x10(-8) to 10(-6) mol/l), involved in insulin-induced endothelial nitric oxide synthase stimulation, and the p38 mitogen-activated protein (p38MAP) kinase inhibitor SB-203580 (10(-7) to 2x10(-6) mol/l). We measured adhesion molecule expression by cell surface enzyme immunoassays and U937 monocytoid cell adhesion in rotational adhesion assays.
Results. At pathophysiological concentrations (10(-9) to 10(-7) mol/l), insulin concentration-dependently induced vascular cell adhesion molecule (VCAM)-1 (average increase: 1.8-fold) peaking at 16 h. By contrast, the expression of intercellular adhesion molecule-1 and E-selectin were unchanged. The effect on VCAM-1 was paralleled by increased U937 cell adhesion. In the absence of cytotoxicity, wortmannin significantly potentiated the effect of insulin alone on VCAM-1 surface expression and monocytoid cell adhesion, whereas SB-203580 (10(-6) mol/l) completely abolished such effects.
Conclusions/interpretation. These observations indicate that insulin promotes VCAM-1 expression in endothelial cells through a p38MAP-kinase pathway, amplified by the PI3'-kinase blockage. This could contribute to explaining the increased atherosclerosis occurring in subjects with hyperinsulinaemia, or in states of insulin resistance, which feature a defective PI3'-kinase pathway
Homocysteine induces VCAM-1 gene expression through NF-κB and NAD(P)H oxidase activation: Protective role of Mediterranean diet polyphenolic antioxidants
No full textHyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-κB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-κB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 μmol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-κB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-κB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IκB-α and IκB-β by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47 phox subunit. NF-κB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10 -6 mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-κB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage
Homocysteine induces VCAM-1 gene expression through NF-κB and NAD(P)H oxidase activation: Protective role of Mediterranean diet polyphenolic antioxidants
No full textHyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-κB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-κB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 μmol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-κB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-κB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IκB-α and IκB-β by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47 phox subunit. NF-κB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10 -6 mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-κB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage
L'economia aziendale
No full textL’economia aziendale è una scienza che elabora le conoscenze e le teorie utili per il governo economico di organizzazioni e sistemi sociali all’interno dei quali si svolge un’attività economica. Per apprezzare appieno la portata di questa disciplina è fondamentale comprendere il significato dei due termini che la compongono, ossia “economia” ed “azienda”. Al concetto di economia, e più nello specifico, dell’agire economico della persona è dedicato il paragrafo 1.1. La vita dell’uomo infatti è, da sempre, caratterizzata dal sorgere di bisogni e dalla ricerca del loro appagamento. La nascita ed il progressivo sviluppo dell’attività economica trova fondamento proprio nella necessità di soddisfare i bisogni dell’uomo che con il trascorrere del tempo sono diventati sempre più articolati e complessi (paragrafo 1.1.1) e dipendono dal consumo e dall’utilizzo di beni (paragrafo 1.1.2). A tal riguardo avremo modo di vedere come ogni teoria economica, proprio perché orientata a studiare il comportamento umano, richiede la definizione di una teoria dei bisogni e dei processi decisionali sui quali si articola l’attività di produzione e consumo. Il paragrafo 1.1.3 sarà dedicato alla presentazione dei principali modelli sviluppati negli studi economici per definire le caratteristiche dei processi decisionali distinguendo, da un lato i processi decisionali individuali — ovvero adottati dalle singole persone — e dall’altro quelli collettivi, ossia sviluppati all’interno delle organizzazioni. Proprio il concetto di organizzazione, e a seguire quello di azienda, costituiscono il contenuto principale del paragrafo 1.2. L’attività economia di produzione e consumo — oggetto del paragrafo 1.2.1 — nelle società contemporanee, infatti, è svolta in misura prevalente all’interno di istituti di diversa natura, costituiti per agevolare le modalità di soddisfacimento dei bisogni delle persone. I principali istituti nei