Effects of cholera toxin on cells of immune system

In questa tesi sono stati analizzati gli effetti della Tossina Colerica (CT) sulle cellule del sistema immunitario. In particolare, sono stati studiati i meccanismi di inibizione della proliferazione dei linfociti T CD4+ e CD8+ umani da parte della CT. E’ stato osservato che la CT è in grado di prevenire l’attivazione dei linfociti T nelle fasi precoci e tale inibizione coinvolge la modulazione dell’espressione delle molecole CTLA-4 e CD28. E’ stato osservato che la CT up-regola l’espressione delle molecole inibitorie CTLA-4 e down-modula le molecole costimolatorie CD28 sui linfociti T CD4+ e CD8+ resting. L’incremento dell’espressione delle molecole CTLA-4 da parte della CT gioca un ruolo nel controllare l’attivazione e la proliferazione dei linfociti T, infatti, abbiamo osservato che anticorpi bloccanti anti-CTLA-4 F(ab’)2 sono in grado di prevenire, anche se parzialmente, tale inibizione. I nostri studi hanno valutato, inoltre, la funzione di linfociti T pre-trattati con la CT e abbiamo osservato che essi sono in grado di inibire la proliferazione di linfociti T autologhi stimolati con anti-CD3. Abbiamo inoltre osservato che questo fenomeno è mediato dal rilascio di cAMP all’esterno delle cellule. Alla luce di questi risultati, abbiamo analizzato gli effetti esercitati dall’cAMP extracellulare come primo messaggero su diversi tipi cellulari. L’cAMP extracellulare è in grado di inibire la proliferazione dei linfociti T ed è in grado di interferire con il differenziamento dei monociti in cellule dendritiche (DCs). Infatti, monociti differenziati in presenza di cAMP esogeno, non esprimono molecole CD1a e mantengono l’espressione di molecole CD14, acquisendo un fenotipo simile ai macrofagi. Tuttavia, le cellule generate in presenza di cAMP esogeno esprimono alti livelli di molecole MHC di classe II e di classe I e molecole costimolatorie CD86, mostrando un fenotipo attivato in grado di stimolare risposte T allogeniche. Inoltre, tali cellule non sono in grado di produrre TNF-α e IL-12, ma rilasciano quantità elevate di IL-6 e di IL-10. Monociti trattati con cAMP extracellulare hanno una capacità ridotta di indurre il differenziamento di linfociti T CD4+ che producono IFN-γ. Infine, è stato investigato il meccanismo attraverso il quale il cAMP extracellulare interagisce con le cellule. Utilizzando diversi antagonisti dei recettori dell’adenosina, abbiamo osservato che gli effetti mediati dal cAMP extracellulare possono essere prevenuti. Tali risultati suggeriscono che l’cAMP sia trasformato in adenosina e che tale molecola, attraverso l’interazione con i suoi recettori, sia responsabile degli effetti mediati dal cAMP esogeno.In this study, we analysed the effects of Cholera Toxin (CT) on cells of immune system. In particular, the mechanisms underling the inhibition of T cell proliferation mediated by CT on human CD4+ and CD8+ T lymphocytes were analysed. We observed that CT prevents the early activation steps of T lymphocytes and that these effects involve the modulation of costimulatory molecules CTLA-4 and CD28. We observed that CT up-regulates the expression of the inhibitory molecule CTLA-4 in resting CD4+ and CD8+ T lymphocytes. The regulation of CTLA-4 expression by CT is at the transcriptional level. Indeed, in cells treated with CT we observed an increase of two mRNA variants coding for the membrane and the soluble CTLA-4 molecules. In parallel with the up-regulation of the inhibitory molecule CTLA-4, CT down-modulates the costimulatory molecule CD28 on CD4+ and CD8+ resting T cells. The increased expression of CTLA-4 plays a role in controlling T cell activation and function as blocking anti-CTLA-4 F(ab’)2 mAbs partially prevents the inhibition mediated by CT. We evaluated the function of CT-pre-treated CD4+ T lymphocytes and we observed that they are able to inhibit the proliferation of autologous T lymphocytes stimulated with anti-CD3 mAbs. It is interesting that this phenomenon is, at least in part, a result of the release of extracellular cAMP. Therefore, by analysing the direct effects exerted by extracellular cAMP as a primary messenger on different cell types, we found that extracellular cAMP inhibits T cell proliferation and that it is able to interfere with the differentiation of monocytes into DCs. Monocytes induced to differentiated into DCs in the presence of extracellular cAMP, do not express CD1a molecules and retain the expression of CD14 acquiring a macrophages-like phenotype. Furthermore, they strongly up-regulate MHC class I and class II and CD86 costimulatory molecules giving rise to an activated population able to stimulate allogeneic T cell response. In addition, they produce a distinct pattern of cytokines upon maturation stimuli, they are unable to produce TNFα and IL-12 and they release high amount of IL-6 and IL-10. Furthermore, monocytes differentiated in the presence of cAMP show a reduced capacity of inducing the differentiation of IFNγ producing CD4+ T lymphocytes. Finally, the mechanisms through which extracellular cAMP can be sensed by the cells were studied. By using different adenosine receptors antagonists, we found that an extracellular cAMP-adenosine pathway is involved in the effects mediated by exogenous cAMP, suggesting that extracellular cAMP acting as primary messenger can be sensed by the cells of immune system and can modulate their functions

