Valutazione farmacocinetica dell'enrofloxacina dopo singola somministrazione intramuscolare in tartarughe Trachemis Scripta Scripta

RIASSUNTO Parole chiave: Enrofloxacina, tartaruga, Trachemis Scripta Scripta, intramuscolare, farmacocinetica. Le concentrazioni sanguigne e la farmacocinetica di enrofloxacina e del suo metabolita ciprofloxacina (fluorochinoloni, inibitori della DNA girasi) sono state determinate in 14 tartarughe Trachemis Scripta Scripta, dopo somministrazione intramuscolare alla dose 10 mg/kg di enrofloxacina. Il sangue è stato prelevato dai seni venosi della zona cervicale prima della somministrazione e a 0,5, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 e 192 ore dopo la somministrazione. La concentrazione di enrofloxacina e ciprofloxacina è stata determinata usando una metodica FL-HPLC. La concentrazione massima media dell’enrofloxacina e della ciprofloxacina riscontrata nel sangue (C max) è stata rispettivamente 10,3 μg/mL e 0,3 μg/mL. Il tempo di emivita medio riscontrato è 47,6 ore per l’enrofloxacina e 37,4 ore per la ciprofloxacina, mentre il tempo durante il quale il farmaco permane nell’organismo è 56,6 ore per l’enrofloxacina e 59 ore per la ciprofloxacina. Questo studio ha dimostrato che tale dosaggio è ottimale nel trattamento di infezioni batteriche nelle tartarughe. La cinetica lunga nel tempo è vantaggiosa da un punto di vista terapeutico, mentre è da chiarire se essa può essere vantaggiosa nel caso in cui le tartarughe entrino a far parte della catena alimentare umana. ABSTRACT Key words: enrofloxacin, turtle, Trachemis Scripta Scripta, intramuscular, pharmacokinetics. Blood concentrations of enrofloxacin and his active metabolite ciprofloxacin (fluoroquinolones that inhibit DNA gyrase), were determined in 14 turtles Trachemis Scripta Scripta, after intramuscular administration of enrofloxacin 10 mg/kg. The blood was collected from cervical sinus prior drug administration and at 0.5, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours after administration. The concentrations of enrofloxacin and ciprofloxacin were detected by an FL-HPLC method. The mean peak’s concentration of enrofloxacin and ciprofloxacin (C max) is 10.3 μg/mL and 0,3 μg/mL respectively. The mean half-life was 47.6 h for enrofloxacin and 37.4 h for ciprofloxacin, while the mean residence time is 56.6 h for enrofloxacin and 59 h for ciprofloxacin. The present study demonstrated that this dosage is suitable for turtles affected by bacterial infections. If from one side the long-lasting kinetics profile of enrofloxacin is advantageous in therapy, on the other side it might be of concern if treated turtles are used as food producing animal

Valutazione teorica e sperimentale di tecniche di fito-biorimediazione applicate a sedimenti di dragaggio

Studio teorico e sperimentale di tecniche emergenti quali la fitorimediazione, riguardanti la bonifica di sedimenti dragati, contaminati sia da idrocarburi che metalli pesanti, mediante l'utilizzo di piante e lombrichi. Lo studio prevede anche la modellazione matematica dei processi coinvolti

Flavoprotein monooxygenases for oxidative biocatalysis: recombinant expression in microbial hosts and applications

External flavoprotein monooxygenases comprise a group of flavin-dependent oxidoreductases that catalyze the insertion of one atom of molecular oxygen into an organic substrate and the second atom is reduced to water. These enzymes are involved in a great number of metabolic pathways both in prokaryotes and eukaryotes. Flavoprotein monooxygenases have attracted the attention of researchers for several decades and the advent of recombinant DNA technology caused a great progress in the field. These enzymes are subjected to detailed biochemical and structural characterization and some of them are also regarded as appealing oxidative biocatalysts for the production of fine chemicals and valuable intermediates toward active pharmaceutical ingredients due to their high chemo-, stereo-, and regioselectivity. Here, we review the most representative reactions catalyzed both in vivo and in vitro by prototype flavoprotein monooxygenases, highlighting the strategies employed to produce them recombinantly, to enhance the yield of soluble proteins, and to improve cofactor regeneration in order to obtain versatile biocatalysts. Although we describe the most outstanding features of flavoprotein monooxygenases, we mainly focus on enzymes that were cloned, expressed and used for biocatalysis during the last yearsFil: Ceccoli, Romina Denis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Bianchi, Dario Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Rial, Daniela Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