quali si svolge l’attività economica sono descritti nel paragrafo 1.2.2 e saranno ripresi in maniera più approfondita — nei loro tratti distintivi — nel capitolo 2. Lo svolgimento dell’attività economica (di produzione) realizzata nelle organizzazioni richiede la disponibilità e l’impiego di una moltitudine di fattori da impiegare nella produzione. Tra i vari fattori produttivi necessari per lo svolgimento dell’attività economica, tuttavia, nella tradizione degli studi aziendali, il lavoro e il capitale assumono un ruolo centrale nelle organizzazioni, tanto da essere considerati “condizioni primarie di produzione” come avremo modo di vedere nel paragrafo 1.2.3. Accanto al capitale e al lavoro, tuttavia, gli studi aziendali hanno riconosciuto, nel corso degli anni, l’affermarsi di un’ulteriore condizione fondamentale di produzione, identificata nella “conoscenza”. La conoscenza rappresenta oggi la principale condizione di produzione capace di spiegare il successo o l’insuccesso aziendale, i cui risvolti hanno dato origine alla così detta Knowledge Based View che sarà presentata nel paragrafo 1.3.1. Diventa a questo punto fondamentale comprendere il ruolo assunto dalla conoscenza e gli impatti che essa genera all’interno delle aziende al fine di consentirne un utilizzo razionale in modo che possa diventare patrimonio aziendale e non solo delle persone che in essa vi operano. Numerosi sono gli studi che hanno affrontato questi temi che saranno oggetto di approfondimento nel paragrafo 1.3.2. Proprio la centralità assunta dalla conoscenza nei processi aziendali ha portato allo sviluppo di una serie servizi basati sullo scambio e sulla condivisione di informazioni per l’utilizzo di un determinato bene. Tali servizi sono divenuti ormai parte integrante del nostro vivere quotidiano e delle nostre esperienze di consumo e rappresentano l’oggetto di studio della cosiddetta “sharing economy”, o economia della condivisione. Questi servizi e le motivazioni che hanno portato alla loro diffusione nel mercato saranno affrontati nella parte terminale del presente capitolo e in particolare nel paragrafo 1.3.3
Telemedicina applicata: il caso di studio di "Telemeliolab"
No full textIl progetto telemeliolab,in sperimentazione nella Regione Puglia,rappresenta un chiaro esempio di telemedicina applicata ai processi di deospetalizzazione in ambito oncologico.La piattaforma software progettuale consente di mettere in comunicazione la control room del policlinico di Bari con i pazienti affetti da gammapatia monoclonale sia MGUS (monoclonal component of undetermined signifiance) che mieloma multiplo potendo controllare a distanza l'evoluzione della patologia gestendo e pianificando gli esami ematochimici da effettuare nei laboratori di analisi aderenti al progett
When the investors speak: intellectual capital disclosure and the Web 2.0
No full textPurpose
The purpose of this paper is to investigate intellectual capital (IC) discussions held between investors using Web 2.0 tools. More precisely, this paper investigates the determinants of IC disclosures (ICDs) on internet stock message boards (IMBs).
Design/methodology/approach
Four hypotheses were developed and tested through content analysis of 60,996 messages posted on two main IMBs, Yahoo!Finance and TheLion.com, followed by descriptive statistics and logistic regression testing.
Findings
The findings show that Web 2.0 is bringing new opportunities to disclose IC. Traditional theories, such as agency, stakeholder, signalling, and legitimacy theory, cannot be applied to the Web 2.0 context. Therefore, a new approach that focusses more on the personal motivations for disclosing IC is called for. At a glance, the results show that IC is disclosed on IMBs, and several elements influence both the quantity and quality of those disclosures. Sometimes “trolls” disturb the dialogue and discourage participation by other investors. Conversely, online influencers facilitate ICD. To filter messages, the time of posting, the length of the messages, and the sentiment the messages contain should be considered along with the author of the message.
Originality/value
This paper contributes to the existing literature by investigating the IC disclosed on IMBs. The findings provide insights about how ICDs are developed using Web 2.0 tools
Erratum: The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCε inhibition (Proceedings of the National Academy of Sciences of the United States of America (2006) 103, 41, (15184-15189) DOI: 10.1073-pnas.0510086103)
No full text[No abstract available]Massaro M, 2006, P NATL ACAD SCI USA, V103, P15184, DOI 10.1073-pnas.05100861030
Studio e applicazione di una “Boekelheide like reaction” per la sintesi di composti eterociclici
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