LA RIDUZIONE DEI MACROFAGI CD68+ TISSUTALI E LA DIMINUZIONE NELL'ESPRESSIONE MUCOSALE DI INTERLEUCHINA 17 SONO STRETTAMENTE CORRELATI CON LA RISPOSTA ENDOSCOPICA E CON LA GUARIGIONE DELLA MUCOSA A SEGUITO DI TERAPIA CON INFLIXIMAB IN PAZIENTI CON MALATTIE INFIAMMATORIE CRONICHE INTESTINALI

Background: Antibodies against tumor necrosis factor represent an effective therapy for patients with inflammatory bowel disease. Despite their successful results, the exact mechanism by which infliximab suppresses intestinal inflammation is still a matter of debate. In this study, we used a translational approach to identify the key mechanisms associated with resolution of mucosal inflammation induced by infliximab. Methods: A total of 16 patients with active inflammatory bowel disease (9 with Crohn\u2019s disease and 7 with ulcerative colitis) and 13 controls were enrolled in the study. Patients received infliximab infusions at 0, 2, and 6 weeks. At enrollment and at week 6, patients underwent flexible sigmoidoscopy, and biopsies were taken from the sigmoid colon. RNA was extracted, and mucosal expression of 96 immune-related genes was evaluated by qRT-PCR and confirmed by immunofluorescence microscopy on tissue. Correlation between infliximab-induced gene expression modulation and endoscopic response to therapy was calculated. Lamina propria mononuclear cell apoptosis induced by infliximab was evaluated on tissue sections by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: We found that infliximab-induced downregulation of macrophage and Th17 pathway genes was significantly associated with both endoscopic response to the therapy and achievement of mucosal healing. Importantly, the observed reduction of lamina propria CD68+ macrophages was associated with an increased rate of macrophage apoptosis. Conclusions: The 2 mechanisms associated with infliximab-induced resolution of intestinal inflammation are the reduction of lamina propria infiltrating CD68+ macrophages and the downregulation of interleukin 17A. Moreover, the data suggest that infliximab-induced macrophage apoptosis may represent a key mechanism for the therapeutic success of anti\u2013tumor necrosis factor antibodies

A wait-and-watch approach to small pancreatic neuroendocrine tumors : Prognosis and survival

Background: Whether all the small (\u3c6 6420mm) non-functional pancreatic neuroendocrine neoplasms (pNENs) should be routinely resected is unclear. Aim: To assess the overall survival (OS) and progression-free survival (PFS) of patients with small pNENs, followed-up with different management options. Material and methods: Between 2007-2014, 51 patients were newly diagnosed with pNEN. 15 patients with pNENs \u3c6 6420 mm underwent an intensive follow-up at 3-month intervals during the first year and then every 6 months (FU pNEN group). They were all at TNM stage I, except for one patient at stage IIA. 21 patients underwent surgical resection (SR pNEN group): 2 patients were at TNM stage I, 9 IIA, one IIIB, 9 IV. 15 patients received systemic therapy (ST pNEN group) due to advanced disease or contraindications to surgery: 5 were at stage IIA, 2 IIB, 8 IV. Results: The median follow-up for the entire cohort was 50 months. Survival was similar in the FU and SR pNEN groups, but significantly worst in the ST pNEN patients (log-rank test P < 0.05). The 4-year survival rate was 100% in the FU pNEN group, 90.5% among the SR pNEN patients, 61% for the ST pNEN ones (p < 0.0001). The disease remained stable in all but one patient in the FU pNEN group, whereas six patients in the SR group and five in the ST group showed disease progression. Conclusions: The "wait-and-watch" approach to early-stage small pNENs appears to be safe although further studies are needed to confirm these results in larger cohorts of patients

Multiparametric seafloor exploration: the Marsili Basin and Volcanic Seamount case (Tyrrhenian Sea, Italy)