The expressive power of pooling in Graph Neural Networks

In Graph Neural Networks (GNNs), hierarchical pooling operators generate local summaries of the data by coarsening the graph structure and the vertex features. Considerable attention has been devoted to analyzing the expressive power of message-passing (MP) layers in GNNs, while a study on how graph pooling affects the expressiveness of a GNN is still lacking. Additionally, despite the recent advances in the design of pooling operators, there is not a principled criterion to compare them. In this work, we derive sufficient conditions for a pooling operator to fully preserve the expressive power of the MP layers before it. These conditions serve as a universal and theoretically-grounded criterion for choosing among existing pooling operators or designing new ones. Based on our theoretical findings, we analyze several existing pooling operators and identify those that fail to satisfy the expressiveness conditions. Finally, we introduce an experimental setup to verify empirically the expressive power of a GNN equipped with pooling layers, in terms of its capability to perform a graph isomorphism test

Bonifica e recupero di sedimenti marini di dragaggio mediante tecniche non convenzionali

La presente Tesi riporta i risultati scaturiti dall’applicazione a sedimenti contaminati di dragaggio portuale, di una tecnica naturale di decontaminazione non convenzionale, che prevede l’utilizzo combinato di piante (fitoremediazione) e lombrichi (biorimediazione), previo condizionamento fisico-strutturale della matrice da trattare (sedimento marino). Generalmente i sedimenti dragati dai canali interni di zone portuali o che raccolgono acque superficiali miste (agricole, artigianali e urbane) manifestano bassi livelli di inquinamento organico ed inorganico, per cui si può ipotizzare l’uso di piante comuni, acquatiche e non, reperibili in loco per la loro bonifica. La tecnica presentata risulta non impattante, applicabile in molti ecosistemi agrari, efficiente per migliorare, dal punto di vista geologico e biofisico, la matrice suolo o sedimento che vengono ad assume le caratteristiche di un tecno-suolo utile ai fini di un ripristino ambientale, paesaggistico o ricreativo. Tale tecnica consente di effettuare senza alcun rischio ambientale e a costi competitivi rispetto ad altre forme di trattamento e allo smaltimento, un intervento di bonifica delle matrici ambientali inquinate da metalli pesanti, idrocarburi, pesticidi, basandosi sull’uso di specie arbustive e/o erbacee, opportunamente selezionate in funzione della tipologia fisico-meccanica della matrice e delle sue caratteristiche chimiche-biologiche. L’efficacia del trattamento è dovuta all’azione delle radici delle piante che, a livello di rizosfera, attivano i processi biochimici per metabolizzare gli inquinanti organici, anche quelli più recalcitranti. Tali processi sono fondamentalmente svolti dalle numerose specie microbiche sostenute dalla pianta con i suoi essudati radicali energetici e dalla diffusione di ossigeno attraverso la porosità del sistema suolo-radice. L’abbondante attività biologica a livello di rizosfera, e la presenza continua di essudati radicali e sostanza umica (acidi umici) favorisce inoltre la solubilizzazione dei metalli pesanti e quindi il loro assorbimento nei tessuti vegetali. Tutto questo è sostenuto dalla presenza attiva dei lombrichi, localizzati appunto nella rizosfera. Considerata l’abbondante biomassa vegetale sviluppata sulla matrice da bonificare, generalmente si ha un lieve e non significativo aumento delle concentrazioni di metalli nelle parti epigee della pianta, considerazione che fa escludere qualsiasi rischio sanitario ambientale, applicando tale tecnica su scala reale. Qualora si ravvisasse un iper-accumulo, come ad esempio avviene nelle piante iper-accumulatrici cresciute su matrici industriali a medio/alto inquinamento, si dovrà procedere alla rimozione della pianta con periodici sfalci da conferire poi ad incenerimento, con successivo recupero energetico. Resta comunque il fatto che i volumi sono notevolmente inferiori (e quindi i costi di smaltimento) a quelli che si avrebbero se a discarica dovessero finire i volumi di matrice (terreno o sedimento) non trattati. La presente Tesi scaturisce dalla stretta collaborazione con l’Istituto per lo Studio degli Ecosistemi del CNR di Pisa, applicando la tecnica esposta a sedimenti marini dragati dal Porto di Livorno ed utilizzando particolari essenze vegetali resistenti alla salinità (Tamarix gallica, Paspalum vaginatum e Trifolium alexandrinum), ammendanti organici (sostanze umiche) e lombrichi (Eisenia fetida). Lo studio si è basato su un progetto di ricerca di cooperazione Italia-Israele, finanziato dal Ministero Italiano dell’Ambiente e della Tutela del Territorio e del Mare, finalizzato a studiare la fattibilità di un approccio integrato per la decontaminazione di sedimenti contaminati. I risultati ottenuti hanno mostrato che la tecnica di trattamento biologico non convenzionale e che potremo definire come tecnica di fitorimediazione modificata o fito-biorimediazione, ha consentito la fitoestrazione di metalli pesanti e la riduzione degli idrocarburi fino a livelli compatibili con la normativa ambientale italiana per siti ad uso verde pubblico, privato e residenziale (D.Lgs 152/2006). La selezione di particolari essenze ha consentito la colonizzazione del sedimento da parte delle radici e così una migliore infiltrazione delle acque di pioggia simulata. Il miglioramento della porosità ha permesso una migliore circolazione di aria ed acqua utili a sostenere i processi biologici di decontaminazione e fitoestrazione dei metalli pesanti, oltre naturalmente a determinare un netto miglioramento fisico-strutturale della matrice limo-argillosa ed impaccata di partenza. La matrice sarebbe così pronta per un possibile riutilizzo in opere di ripristino ambientale, per attività di recupero e miglioramento rurale o per la lotta alla desertificazione, operazioni in molti casi necessarie ma che risultano spesso limitate dalla non disponibilità di matrici di idonea qualità ed adeguata quantità. A tale studio ha fatto recentemente seguito il finanziamento da parte dell’Unione Europea del progetto triennale Eco-Innovation “AGRIPORT” cofinanziato dal Ministero Italiano dell’Ambiente, finalizzato a portare le tecniche di fitorimediazione precedentemente sperimentate, ad una fase applicativa, compreso il riuso a fini produttivi

