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IN VITRO TOXICOLOGICAL EFFECTS OF FUMONISIN B1 ALONE AND COMBINED WITH OTHER MYCOTOXINS
Mycotoxins, secondary metabolites produced by moulds, mainly Aspergillus spp., Fusarium spp. and Penicillium spp., are common contaminants of food and feed. The aim of this project was to evaluate: (i) the potential endocrine disruptor effects of fumonisin B1 (FB1), beauvericin (BEA), deoxynivalenol (DON) and zearalenone (ZEA) metabolites �-zearalenol (�-ZEA) and �zearalenol (�ZEA), alone and combined, using a bovine granulosa cell (GC) in vitro model and (ii) the individual and combined effects of FB1 and BEA on the intestinal barrier using Caco-2 cells cultured in vitro on semipermeable inserts.
The results obtained indicated that FB1 alone at all tested doses (0; 0.5; 1; 1.5; 3; 6 �M) had no effects on GC proliferation and progesterone (P4) production. In the presence of �ZEA at30 ng/mL (0.094 �M), FB1 at 30 ng/mL (0.042 �M) showed a stimulatory effect on GC numbers. Cell proliferation decreased after exposure to �ZEA alone at 5.0 mg/mL (15.6 �M) and FB1 with �-ZEA and �ZEA at the same concentration. Regarding steroid production, FB1 at 30 ng/mL (0.042 �M ) and 100 ng/mL (0.13 �M amplified the inhibitory effect of �ZEA at 30 ng/mL (0.094 �M) on estradiol (E2) production, while FB1 alone increased (P<0.05) IGF1-induced E2 production. FB1 in combination with �ZEA decreased (P < 0.05) E2 production. FB1 at 1, 1.5 and 3 �M slightly inhibited (P < 0.05) E2 production. BEA at concentrations � 3 �M was found to strongly decrease (P < 0.05) both steroid production and FB1 did not influence the effects of BEA. At 10 �M both mycotoxins decreased (P < 0.001) serum-induced GC proliferation. At 30 �M, BEA showed inhibitory effects on FSH plus IGF-1-induced CYP11A1 and CYP19A1 mRNA abundance (P < 0.05), whereas FB1 at 30 �M had no effect on CYP11A1 and CYP19A1 gene expression.
As regards the effects of FB1 and BEA, alone and combined, on the Caco-2 intestinal barrier model data showed a TEER decrease after 1 h and 2 h of Bl exposure to BEA at 0.5 and 1.5 �M and after 24 h of Bl exposure to BEA at 0.5 �M, whereas after 24 h of Bl exposure, BEA at 3 and 6 �M was found to significantly (P < 0.05) increase TEER.
FB1 had no effect on the intestinal barrier integrity and when combined with BEA the TEER increase induced by BEA was no longer observed.
Cytokine release was observed only after exposure to BEA alone, and not in combination with FB1, with an increase of IL-6 and IL8 release after apical exposure to 3 and 6 �M and after basolateral exposure to 1.5, 3, 6 �M for IL-6 and only to 6 �M for IL-8. TNF- � release was induced by Ap (0.5 -1.5 �M) and Bl (1.5 �M) exposure to BEA.