Use of clinoptilolite in piglet diets as a substitute for Colistine

The effects of adding 2% of natural zeolite, containing a high percentage of clinoptilolite, to the diet of piglets was eval- uated by monitoring growing performance and plasma parameters. The diet was also deprived of Colistine, an antibiotic usually added to piglet diets at subtherapeutic levels to prevent gastrointestinal pathology. Sixty-four piglets, weaned at 7.9 kg live weight, were divided in 2 groups of 32 each. The control group was given commercial piglet feedstuffs; for the treated group, 98% of the same feed, deprived of Colistine, was used, with the addition of 2% of a natural zeolite. The trial lasted 36 days. The piglets fed the control diet exhibited greater weight in the first three weeks, after which the differences were not significant. The average daily weight gain in the first week was higher in the control group (+37%; P<0.01) whereas at the end of the trial no differences were found. The feed intake did not show significant differences between groups and, as a result, the Feed Efficiency at the end of the trial was higher in the control group (532 vs. 491, P< 0.05). The plasmatic nitrogen parameters did not show significant differences between groups. Only in the first three weeks post-weaning the group fed the diet containing Colistine showed better ADG, subsequently it can be eliminated and clinoptilolite could favour growth

Palazzo di Giustizia : costituzione di consorzio fra i comuni del distretto giudiziario di Salerno

Estratto dal protocollo delle deliberazioni commissariali, n.34 (14 maggio 1929). - Piano di ammortament

Desarrollo del pensamiento estadistico en un curso de didáctica de la estadística. El caso de una profesora en formación

la creciente necesidad de analizar gran cantidad de información en la sociedad, ha llevado a que la Estadística se convierta en una disciplina de vital importancia para todos los ciudadanos. Esto también ha repercutido en diversos sistemas educativos, los currículos de Matemática (NCTM, 2000; MINEDUC, 2015) y en el profesorado, tanto en formación como en ejercicio. Diversas han sido las propuestas para promover y potenciar la enseñanza de la Estadística (Pfannkuch, 2006; Estrella, 2017), la cual ha sido compleja dado el carácter que tiene esta disciplina en tanto que debe promover aspectos que van más allá de lo procedimental, es decir, hacer énfasis en las interpretaciones, profundizar en la enseñanza de las conceptualizaciones, conocimiento de contexto, promover la idea de incertidumbre y variabilidad (Makar y Rubin, 2009). Lo anterior es fundamental, si lo que se pretende es que los estudiantes en contexto escolar conozcan los rudimentos que subyacen a la Estadística, pero para ello es necesario que los profesores que enseñan estadística, también conozcan estos aspectos y sean quienes desarrollen procesos de profundización en el aprendizaje de la Estadística. Dado lo anterior, en este trabajo (en proceso), buscamos explorar si una profesora de Matemática en formación desarrolla ideas de Pensamiento Estadístico con base en algunas actividades adaptadas de libros de texto especialmente para tal fin

Genotoxic activity of the Fumonisin B1 mycotoxin in cultures of bovine lymphocytes

The fumonisins, produced by fungi that infest foodstuffs, in particular corn, are responsible for a series of illnesses and toxicosis in various species of animals, including humans. There is still not detailed information about the genotoxic and mutagenic activity of Fumonisin B1 (FB1), but it is clear that it interferes with growth control, differentiation and cellu- lar apoptosis. The purpose of this study was to assess the genotoxic potential of Fumonisin B1 using in vitrocultures of bovine lymphocytes, through the calculation of the ‘mitotic index’ (MI), the frequency of ‘sister chromatid exchange’ (SCE) and the ‘micronucleus test’ (MN). The bovine lymphocytes were exposed to different concentrations of FB1 (25, 50 and 100 µM) in order to find out which amount is sufficient to cause a reduction in the mitotic potential of the cells, the onset of MN and a higher frequency of SCE. The results obtained show a considerable reduction in the ‘mitotic index’ with a FB1 concentration of 50 µM, an increase in the frequency of MN with a concentration of 50 µM and a significant increase in the SCE with a concentration of 100 µM. In the light of the information we have obtained, compared with that of other Authors, we feel that the genotoxic poten- tial of FB1 has been underestimated until now and should, therefore, be reconsidered