Optimized Collaborative Brain-Computer Interfaces for Enhancing Face Recognition

: The aim of this study is to maximize group decision performance by optimally adapting EEG confidence decoders to the group composition. We train linear support vector machines to estimate the decision confidence of human participants from their EEG activity. We then simulate groups of different size and membership by combining individual decisions using a weighted majority rule. The weights assigned to each participant in the group are chosen solving a small-dimension, mixed, integer linear programming problem, where we maximize the group performance on the training set. We therefore introduce optimized collaborative brain-computer interfaces (BCIs), where the decisions of each team member are weighted according to both the individual neural activity and the group composition. We validate this approach on a face recognition task undertaken by 10 human participants. The results show that optimal collaborative BCIs significantly enhance team performance over other BCIs, while improving fairness within the group. This research paves the way for practical applications of collaborative BCIs to realistic scenarios characterized by stable teams, where optimizing the decision policy of a single group may lead to significant long-term benefits of team dynamics

Gene-specific methylation profiles in BRCA-mutation positive and BRCA-mutation negative male breast cancers

Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs. We examined 69 MBCs, paired blood samples, and 15 normal tissues for promoter methylation of hTERT, ESR1, RASSF1, AR, MYC and WNT1 genes. MBCs showed higher gene promoter methylation levels compared to paired blood and normal breast samples. Significantly higher RASSF1 methylation levels were observed in association with BRCA1/2 mutations, HER2 expression and high tumor grade. Significantly higher AR methylation levels were observed in BRCA1/2 wild-type cases and higher WNT1 methylation levels in PR negative cases. Overall, our results indicate that alterations in gene methylation profiles are common in MBC and that methylation pattern of tumor-associated genes may allow for the identification of MBC molecular subgroups, that could have implications in clinical management of MBC patients

Efficacy of non-surgical periodontal therapy in reducing periodontal indexes in kidney-transplant patients

