52 research outputs found
Biotransformation and oxidative stress responses in rat hepatic cell-line (H4IIE) exposed to racemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP)
No full textPharmaceuticals such as racemate ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are highly detectable non-steroidal anti-inflammatory drugs (NSAIDs) in the aquatic environment and therefore are designated as one of the most emerging groups of pollutants that can affect environmental and human health. The potential impact of these pharmaceuticals was assessed for the first time in vitro using a rat hepatocellular carcinoma cell line (H4IIE). Cells were exposed to low and high concentrations of these drugs. Cytotoxicity was determined by MTT reduction assay; CYP1A1 transcriptional and enzymatic levels together with canonical oxidative stress responsive markers (GPx, GR, GST and CAT) were also investigated. Cells exposed to RS-KP and S(+)-KP did not show cytotoxicity effect at the concentrations tested. However, this study highlighted differences between RS-KP and S(+)-KP in most of the evaluated markers, showing compound-, concentration- and time-specific effect patterns which suggest a potential stereo-selective toxicity of these drugs
Statistical Methodologies for Integrated Circuits Design
No full textThe continuous scaling of physical dimensions has strongly increased circuit performance variability and the traditional corner-case methodology is becoming unreliable. As a consequence, there is an urgent need for new and more accurate statistical models. In this scenario, the purpose of this paper is twofold: 1) to give the reader the basic concepts of statistical modeling, and 2) to discuss a viable statistical approach that could be adopted into a traditional IC design flow for the next technology generations
Combination therapy with ciclosporin and etanercept in patients with psoriatic arthritis
No full textEcotoxicological properties of ketoprofen and the S(+)‐enantiomer (dexketoprofen): Bioassays in freshwater model species and biomarkers in fish PLHC‐1 cell line
No full textThe increased use of non-steroidal anti-inflammatory drugs (NSAIDs) has resulted in their ubiquitous presence in the environment. The toxicological properties of these two widely prescribed NSAIDs, namely - racemic ketoprofen (rac-KP) and its enantiomer S(+)-ketoprofen (dexketoprofen, DKP) were evaluated. Firstly, by acute and chronic toxicity tests using three representative model organisms (Vibrio fischeri, Pseudokirchneriella subcapitata and Ceriodaphnia dubia). Secondly, by evaluating the responses of biotransformation systems and multidrug resistance associated proteins (MRP1/MRP2) using the PLHC-1 fish hepatic cell-line. Toxicity data from both acute and chronic DKP exposure indicated higher sensitivity through inhibition of bioluminescence and algal growth and through increased mortality/immobilization compared to rac-KP exposure. The growth inhibition test showed that rac-KP and DKP exhibited different values for EC50 (240.2 μg/L and 65.6 μg/L, respectively). Furthermore, rac-KP and DKP did not exert cytotoxic effects in PLHC-1 cells, and produced compound-, time- and concentration-specific differential effects on CYP1A and GST levels. For CYP1A, the effects of rac-KP and DKP differed at transcriptional and catalytic level. Exposure to rac-KP and DKP modulated MRP1 and MRP2 mRNA levels and these effects were also dependent on compound, exposure time and concentration of the individual drug. The present study revealed for the first time, the interactions between these NSAIDs and key detoxification systems, and different sensitivity to the racemic mixture compared to its enantiomer. This article is protected by copyright. All rights reserved
Characterization of cholinesterase in Aphanius fasciatus (Teleostei, Cyprinodontidae) from Orbetello Lagoon (Tuscany, Italy)
No full textECOTOXICITY OF KETOPROFEN AND THE S(+)-ENANTIOMER (DEXKETOPROFEN): BIOASSAYS IN FRESHWATER MODEL SPECIES AND RESPONSES OF FISH PLHC-1 CELL-LINE
No full textThe ecotoxicological properties of ketoprofen (KP) or its enantiomer (dexketoprofen: DKP) in different experimental models were evaluated. Firstly, by acute and chronic toxicity tests using three representative model organisms (Vibrio fischeri, Pseudokirchneriella subcapitata and Ceriodaphnia dubia). Secondly, by evaluating the responses of biotransformation systems and multidrug resistance associated proteins (MRP1/MRP2) using the PLHC-1 fish hepatic cell-line. Data from both acute and chronic exposure of model organisms showed that DKP produced an higher toxicity (inhibition of bioluminescence and algal growth and crustacean mortality/immobilization), compared to KP; however effects were detectable only at high concentrations. The