“Soy un papá súper normal”: Experiencias parentales de hombres gay en Chile

Las identidades de ‘padre’ y ‘homosexual’ suelen verse como mutuamente excluyentes. El propósito de este artículo es explorar las experiencias de paternidad de hombres homosexuales en Chile. Se realizaron entrevistas en profundidad a 14 padres que se auto identifican como homosexuales o gay y que han tenido hijos tanto en el marco de una relación heterosexual, como en el contexto de una relación homosexual (a través de gestación subrogada o acuerdo de coparentalidad). Los resultados muestran que las experiencias de paternidad de los padres gay no son muy diferentes a las de los padres heterosexuales. Las diferencias estriban en que los padres homosexuales a) desafían estereotipos culturales que asumen que una mujer es necesaria para criar un/a niño/a y b) desarrollan estrategias para proteger a sus familias de un entorno hostil. En este artículo mostramos cómo un contexto heteronormativo que devalúa a la homosexualidad influye en las experiencias parentales de hombres gay en Chile.The identities of father and homosexual can be seen as mutually exclusive. The purpose of this paper is to explore how gay men in Chile experience parenting. In-depth interviews were conducted with fourteen men who self-identified as homosexual and had become fathers in a previous heterosexual relationship or with a same-sex partner (through gestational surrogacy or a co-parenting agreement). The results show that gay fatherhood is not essentially different from heterosexual fatherhood. Two main differences were identified: a) homosexual fathers challenge cultural stereotypes that assume that a woman is necessary to raise a child and b) they develop strategies to protect their families from a hostile social environment. A heteronormative context that devaluates homosexuality directly influences the parenting experiences of gay men in Chile.As identidades de 'pai' e 'homossexual' tendem a ser vistas como mutuamente excludentes. O objetivo deste artigo é explorar as experiências de paternidade de homens homossexuais no Chile. Foram realizadas entrevistas em profundidade a 14 pais que se identificam como homossexuais ou gay e que tiveram filhos tanto no contexto de uma relação heterossexual, quanto no contexto de uma relação homossexual (através de barrigas de aluguel ou acordo de co-parentalidade). Os resultados mostram que a paternidade gay não é essencialmente diferente da paternidade heterossexual. As diferenças são que os pais homossexuais a) desafiam estereótipos culturais que pressupõem que uma mulher é necessária para criar um filho e b) desenvolvem estratégias para proteger suas famílias num ambiente hostil. Neste artigo, mostramos como um contexto heteronormativo que desvaloriza a homossexualidade influencia as experiências parentais de gays no Chile

Tasa de publicaciones científicas de resúmenes presentados en Congreso Nacional de Estudiantes de Odontología, Chile 2013-2017

Objective: To determine the rate of publication of abstracts presented at the National Congress of Dental Students (CONADEO) 2013-2017 and to analyze publications according to Institution of origin, study design, and journal indexing. Material and Methods: Descriptive cross-sectional study. The abstracts presented were sought in MEDLINE (PubMed), SciELO, and Google Scholar to locate their respective publications. Information was collected regarding the study design, institution of origin of the abstract, name of the journal, indexing, and impact factor. These data were registered in Google Forms and exported to Google Spreadsheets, to be analyzed using descriptive statistics. Results: 627 abstracts were included. The publication rate resulted in 1.75%.  The institution with the most publications was the Universidad de Talca (45.45%). The type of study design with most publications was Bibliographic reviews (45.45%). 54.54% of the publications located were indexed in other databases. Conclusions: The rate of publication of abstracts presented in CONADEO was found to be low compared to the number of abstracts presented. It is suggested further analysis to investigate the possible barriers that prevented achieving a final publication.Objetivo: Determinar la tasa de publicación de resúmenes presentados en el Congreso Nacional de Estudiantes de Odontología (CONADEO) 2013-2017 y analizar publicaciones según Institución, diseño de estudio e indexación de la revista.Material y Métodos: Estudio descriptivo transversal. Los resúmenes presentados fueron revisados en MEDLINE(PubMed), SciELO y Google Scholar, para localizar sus respectivas publicaciones. Se recopiló información acerca del diseño de estudio, institución del resúmen, nombre de la revista, indexación y factor de impacto. Estos datos fueron registrados en Google Forms y exportados a Google Sheets, para ser analizados mediante estadística descriptiva. Resultados: Se incluyeron 627 de los 632 resúmenes presentados. La tasa de publicación resultó ser de un 1,75%. La institución con más publicaciones fue la “Universidad de Talca” (45,45%). El diseño de estudio con más publicaciones fueron “Revisiones bibliográficas” (45,45%). Un 54,54% de las publicaciones fueron indexadas en “otras” bases de datos. Conclusión: La tasa de publicación de resúmenes presentados en CONADEO mostró ser baja en comparación con la cantidad de resúmenes que se presentan. Se sugiere que investigaciones futuras indaguen en las posibles barreras que impidieron llegar a una publicación final