Efficacy of non-surgical periodontal therapy in reducing periodontal indexes in kidney-transplant patients. I. Casula, L. Zanardini*, M. Bianchi, V. Spotti, E. Marchesini Department of Medical and Surgical Specialties and Public Health Dentale - Dental School – University of Brescia, Italy Aim: kidney-transplant patient must take cyclosporine-A and calcium channel blockers chronically. Both medicines involve a gingival overgrowth (G.O.) as a collateral effect and this is due to their dosage: it appears 1-3 months after the beginning of the therapy. The prevalence of the G.O. is 84%. The G.O. originates from anterior interdental papilla and it appears as a red and soft tumefaction, that becomes more fibrinous as time goes by. The G.O. takes place in apical-coronal verse and also in vestibular-lingual verse and it looks like a gingival hypertrophy and hyperplasia, which is due to an abnormal increase of the number of fibroblasts into gingival connective tissue. The G.O. involves a great aggregation of extracellular Matrix, or less degradation of it, or both these processes simultaneously. The G.O. leads to the formation of pseudopockets, which interfere with the correct oral hygiene practices. This condition gives rise to mature plaque retention , that leads to infection, inflammation and the increase of the G.O. This condition becomes worse because of bad pre-transplant oral hygiene state. The aim of this study is to estimate the efficacy of non-surgical periodontal therapy in reducing the G.O. in kidney-transplant patient. Materials and methods: a sample of 32 simple random kidney transplant subjects was enrolled in this study (mean age: 58,44; range: 33-81, 21 m., 11f.). All of them were taking cyclosporine A and calcium channel blockers. Patients taking idantoine, pregnant women, patients suffering from diabetes mellitus or people who have undergone gingival surgery were excluded. The study started on November 2012 and finished on September 2013. Periodontal indexes and Professional oral hygiene practices were performed by the same dental hygienist. The plaque, calculus, bleeding, G.O. and probing depth indexes were evaluated at T0, T1, T2, T3 (at 0, 2, 4, 6 months respectively). Every time the same oral hygiene protocol was applied: non-surgical periodontal therapy with ultrasonic instruments above and below the gum. Results: 787 teeth analysed and 4722 periodontal sites probed. Plaque index (PI), calculus index (CI) and bleeding index (BoP) show significant statistical reduction (p<0,0001). T-test was used for statistic analysis. PI at T0=82,09%, at T3=29,89%/ CI at T0=53,44%, at T3=23,70%/ BoP at T0=71,98%, at T3=26,18%. Probing depth (PD), at six-monthly control , shows a significant statistical reduction (p<0,0001). PD 1-3 mm at T0=16,58%, at T3=30,45%. PD 4-6mm at T0=74,06%, at T3=64,70%. PD 7-9 mm at T0=9,36%, at T3=4,85%. G.O. At T0=54,93%, at T3=44,98%, with a significant statistical reduction (p<0,0001). Conclusions: the applied oral hygiene protocol is simple but effective in reducing drug-induced gingival overgrowth in kidney-transplant patient taking Cyclosporine-A. These clinic results assure a better oral health, improving the quality of life form an aesthetic and functional point of view

Improving P300 Speller performance by means of optimization and machine learning

Brain-Computer Interfaces (BCIs) are systems allowing people to interact with the environment bypassing the natural neuromuscular and hormonal outputs of the peripheral nervous system (PNS). These interfaces record a user's brain activity and translate it into control commands for external devices, thus providing the PNS with additional artificial outputs. In this framework, the BCIs based on the P300 Event-Related Potentials (ERP), which represent the electrical responses recorded from the brain after specific events or stimuli, have proven to be particularly successful and robust. The presence or the absence of a P300 evoked potential within the EEG features is determined through a classification algorithm. Linear classifiers such as SWLDA and SVM are the most used for ERPs' classification. Due to the low signal-to-noise ratio of the EEG signals, multiple stimulation sequences (a.k.a. iterations) are carried out and then averaged before the signals being classified. However, while augmenting the number of iterations improves the Signal-to-Noise Ratio (SNR), it also slows down the process. In the early studies, the number of iterations was fixed (no stopping), but recently, several early stopping strategies have been proposed in the literature to dynamically interrupt the stimulation sequence when a certain criterion is met to enhance the communication rate. In this work, we explore how to improve the classification performances in P300 based BCIs by combining optimization and machine learning. First, we propose a new decision function that aims at improving classification performances in terms of accuracy and Information Transfer Rate both in a no stopping and early stopping environment. Then, we propose a new SVM training problem that aims to facilitate the target-detection process. Our approach proves to be effective on several publicly available datasets.Comment: 32 pages, research articl