825 research outputs found

    Quercetin inhibits the sulfation of R(-)-apomorphine in human brain

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    The first aim of this investigation was to study the sulfation of R(-)-apomorphine in human brain. The second aim was to investigate the inhibition of R(-)-apomorphine sulfation by quercetin in human brain. R(-)-apomorphine is hereafter referred to as apomorphine. Apomorphine sulfation was measured in 5 brain specimens; 3 derived from the frontal cortex and 2 derived from the temporal cortex. The rate of apomorphine sulfation was 5.6 +/- 4.3 pmol/min/mg. The activities of SULT1A1 and SULT1A3, which were also measured in these samples, were 11 +/- 9.1 and 2.6 +/- 1.7 pmol/min/mg, respectively. The rate of apomorphine sulfation correlated with the activity of SULT1A1 (r= 0.989; p = 0.002) and SULT1A3 (r = 0.973; p = 0.005). Apomorphine sulfotransferase followed Michaelis-Menten kinetics, the Km (mean +/- SD) and V-max values (mean +/- SD) of which, measured in 5 brain samples, were 32 +/- 7.3 muM and 8.9 +/- 7.9 pmol/min/mg, respectively. Quercetin was a potent inhibitor of apomorphine sulfation with an IC50 value, measured in 5 brain samples, of 16 +/- 2.3 nM. The inhibition mechanism of quercetin using apomorphine sulfation in 5 brain samples was mixed, non-competitive with a K-i and Kies (mean +/- SD) of 16 +/- 4.1 and 87 +/- 37 nM, respectively (p = 0.008). The intrinsic clearance value of apomorphine (mean SD) was 247 +/- 170 ml/min/mg(-1) and was decreased to 100 +/- 85 ml/min/mg(-1) (p < 0.01) in the presence of 25 nM quercetin. In conclusion, apomorphine is sulfated in human brain. Sulfation might reduce the level of apomorphine in human brain and be a factor limiting the effect of this drug. Quercetin is a potent inhibitor of apomorphine sulfation and may inhibit the sulfation of apomorphine in human brain in vivo

    Il ruolo del sistema nazionale di allerta precoce nella tutela della salute pubblica: strategie istituzionali e contributo tossicologico-forense per il contrasto alla diffusione delle nuove sostanze psicoattive

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    Lo scopo della presente tesi è di esporre il ruolo e le attività svolte dal Sistema Nazionale di Allerta Precoce (SNAP), istituito nel 2009 dal Dipartimento per le Politiche Antidroga (DPA) e coordinato dal punto di vista operativo e scientifico, a partire da giugno 2016, dall’Istituto Superiore di Sanità (ISS). Si descrive l’organizzazione del flusso di informazioni e i dati epidemiologici relativi alla diffusione delle nuove sostanze psicoattive (NSP) sul territorio europeo e nazionale, attraverso le segnalazioni precoci della loro comparsa sul mercato clandestino e la tempestiva comunicazione di eventuali stati di allerta relativi a fenomeni potenzialmente pericolosi per la salute pubblica strettamente correlati al consumo di questi composti. Obiettivo della tesi è anche l’illustrazione delle strategie messe in atto per far fronte alla rapida diffusione delle NSP nella Unione Europea e sul territorio italiano, presentando il supporto biotossicologico fornito dalla Unità Operativa di Tossicologia Forense dell’Università Sapienza di Roma (UO di Biotossicologia), nell’ambito delle attività del Sistema di Allerta. A tale proposito verrà descritto il ruolo della UO di Biotossicologia nella revisione delle Comunicazioni provenienti dall’Osservatorio Europeo sulle Droghe e sulle Tossicodipendenze e la preparazione delle Informative relative ai sequestri operati dalle forze dell’ordine su territorio nazionale. Verrà inoltre esposto il contributo tecnico analitico offerto dalla suddetta Unità Operativa nei casi di accertamenti tossicologici effettuati su materiale non biologico oggetto di sequestro. Infine verranno presentate le revisioni sistematiche della letteratura internazionale, realizzate dall’Unità Operativa di Tossicologia Forense in merito alle NSP di maggiore diffusione e pericolosità sul territorio nazionale, sulla base dell’esperienza tecnico scientifica maturata durante la collaborazione con lo SNAP. Capitolo 1: viene illustrata l’organizzazione del Sistema Nazionale di Allerta Precoce (SNAP) ed il ruolo cruciale che tale piattaforma riveste nella tutela della salute pubblica, coordinando lo scambio rapido di informazioni tra l’Osservatorio Europeo sulle droghe e sulle tossicodipendenze, le Forze dell’Ordine che operano i sequestri su territorio nazionale ed i Centri Collaborativi (ospedali, dipartimenti di emergenza, Ser.D.), al fine di facilitare la precoce individuazione di nuove sostanze psicoattive sul mercato clandestino e supportare le attività medico-sanitarie nel trattamento in emergenza di soggetti in stati di intossicazione acuta da NSP. Capitolo 2: si introduce il concetto di nuova sostanza psicoattiva, effettuando una disamina della struttura chimica delle principali classi di appartenenza di questi composti ed approfondendo la delicata problematica dello stato di emergenza socio-sanitaria connesso al loro consumo. Capitolo 3: viene descritto il supporto biotossicologico e tecnico analitico che l’Unità Operativa di Tossicologia Forense offre all’interno dello SNAP nella supervisione della documentazione e degli eventi che sono oggetto di attività del Sistema, sia a livello europeo che nazionale. Vengono, inoltre, presentate le revisioni sistematiche della letteratura internazionale realizzate dall’UO, in merito alle NSP maggiormente diffuse nel nostro Paese e che rappresentano ad oggi un grave rischio per la salute pubblica. Capitolo 4: è dedicato alle conclusioni del lavoro di tesi, alle criticità del complesso sistema dedicato alla prevenzione ed alla lotta alla diffusione delle NSP ed agli obiettivi futuri, prevalentemente focalizzati sulla messa a punto di nuovi strumenti scientifici e legislativi sempre più efficaci per affrontare e combattere l’emergenza sociale e medico-sanitaria causata dalla indiscriminata espansione di queste nuove sostanze

