Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

L’efficacia di Oberon contro il ragnetto rosso su cetriolo.

Prove di controllo contro il ragnetto rosso comune, Tetranychus urticae sono state condotte su cetriolo (varietà Merinda F1) al fine di valutare l’efficacia di Oberon 200 SC, a base di piromesifen, a confronto con altri acaricidi comunemente impiegati nelle stesse condizioni colturali. La prova è stata condotta in serra fredda, in agro di Zapponeta (FG), su coltura infestata per trasferimento del ragnetto rosso da altra serra, nel biennio 2009/2010. Il trattamento con Oberon è stato efficace principalmente contro le forme giovanili, manifestando un’azione pari o superiore a quella esercitata dagli altri formulati a base di abamectina, etoxazole e fenazaquin applicati a confronto

Preliminary results on the preferences of Callosobruchus maculatus on Apulian germplasm of Cicer arietinum

The susceptibility of six genotypes of Cicer arietinum L. (Fabaceae) to Callosobruchus maculatus (Fabr.) (Coleoptera: Bruchidae) was evaluated through comparative laboratory bioassays. The egg-laying amount, pattern of adult emergence, median development time and pre-adult mortality were assessed under free-choice and no-choice bioassays on three local genotypes (Altamura, Grumo Appula White and Grumo Appula Black) and three commercial varieties (Barraco, Sultano and standard of large-scale retail trade as control). Trials were performed on a completely randomized experimental design under artificial conditions with the release of males and females (ratio 1:3), at the most 24-h old. Among the assayed genotypes, the local one provided with a black coat (Grumo Appula Black) was significantly (P<0.05) the least susceptible to the cowpea beetle owing to the least number of laid eggs (2.0±1.8 under free-choice and 2.2±1.3 under no-choice bioassays), the delayed median developmental time (30.3±0.6 and 32.3±0.6, respectively), the lower adult emergence (45.6 and 46.2, respectively) and susceptibility index (7.7±2.04 and 7.8±0.51, respectively)

Suoli contaminati da As: l’importanza di speciazione e biodisponibilità per la valutazione del rischio reale

Qual è il rischio per la salute umana nell‟impiego di suoli contaminati da arsenico (As) in agricoltura o per il pascolo? Come è noto, non è tanto la concentrazione totale del contaminante a costituire di per sé una minaccia, quanto la sua distribuzione nelle diverse forme chimiche (speciazione), che ne influenza la frazione biodisponibile e quindi le sue possibilità di entrare nella filiera alimentare. E‟ in questa direzione che si muove il presente lavoro, volto a determinare il rischio reale che deriva dalla presenza di As in suoli campionati in aree pertinenti ad ex attività industriali (Scarlino, GR) e minerarie (Valle Anzasca, VB), con concentrazioni tra le decine ad alcune migliaia di ppm. È così stato adottato un duplice approccio, mirato ad ottenere da un lato una puntuale caratterizzazione chimico-mineralogica dei suoli stessi e quindi informazioni circa la speciazione dell‟As, dall‟altro a valutarne la biodisponibilità e l‟ecotossicità. Le analisi chimiche e mineralogiche dei suoli sono effettuate mediante tecniche che impiegano radiazione X; in particolare la caratterizzazione chimica in situ viene condotta tramite spettrometria di fluorescenza portatile con rivelatore a dispersione di energia (ED-pXRF), e in laboratorio mediante dispersione di lunghezza d‟onda (WD-XRF). In via preliminare esse hanno permesso di individuare nei suoli di Valle Anzasca una certa correlazione tre le concentrazioni rispettivamente di As e Fe e di As e S. La caratterizzazione mineralogica è invece condotta con un diffrattometro di raggi X su polvere (XRPD), introducendo corindone (Al2O3) come standard interno per la quantitativa. Non sono stati però rivelati minerali dell‟As, per via della loro scarsa concentrazione. Anche a questo proposito, sono in atto procedure di estrazione sequenziale (metodo Wenzel), per valutare la maggiore o minore mobilità dell‟As, ma pure ottenere informazioni complementari circa i minerali dell‟As presenti (ad esempio è stato individuato pentossido di As in un campione di Scarlino). Ulteriori dati circa la distribuzione dell‟As nei suoli vengono ottenuti per mezzo di una microfluorescenza di raggi X (ED-μXRF), effettuando scansioni dei suoli in sezione sottile. La biodisponibilità viene valutata utilizzando lombrichi epigeici della specie Eisenia andrei (Bouché), esposti a microcosmi contaminati e sottoposti ad analisi dei fluidi celomatici mediante TXRF e della distribuzione dell‟elemento nel corpo mediante ED-μXRF

