Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Renal toxicity produced by paraquat involves the generation of reactive oxygen species (ROS) which can overwhelm antioxidant defences, leading to oxidant injury. However, there are conflicting reports regarding the activity and/or expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during oxidative stress injury. This study investigated the activity and expression of these enzymes in a renal epithelial cell line following exposure to paraquat. Confluent NRK-52E cells were incubated with increasing concentrations of paraquat (1-100mM) for up to 24 hours. Renal cell death was determined by measurement of lactate dehydrogenase release. Oxidant damage was determined via measurement of malondialdehyde formation and DNA strand breaks. The effects of paraquat on DNA and de novo protein synthesis were determined using radio-labelled thymidine and leucine respectively. ROS generation (superoxide anion and hydroxyl radical formation) was measured using nitro-bluetetrazolium and deoxyribose assays. Antioxidant enzyme activities and expression were measured using established biochemical assays and Western blot analysis. Exposure of confluent NRK-52E cells to paraquat resulted in significant cell death involving increased lipid peroxidation, DNA damage and inhibition of DNA and de novo protein synthesis. Renal cell injury and death were secondary to increased ROS generation. Incubation with paraquat reduced SOD and CAT activities; in contrast, GSH-Px activity increased significantly. Although SOD expression was significantly reduced, catalase expression was unaffected. These results indicate that paraquat mediates renal toxicity via oxidative stress involving both an increase in ROS generation and reductions in SOD and CAT activities with a concomitant reduction in SOD expression

Estimating Fixed Effects: Perfect Prediction and Bias in Binary Response Panel Models, with an Application to the Hospital Readmissions Reduction Program

The maximum likelihood estimator for the regression coefficients, β, in a panel binary response model with fixed effects can be severely biased if N is large and T is small, a consequence of the incidental parameters problem. This has led to the development of conditional maximum likelihood estimators and, more recently, to estimators that remove the O(T–1) bias in β^. We add to this literature in two important ways. First, we focus on estimation of the fixed effects proper, as these have become increasingly important in applied work. Second, we build on a bias-reduction approach originally developed by Kosmidis and Firth (2009) for cross-section data, and show that in contrast to other proposals, the new estimator ensures finiteness of the fixed effects even in the absence of within-unit variation in the outcome. Results from a simulation study document favourable small sample properties. In an application to hospital data on patient readmission rates under the 2010 Affo

Il ragionamento probabilistico nella diagnosi medica: sensibilità e insensibilità alle informazioni

Il giudizio diagnostico umano su problemi astratti sembra ricalcare, in parte, quanto previsto dai modelli formali della revisione delle conoscenze probabilistiche: alcuni esperimenti mostrano come anche individui non esperti siano in grado di accorgersi che un determinato insieme di indizi aumenta la probabilità di una determinata ipotesi e questa capacità appare tanto più evidente quanto più grande è il contenuto d’informazione di tali indizi. Tuttavia, l’analisi di alcuni risultati sperimentali evidenzia come i giudizi spontanei siano anche afflitti da tendenze psicologiche prive di validità formale. Ad esempio, alcune caratteristiche dei dati o delle ipotesi possono costituire dei veri e propri “indizi euristici”, cioè appigli psicologicamente salienti ma formalmente privi di alcun valore diagnostico. In compiti astratti, inoltre, gli individui non esperti tendono ad una sistematica sottostima dell’informazione disponibile, sottostimando o addirittura ignorando l’informazione veicolata dagli indizi assenti. I medici impegnati in compiti realistici si mostrano, al contrario, maggiormente sensibili all’informazione veicolata dai sintomi e sono più abili nel considerare l’importanza degli indizi assenti (come l’assenza di sintomi). Emerge, inoltre, sia per i medici sia per gli individui non esperti, la tendenza a sottostimare la forza di indizi fortemente contrari ad una diagnosi, evidenziando una tendenza alla conferma, che dovrebbe, quindi, essere tenuta in considerazione nella formazione metodologica del medico

Chemical-petrographic and isotopic characterization of the volcanic pavement along the ancient Appia route at the Aurunci Mountain Pass, Italy. Insights on possible provenance

The ancient Appia route was built across central-southern Italy between the fourth and second century before the common era (B.C.E.). At the Aurunci Mountain Pass, the route crosses carbonate ridges that provided the raw material used to pave the road in the first century C.E. This material was replaced with lava blocks of unknown origin in the third century C.E. The study area is at least 50 km from the main volcanic centers along the peri-Tyrrhenian side of Italy, such as the Colli Albani, Roccamonfina, and Middle Latin Valley volcanoes. The main objective of this research was the chemical–petrographic and isotopic characterization of rock samples from the Appia flagstones to unravel their possible provenance. The analytical procedure included scanning electron microscope and electron microprobe analyses and 87Sr/86Sr–143Nd/144Nd isotopic measurements. Samples taken from unknown quarries found in the Middle Latin Valley volcanic field underwent the same analyses. After comparing the analysis results with data from the literature, the most likely source area was identified with the Roccamonfina precaldera ultrapotassic sequence. The availability and use of volcanic resources for the construction and maintenance of the ancient Appia route in the investigated territories are only outlined in this work and deserve further study

Understanding rock materials exploitation along the Ancient Appia route by means of integrated geoarchaeological and microstratigraphic analyses

A comparison between Mesozoic carbonates and ancient Roman ashlars was performed by microstratigraphic analyses to complete a geoarcheological characterization of a rock cave system featuring the Ancient Appia route where it crosses the Aurunci ridge along the San Andrea Valley, between the modern villages of Fondi and Itri (southern Latium). This research is part of a FIRB project led by the CNR-ITABC in collaboration with the Second University of Naples - Department of Literature and Cultural Heritage, to which other Universities, CNR Research Institutes and private societies have occasionally collaborated. The understanding of the anthropogenic landscape modifications required a multidisciplinary approach. Results show the preferential use of coarsegrained Aptian limestones on the northern part of the road tract and Cenomanian-Turonian limestones in correspondence of the southern zone