growth inhibition test with P. subcapitata showed that KP and DKP exhibited different values for the no observable effect concentration (NOEC) and lowest observable effect concentration (LOEC). Further, KP and DKP did not exert cytotoxic effects in PLHC-1 cells, showing compound-, time- and dose-dependent differential effects on phase I and II biotransformation systems. For CYP1A, cell exposure to KP and DKP differed at transcript and activity levels. Exposure to KP and DKP modulated MRP1 and MRP2 mRNA levels and these effects were also compound-, time- and dose-dependent. Overall, the present study revealed the interactions between these compounds and key detoxification systems, and different sensitivity to the racemic KP mixture compared to its S(+) enantiomer (DKP)
Novel organ-specific effects of Ketoprofen and its enantiomer, dexketoprofen on toxicological response transcripts and their functional products in salmon
No full textRacemic ketoprofen (RS-KP) and its enantiomer, dexketoprofen (S(+)-KP) are widely used non-steroidal anti-inflammatory drugs (NSAIDs), and commonly detected in the aquatic environment. The present study has evaluated the toxicological effects of RS-KP and S(+)-KP on biotransformation and oxidative stress responses in gills and liver of Atlantic salmon. Fish were exposed for 10 days using different concentrations of RS-KP (1, 10 and 100 μg/L) and S(+)-KP (0.5, 5 and 50 μg/L). Biotransformation and oxidative stress responses were analysed at both transcript and functional levels. In the gills, significant inhibitory effect at transcriptional and enzymatic levels were observed for biotransformation and oxidative stress responses. On the contrary, biotransformation responses were significantly increased at transcriptional and translational levels in the liver, while the associated enzymatic activities did not parallel this trend and were inhibited and further demonstrated by principal component analysis (PCA). Our findings showed that both compounds produced comparable toxicological effects, by producing organ-specific effect differences. RS-KP and S(+)-KP did not bioaccumulate in fish muscle, either due to rapid metabolism or excretion as a result of their hydrophobic properties. Interestingly, the inhibitory effects observed in the gills suggest that these drugs may not undergo first pass metabolism, that might result to downstream differences in toxicological outcomes
Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohort
No full textNon
Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohort
No full textVitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohor
IL REFERENDUM ‘PLEBISCITATO’. Per una storia dell’istituto nel primo trentennio repubblicano
No full textLa tesi ricostruisce la teoria giuridica, la genesi e l'evoluzione dell'istituto del referendum abrogativo nel primo trentennio dell'Italia del secondo dopoguerra. La parabola referendaria italiana ha segnato importanti passaggi politici e istituzionali, ma nonostante ciò è stata scarsamente analizzata dalla storiografia. L'autore, attraverso lo studio delle carte dei partiti, degli atti parlamentari, del dibattito politico sulla stampa quotidiana e sulle riviste, nonché dell'ampia riflessione giuridica sull'istituto, analizza nello specifico la relazione tra referendum e sistema dei partiti, gli effetti politici sul sistema e la tendenza ad utilizzarlo in una prospettiva plebiscitaria e antisistema. La tesi intende dimostrare come lo strumento, concepito dai costituenti come un correttivo del sistema parlamentare in grado di risolvere istituzionalmente momenti di conflitto tra parlamento e popolo rilegittimando il sistema, finì di fatto per essere un'arma contro il sistema dei partiti.
The thesis reconstructs the legal theory, origins, and evolution of the abrogative referendum in the first three decades of second post-war Italy. Although the trajectory of the Italian referendum marked significant political and institutional developments, it has nonetheless received limited attention from historiography. Through the analysis of party archives, parliamentary proceedings, political debates in daily newspapers and journals, as well as juridical debates on the institution, the author specifically examines the relationship between the referendum and the party system, its political impact on the system, and the tendency to employ it from a plebiscitary and anti-system perspective. Originally conceived by the framers of the Constitution as a corrective to the parliamentary system—capable of institutionally resolving moments of conflict between Parliament and the people while restoring legitimacy—the referendum ultimately became a weapon directed against the party system itself
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