TXRF analysis of earthworm coelomic fluid extracts: a useful tool to assess the bioavailability of As in soils

Arsenic (As) is a metalloid often associated to mining and industrial sites and its presence can cause health problems to living organisms and human beings. In order to assess As bioavailability in soils, tests which use earthworms as sentinel organisms are usually done. The evaluation of As concentration in the earthworm is commonly done after the whole digestion of the organism, which can lead to the overestimation of the concentration due to the possible presence of soil residues in the intestine. However, As is mainly accumulated by earthworms in the coelomic cavity , in particular in the coelomic fluid. This fluid can be easily extracted without killing the organism and analysed. Due to its small amount (less than 100 microliters), total x-ray fluorescence spectroscopy (TXRF) has demonstrated to be a powerful method for As detection in coelomic fluid extracts [1]. For these reasons, the present work aims at developing a new method to assess As bioavailability in contaminated soils by analyzing the As concentration in coelomic fluid extracts with TXRF. Six natural As polluted soils and two control soils were characterized by XRPD and WDXRF, while the As mobility was assessed by a sequential extraction procedure. Then, 10 sexually mature earthworms were exposed to each soil for 14 days. The elemental distribution inside the earthworm was studied by μXRF on thin sections, which localized As only in the coelomic cavity. After 24h without nourishment, three earthworms per soil were washed with distilled water and coelomic fluid extracts were collected from each of them applying a voltage of 5 V for 3 seconds. Ten microliters of extract were mixed with 80 µl of PVA and 10 µl of Y standard solution (10 mg/l). In order to compare the As concentration in the coelomic fluid extracts with the As concentration in the earthworm body, additional three earthworms per soil were depurated, dryed at 60 °C and pulverized. Slurry suspensionswere prepared using 100 mg of powder, 5 ml of Triton X-100 and 10 µl of Y standard solution (1000 mg/l). In both cases, 10 µl of sample were pipetted onto a quartz reflector and were left drying at 50 °C. TXRF analysis were performed with a S2 Picofox spectrometer (Bruker) using an acquisition time of 1000 s. Results revealed that As (both in fluids and whole bodies) increased with increasing mobile As in the soil. hHowever, As saturation (in both fluid and body) was observed when the mobile As fraction exceeded 200 mg/kg. Finally, the As concentration in coelomic fluids was positively correlated with that in the whole body. These results show that TXRF is a powerful tool to determine As concentration in earthworm coelomic fluids and that it can be used for As bioavailbility studies in soils. [1] I. Allegretta, C. Porfido, O. Panzarino, M.C. Fontanella, G.M. Beone, M. Spagnuolo, R. Terzano, Spectrochimica Acta Part B 130, 2017, 21-25

Combined biological assays and X-ray spectroscopy techniques to assess the bioavailability of arsenic in two industrial contaminated soils

Arsenic (As) is a metalloid, naturally associated with gold, sulphur, iron and heavy metals and is often found in soils and wastes around former mines and industrial sites because of the processing of As-bare minerals. Assessment of the bioavailability of As in these soils is very important in order to protect human and ecosystems health. Earthworms are often used to assess the bioavailability of As in soils (Langdon et al., 2003). In this work, Eisenia andrei was exposed to As-polluted soils from Valle Anzasca and Scarlino (Italy) in order to evaluate the bioavailability of As. Different X-ray based techniques were used to evaluate the concentration and the distribution of As both in soils and earthworms. For this study, three soil samples per polluted site were collected, sieved (2 mm) and dried. The mineralogical characterization of the soils was carried out by X-ray powder diffraction (XRPD). The total As was estimated on site via portable X-ray fluorescence (XRF), while sequential extractions (Wenzel et al., 2001) coupled with total reflection XRF (TXRF) were used to study the mobility of As. Soil elemental maps were acquired using micro XRF (µXRF) in order to evaluate the As distribution and its correlation with other elements. All the above analyses were conducted also on two control soils. For the assessment of the bioavailability, ten sexually mature earthworms were exposed to each contaminated soil and controls. The mortality was assessed after 14 days of exposure (acute toxicity). Oxidative stress was estimated by mesauring H2O2, catalase, phenoloxidase, glutathione S-transferase and malondialdehyde. The effect of As on the reproduction (chronic toxicity), was assessed after 28 days of exposure. Earthworms were embedded in epoxidic resin and thin sections (100 μm thickness) were analyzed via μXRF in order to localize As accumulation. Since detoxification mechanisms seem to act mainly inside the coelom (e.g. for Cd, Panzarino et al., 2016), coelomic fluids (few µl) were electrically extruded from worms and analysed by TXRF in order to quantify the As concentration...