Exploration of ocean seafloor is of paramount importance for a better understanding of the geodynamic evolution of our Planet. The pilot experiment of ORION-GEOSTAR 3 EC project was the first long-term continuous geophysical and oceanographic experiment of an important seafloor area of Southern Tyrrhenian Sea, the Marsili abyssal plain. The latter hosts the Marsili Seamount which is Europe’s one of the largest underwater volcano of Plio-Pleistocenic age. In spite of its dimensions, it is rather unknown about the present characteristics and activity. For this reason, we deployed a deep-sea observatory network, composed by two bottom observatories, on the seafloor at the base of the seamount at 3320 m b.s.l., in the period December 2003-May 2005. Some of the instruments on board the observatory were: broad-band seismometers, hydrophones, gravity meter, two magnetometers (scalar and vectorial), 3D single-point current meter, ADCP, CTD, automatic pH analyser and off-line water sampler for laboratory analyses. The first successful scientific objective was to obtain long-term continuous recordings under a unique time reference. The data analysis shows that they are generally of good quality and really continuous (only a few gaps). As a first step we performed a classification of seismic waveforms, a first inversion of magnetic variational data, and a first analysis of gravity meter, chemical and oceanographic data. Analysis of individual time series has shown interesting results, i.e. depth of the magnetic Moho under the Marsili, attenuation of recorded seismic body waves and clues of hydrothermal circulation. We show examples of the preliminary data analysis together with first results and comparisons among data coming from different sensors.PublishedCambridge, UK, February 24-26, 20091.8. Osservazioni di geofisica ambientale3.8. Geofisica per l'ambienteope

Multiparametric seafloor exploration: the Marsili Basin and Volcanic Seamount case (Tyrrhenian Sea, Italy)

Exploration of ocean seafloor is of paramount importance for a better understanding of the geodynamic evolution of our Planet. The pilot experiment of ORION-GEOSTAR 3 EC project was the first long-term continuous geophysical and oceanographic experiment of an important seafloor area of Southern Tyrrhenian Sea, the Marsili abyssal plain. The latter hosts the Marsili Seamount which is Europe’s one of the largest underwater volcano of Plio-Pleistocenic age. In spite of its dimensions, it is rather unknown about the present characteristics and activity. For this reason, we deployed a deep-sea observatory network, composed by two bottom observatories, on the seafloor at the base of the seamount at 3320 m b.s.l., in the period December 2003-May 2005. Some of the instruments on board the observatory were: broad-band seismometers, hydrophones, gravity meter, two magnetometers (scalar and vectorial), 3D single-point current meter, ADCP, CTD, automatic pH analyser and off-line water sampler for laboratory analyses. The first successful scientific objective was to obtain long-term continuous recordings under a unique time reference. The data analysis shows that they are generally of good quality and really continuous (only a few gaps). As a first step we performed a classification of seismic waveforms, a first inversion of magnetic variational data, and a first analysis of gravity meter, chemical and oceanographic data. Analysis of individual time series has shown interesting results, i.e. depth of the magnetic Moho under the Marsili, attenuation of recorded seismic body waves and clues of hydrothermal circulation. We show examples of the preliminary data analysis together with first results and comparisons among data coming from different sensors

Efecto de la aireación y la concentración de cloruro sódico en el desarrollo de la flora microbiológica y en los parámetros fisicoquímicos en la fermentación de <i>Olea europaea</i> L. c.v. Sevillana al estilo negras naturales en la zona de La Yarada-Tacna

The aerobic fermentation of the table olive variety, Sevillana a black style, was carried out, taking into account the parameters of fermentation of fixed acidity between 1.2 to 1.5% and depended on the chloride concentration in the brine. This concentration was under 6.5% in the 9 treatments assayed, allowing for the lactic bacteria to develop. In the aerobic fermentation there were no differences in the decline of pH in relation to the anaerobic fermentation, which reached values below 3.5. The air effect is of great significance in the purge of the carbon dioxide in the brine. At the same time, the effect of air significantly affects the increase in aerobic yeast. The facultative anaerobic yeasts developed in the treatments with an initial salt level of 12% at the beginning of fermentation. The reduction of sugar concentration into the fruit decreased significantly in the treatment with air. Aerobic fermentation is more rapid than anaerobic fermentation.<br><br>La fermentación aerobia de aceituna variedad Sevillana estilo negra se desarrolló en los parámetros de acidez fija entre de 1.2 a 1.5%, debido a la concentración de cloruros en la salmuera los cuales se mantuvieron por debajo de 6.5% durante el periodo de fermentación en los 9 tratamientos ensayados lo que permitió el desarrollo de bacterias lácticas. No hubo diferencia en la evolución del pH entre la fermentación con aireación o en condiciones anaeróbicas alcanzándose valores menores a 3.5. La aireación tiene un efecto significativo en la purga del CO₂ en la salmuera e incrementó la población de levaduras aerobias; así mismo en los tratamientos con 12% de sal se favoreció el desarrollo de levaduras fermentativas al inicio de la fermentación. La concentración de azúcares reductores en el fruto disminuyó significativamente en los tratamientos con aireación, acelerando el proceso de fermentación con respecto a la fermentación anaerobia

Proteome Regulation during Olea europaea Fruit Development

Widespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes.In this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies.This study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process