Overall, these results provide information on in vitro toxicological effects of Fusarium mycotoxins
I determinanti della salute
Lo stato di salute di un individuo e – più estesamente – di una comunità o di una popolazione è influenzato, determinato da molteplici fattori. Lo studio dei determinanti della salute costituisce la base e la so- stanza della sanità pubblica, perché consente di analizzare (e possibilmente modificare) i fattori che in varia misura influenzano l’insorgenza e l’evoluzione delle malattie. Il modello (1), che presen- tiamo nella Figura 1, è espresso in una serie di stra- ti concentrici, corrisponden- ti ciascuno a differenti livelli di influenza. Al centro c’è l’individuo, con le sue caratteristiche biologiche: il genere, l’età, il patrimonio genetico. Lo strato successivo riguarda il comportamento, lo stile di vita degli indivi- dui, che includono fattori come l’abitudine al fumo e all’alcol, i comportamenti alimentari e sessuali, l’attività fisica, che possono promuovere o danneggiare la salute. Queste scelte – come vedremo in seguito – possono essere libere o condizionate. Ma l’individuo non esiste da solo: egli interagisce con i familiari, gli amici, la comunità circostante. Così la qualità degli affetti e delle relazioni sociali influenza la qualità della vita delle singole persone e può determinare un diverso sta- to di salute sia attraverso meccanismi psicologici (la depressione e l’ansia), che attraverso condizioni materiali favorevoli o avverse (es: la presenza o l’assenza di una rete di supporto fa- miliare o sociale). Il quarto livello concerne un insieme complesso di fattori che riguardano l’ambiente di vita e di la- voro delle persone: il reddito, l’occupazione, l’istruzione, l’alimentazione, l’abitazione, le condizioni igieniche, i trasporti e il traffico, i servizi sanitari e sociali. Lo strato più esterno si ri- ferisce alle condizioni generali – politiche, sociali, culturali, economiche, ambientali – in cui gli individui e le comunità vivono.
Di questa serie di determinanti, alcuni – le caratteristi- che biologiche dell’individuo (il sesso, l’età, il patrimonio genetico) – sono immodificabili, mentre tutti gli altri sono suscettibili di essere tra- sformati o corretti. Il destino di salute di una persona, di una comunità o di una popolazione dipende quindi da una molteplicità di situazioni e di livelli di responsabilità:
• la responsabilità indivi- duale circa i comportamenti e gli stili di vita;
• la responsabilità familiare o di gruppo circa le relazioni affettive e sociali;
• la responsabilità di una comunità o un governo lo- cale o nazionale circa le politiche sociali, del lavoro e dell’assetto del territorio (da cui dipende la disponibilità e accessibilità dei servizi sanitari, sociali ed educativi, l’occupazione, la fruibilità delle infrastrutture);
• la responsabilità infine dei soggetti sovranazionali – come Nazioni Unite, Organizzazione mondiale della sanità, Banca Mondiale, Fondo monetario interna- zionale, Organizzazione mondiale del commercio, etc. – che hanno il potere di regolare i rapporti tra gli Stati, tra gli Stati e le imprese economiche e finanziarie multinazionali, e di influenzare i meccanismi macroeconomici che sono alla base della ricchezza e dello sviluppo di alcuni, e della povertà e del sottosviluppo di altri
Effects of a fusarium mycotoxin, beauvericin, on bovine granulosa cell proliferation and steroid production
In vitro toxicity of beauvericin alone and combined with fumonisin B1 or deoxynivalenol on Caco-2 cells
Beauvericin (BEA) is a mycotoxin produced by Fusarium species, frequently occurring in cereal grains in combination with fumonisin B1 (FB1) and deoxynivalenol (DON). The aim of this study was to evaluate the in vitro toxic effects of BEA alone and combined with FB1 or DON on human intestinal Caco-2 cells cultured on semi-permeable inserts (Caloni et al., 2012). Caco-2 cells were treated for 24 h with BEA (1.5 μM) alone and combined with FB1 (1.5 μM) or DON (3.5 μM) on both apical (Ap) and basolateral (Bl) sides. Barrier impairment was assessed by measuring the trans-epithelial electrical resistance (TEER) after 1 h, 2 h and 24 h of treatment. At the end of the experiment, the culture medium was collected for interleukin-8 (IL-8) determination. The results indicate that TEER was not significantly affected by Ap or Bl exposure to BEA and FB1 alone, whereas a significant decrease (P<0.05) of TEER was observed after exposure to BEA in combination with FB1 for 1 h and 2 h. DON was found to decrease (P<0.05) TEER alone and combined with BEA after Bl application starting from the second hour of treatment. No significant release of the inflammatory mediator IL-8 was observed after Ap or Bl exposure to BEA and FB1 alone and in combination. On the contrary, DON alone and combined with BEA induced a significant (P<0.05) release of IL-8 after both Ap and Bl exposure. Further investigations are underway to better clarify the effects of BEA on the intestinal epithelium and its interaction with other fusariotoxins
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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