Abitazione contadina e cultura materiale

Il contributo presenta lo stato degli studi sull'edilizia rurale tra alto e basso medioevo, incrociando testimonianze di fonti scritte, archeologiche, artistiche e etnografiche

Civiltà del legno: il monastero

none1noThe contribution would like to offer some reflections on use of wood in the monastic building structures, considering both written and archaeological sources. Attention is particularly directed to the articulation of the monastic space, to constructive activities and to material culture.openGaletti, PaolaGaletti, Paol

La forza delle acque: i mulini nell'Italia medievale

Il contributo esamina la diffusione dei mulini ad acqua nell'Italia medievale, cercando di delinearne lo sviluppo storico e la realtà materiale e tecnologica. Viene presentato inoltre un bilancio sulle principali linee di studio su questa tematica, sia sul versante della storia economico-sociale sia su quello della storia della tecnologia, sottolineando in primo luogo la dimensione locale della ricerca. Una riflessione è dedicata in secondo luogo alle fonti utili per impostare le indagini, secondo una ottica interdisciplinare

The power of water: the history of mills in Italy during the Middle Ages

Il contributo esamina la diffusione dei mulini ad acqua nell'Italia medievale, cercando di delinearne lo sviluppo storico e la realtà materiale e tecnologica. Viene presentato inoltre un bilancio sulle principali linee di studio su questa tematica, sia sul versante della storia economico-sociale sia su quello della storia della tecnologia, sottolineando in primo luogo la dimensione locale della ricerca. Una riflessione è dedicata in secondo luogo alle fonti utili per impostare le indagini, secondo una ottica interdisciplinare.This paper examines the spread of water mills in Italy during the Middle Ages, trying to define its historical development and the technology and the architecture. This study also includes an analysis of the different research approaches from the social-economic history to technology that are being pursued on this topic and it shows the development of a local dimension of the research. This paper also discusses which sources can be considered more suitable for the research of these topics and underlines the importance of an inter-disciplinary approach

Presupuestos sensibles al género en el marco de la cooperación UE-AL. Un estudio internacional comparado

Los presupuestos sensibles al género han sido impulsados en diversos países con el fin de reducir brechas de género al distribuir y orientar de manera más adecuada y equitativa los fondos públicos. Si bien las primeras experiencias datan de la década del 80, la Declaración y Plataforma para la Acción de Beijing adoptadas en septiembre de 1995 en el marco de Naciones Unidas, representó un punto de inflexión para el avance de este tipo de medidas dado que se instó explícitamente a los Estados a adoptar la perspectiva de género en el ámbito presupuestario. El presente trabajo pretende realizar una contribución al estudio de los presupuestos sensibles al género, en particular analizando las experiencias de Argentina, Brasil, Estado de Guanajuato y COSEFIN, y la contribución del programa Eurosocial, financiado por la Unión Europea. De esta manera, se busca conocer cómo se ha desarrollado el proceso de implementación de tales presupuestos en el contexto referido. El valor de esta investigación radica en que se pone el foco de atención en dicho proceso, a partir del análisis de la información documental existente en los archivos de las instituciones estudiadas y de la recogida de datos primarios a través del desarrollo de entrevistas a las personas expertas que han tenido un importante rol en las iniciativas.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Metabolism of the EGFR tyrosin kinase inhibitor gefitinib by cytochrome P450 1A1 enzyme in EGFR-wild type non small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) especially effective in tumors with activating EGFR gene mutations while EGFR wild-type non small cell lung cancer (NSCLC) patients at present do not benefit from this treatment.</p> <p>The primary site of gefitinib metabolism is the liver, nevertheless tumor cell metabolism can significantly affect treatment effectiveness.</p> <p>Results</p> <p>In this study, we investigated the intracellular metabolism of gefitinib in a panel of EGFR wild-type gefitinib-sensitive and -resistant NSCLC cell lines, assessing the role of cytochrome P450 1A1 (CYP1A1) inhibition on gefitinib efficacy. Our results indicate that there is a significant difference in drug metabolism between gefitinib-sensitive and -resistant cell lines. Unexpectedly, only sensitive cells metabolized gefitinib, producing metabolites which were detected both inside and outside the cells. As a consequence of gefitinib metabolism, the intracellular level of gefitinib was markedly reduced after 12-24 h of treatment. Consistent with this observation, RT-PCR analysis and EROD assay showed that mRNA and activity of CYP1A1 were present at significant levels and were induced by gefitinib only in sensitive cells. Gefitinib metabolism was elevated in crowded cells, stimulated by exposure to cigarette smoke extract and prevented by hypoxic condition. It is worth noting that the metabolism of gefitinib in the sensitive cells is a consequence and not the cause of drug responsiveness, indeed treatment with a CYP1A1 inhibitor increased the efficacy of the drug because it prevented the fall in intracellular gefitinib level and significantly enhanced the inhibition of EGFR autophosphorylation, MAPK and PI3K/AKT/mTOR signalling pathways and cell proliferation.</p> <p>Conclusion</p> <p>Our findings suggest that gefitinib metabolism in lung cancer cells, elicited by CYP1A1 activity, might represent an early assessment of gefitinib responsiveness in NSCLC cells lacking activating mutations. On the other hand, in metabolizing cells, the inhibition of CYP1A1 might lead to increased local exposure to the active drug and thus increase gefitinib potency.</p

Epidermal Growth Factor Receptor Intron-1 Polymorphism Predicts Gefitinib Outcome in Advanced Non-small Cell Lung Cancer

IntroductionEpidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC).MethodsBlood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied.ResultsEGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003).ConclusionsThis study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC

Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.

Glomerular planted antigens (histones,DNA,andC1q) arepotential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patientswith LN. Prevalent antibody isotypes were defined, levelswere determined, and glomerular colocalization was investigated. Renal and circulating antibodieswerematched, and serum levelswere compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (antia-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti a-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and antia-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria.3.5 g/24 hours and creatinine&gt;1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis

Glomerular autoimmune multicomponents of human lupus nephritis in vivo: α-enolase and annexin AI

Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens in renal biopsy samples from patients with LN and determine whether the same autoantibodies can be detected in circulation. Glomeruli were microdissected from biopsy samples of 20 patients with LN and characterized by proteomic techniques. Serum samples from large cohorts of patients with systemic lupus erythematosus (SLE) with and without LN and other glomerulonephritides were tested. Glomerular IgGs recognized 11 podocyte antigens, with reactivity varying by LN pathology. Notably, IgG2 autoantibodies against α-enolase and annexin AI were detected in 11 and 10 of the biopsy samples, respectively, and predominated over other autoantibodies. Immunohistochemistry revealed colocalization of α-enolase or annexin AI with IgG2 in glomeruli. High levels of serum anti-α-enolase (>15 mg/L) IgG2 and/or anti-annexin AI (>2.7 mg/L) IgG2 were detected in most patients with LN but not patients with other glomerulonephritides, and they identified two cohorts: patients with high anti-α-enolase/low anti-annexin AI IgG2 and patients with low anti-α-enolase/high anti-annexin AI IgG2. Serum levels of both autoantibodies decreased significantly after 12 months of therapy for LN. Anti-α-enolase IgG2 recognized specific epitopes of α-enolase and did not cross-react with dsDNA. Furthermore, nephritogenic monoclonal IgG2 (clone H147) derived from lupus-prone MRL-lpr/lpr mice recognized human α-enolase, suggesting homology between animal models and human LN. These data show a multiantibody composition in LN, where IgG2 autoantibodies against α-enolase and annexin AI predominate in the glomerulus and can be detected in serum