    Sulfation of R (.) apomorphine in the human liver and duodenum, and its inhibition by mefenamic acid salicylic acid and quercetin

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    The aims were to study the sulfation of R-(-)-apomorphine (hereafter apomorphine) in the human liver and duodenum, and to study the rate of inhibition of apomorphine sulphation by mefenamic acid, salicylic acid and quercetin also in the human liver and duodenum

    Comparative evaluation of the accuracy of linear measurements between cone beam computed tomography and 3D microtomography.

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    Objective. The aim of this study was to evaluate the influence of artifacts on the accuracy of linear measurements estimated with a common cone beam computed tomography (CBCT) system used in dental clinical practice, by comparing it with microCT system as standard reference. Materials and Methods. Ten bovine bone cylindrical samples containing one implant each, able to provide both points of reference and image quality degradation, have been scanned by CBCT and microCT systems. Thanks to the software of the two systems, for each cylindrical sample, two diameters taken at different levels, by using implants different points as references, have been measured. Results have been analyzed by ANOVA and a significant statistically difference has been found. Results and Discussion. Due to the obtained results, in this work it is possible to say that the measurements made with the two different instruments are still not statistically comparable, although in some samples were obtained similar performances and therefore not statistically significant. Conclusion. With the improvement of the hardware and software of CBCT systems, in the near future the two instruments will be able to provide similar performances.OBJECTIVE: The aim of this study was to evaluate the influence of artifacts on the accuracy of linear measurements estimated with a common cone beam computed tomography (CBCT) system used in dental clinical practice, by comparing it with microCT system as standard reference. MATERIALS AND METHODS: Ten bovine bone cylindrical samples containing one implant each, able to provide both points of reference and image quality degradation, have been scanned by CBCT and microCT systems. Thanks to the software of the two systems, for each cylindrical sample, two diameters taken at different levels, by using implants different points as references, have been measured. Results have been analyzed by ANOVA and a significant statistically difference has been found. RESULTS AND DISCUSSION: Due to the obtained results, in this work it is possible to say that the measurements made with the two different instruments are still not statistically comparable, although in some samples were obtained s

    Microtomographic and morphometric characterization of a bioceramic bone substitute in dental implantology

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    In recent years, bone tissue regeneration studies have led to a deeper knowledge of chemical and structural features of the best biomaterials to be used as replacements for lost bone structures, with the autologus bone still today the only graft material able to ostegenerate, osteinduct and/or osteoconduct. The difficulties of the small available amount of autologus bone, together with morbidity of a second surgical operation on the same patient, have been overcome using both synthetic and biologic substitute bones. The possibility of investigating morphometric characteristics of substitute bones makes it possible to evaluate the predictability of regenerative processes and, so far, a range of different methods have been used for the purpose. X-ray microtomography (micro-CT) is a miniaturized form of conventional tomography, able to analyze the internal structure of small objects, performing three-dimensional images with high spatial resolution (<10 micron pixel size). For a correct analysis, samples need not be altered or treated in any way, as micro-CT is a non-invasive and non-destructive technique. It shows promising results in biomaterial studies and tissue engineering. This work shows the potential applications of this microtomographic technique by means of an in vitro analysis system, in characterizing morphometric features of human bone tissue, and contributes to the use of this technique in studies concerning biomaterials and bioscaffolds inserted in bone tissue.In recent years, bone tissue regeneration studies have led to a deeper knowledge of chemical and structural features of the best biomaterials to be used as replacements for lost bone structures, with the autologus bone still today the only graft material able to ostegenerate, osteinduct and/or osteoconduct. The difficulties of the small available amount of autologus bone, together with morbidity of a second surgical operation on the same patient, have been overcome using both synthetic and biologic substitute bones. The possibility of investigating morphometric characteristics of substitute bones makes it possible to evaluate the predictability of regenerative processes and, so far, a range of different methods have been used for the purpose. X-ray microtomography (micro-CT) is a miniaturized form of conventional tomography, able to analyze the internal structure of small objects, performing three-dimensional images with high spatial resolution (< 10 micron pixel size). For a correct

    Job Shop Scheduling with Two Jobs and Nonregular Objective Functions

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    We consider the job shop scheduling problem with two jobs. We consider a broad class of non-regular, quasi-convex functions of the completion time of the two jobs. We show that the optimal solution, for this class of objective functions, can be computed in O (r log r + log H) time, where r is the number of operation pairs using the same machine, and H is the maximum operation processing time

    Silhouette portrait of John R. Drexel III

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    A profile-view silhouette portrait of John R. Drexel III. Inscription on the back reads, "John R. Drexel, 3rd.
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