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pregnane X receptor and constitutive androstane receptor modulate differently CYp3A-mediated metabolism in earlyand late-stage cholestasis

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World Journal of Gastroenterology 2017年第42期23卷 7519-7530页

作者： Daniela Gabbia Arianna Dalla Pozza Laura Albertoni Roberta Lazzari Giorgia Zigiotto maria carrara Vincenzo Baldo Tatjana Baldovin Annarosa Floreani Sara De Martin Department of Pharmaceutical and Pharmacological Sciences University of Padova Department of Medicine General Pathology and Cytopathology UnitUniversity of Padova Department of Cardiac Thoracicand Vascular SciencesHygiene and Public Health UnitUniversity of Padova Department of Surgery Oncology and GastroenterologyUniversity of Padova

AIM To ascertain whether cholestasis affects the expression of two CYP3 A isoforms(CYP3 A1 and CYP3 A2) and of pregnane X receptor(PXR) and constitutive androstane receptor(CAR).METHODS Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3 A1 and CYP3 A2 were assessed by means of q RT-PCR and Western blot, respectively. Alterations in CYP3 A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3 A enzymes.RESULTS The m RNA and protein expression of CYP3 A1 increased significantly in mild cholestasis(P < 0.01). At variance, m RNA and protein expression of CYP3 A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3 A1 and CYP3 A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR.CONCLUSION Early-and late-stage cholestasis affects CYP3 Amediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3 Amediated liver detoxification.

关键词： Cholestasis CYP3A Drug metabolism Pregnane X receptor Constitutive androstane receptor

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Quantifying water stress effect on daily light use efficiency in Mediterranean ecosystems using satellite data

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International Journal of Digital Earth 2017年第6期10卷 623-638页

作者： Sergio Sanchez-Ruiz Alvaro Moreno maria Piles Fabio Maselli Arnaud carrara Steven Running maria Amparo Gilabert Departament de Fisica de la Terra i Termodinamica Facultat de FisicaUniversitat de ValenciaBurjassotSpain Numerical Terradynamic Simulation Group University of MontanaMissoulaMTUSA Barcelona Expert Center Institut de Ciencies del MarICM-CSICBarcelonaSpain IBIMET-CNR Sesto FiorentinoItaly Fundacion CEAM PaternaSpain

The capacity of six water stress factors(ε′(i))to track daily light use efficiency(ε)of water-limited ecosystems was evaluated.These factors are computed with remote sensing operational products and a limited amount of ground data:ε′1 uses ground precipitation and air temperature,and satellite incoming global solar radiation;ε′(2) uses ground air temperature,and satellite actual evapotranspiration and incoming global solar radiation;ε′_(3) uses satellite actual and potential evapotranspiration;ε′_(4) uses satellite soil moisture;ε′_(5) uses satellite-derived photochemical reflectance index;and ε′_(6) uses ground vapor pressure deficit.These factors were implemented in a production efficiency model based on Monteith’s approach in order to assess their performance for modeling gross primary production(GPP).Estimated GPP was compared to reference GPP from eddy covariance(EC)measurements(GPP EC)in three sites placed in the Iberian Peninsula(two open shrublands and one savanna).ε′_(i) were correlated to ε,which was calculated by dividing GPP EC by ground measured photosynthetically active radiation(PAR)and satellite-derived fraction of absorbed PAR.Best results were achieved by ε′(1),ε′(2),ε′(3) and ε′(4) explaining around 40% and 50% of ε variance in open shurblands and savanna,respectively.In terms of GPP,R^(2)≈0.70 were obtained in these cases.

关键词： Light use efficiency water stress GPP Monteith Mediterranean ecosystems

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Endoscopic ultrasound and magnetic resonance imaging for re-staging rectal cancer after radiotherapy

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World Journal of Gastroenterology 2009年第44期15卷 5563-5567页

作者： Gianni Mezzi Paolo Giorgio Arcidiacono Silvia carrara Francesco Perri maria Chiara Petrone Francesco De Cobelli Simone Gusmini Carlo Staudacher Alessandro Del Maschio Pier Alberto Testoni Gastroenterology and Gastrointestinal Endoscopy Unit IRCCS Vita-Salute UniversitySan Raffaele Scientific Institute20132 MilanItaly Gastroenterology Unit San Benedetto del Tronto Hospital63039 San Benedetto del Tronto (AP)Italy Alessandro Del Maschio Department of RadiologyIRCCS Vita-Salute UniversitySan Raffaele Scientific Institute20132 MilanItaly Department of Surgery IRCCS Vita-Salute UniversitySan Raffaele Scientific Institute20132 MilanItaly

AIM:To compare the sensitivity and specificity of two imaging techniques,endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI),in patients with rectal cancer after neoadjuvant chemoradiation therapy. And we compared EUS and MRI data with histological fi ndings from surgical specimens. METHODS:Thirty-nine consecutive patients (51.3% Male; mean age:68.2 ± 8.9 years) with histologically confirmed distal rectal cancer were examined for staging. All patients underwent EUS and MRI imaging before and after neoadjuvant chemoradiation therapy. RESULTS:After neoadjuvant chemoradiation,EUS and MRI correctly classified 46% (18/39) and 44% (17/39) of patients,respectively,in line with their histological T stage (P > 0.05). These proportions were higher for both techniques when nodal involvement was considered:69% (27/39) and 62% (24/39). When patients were sorted into T and N subgroups,the diagnostic accuracy of EUS was better than MRI for patients withT0-T2 (44% vs 33%,P > 0.05) and N0 disease (87% vs 52%,P = 0.013). However,MRI was more accurate than EUS in T and N staging for patients with more advanced disease after radiotherapy,though these differences did not reach statistical significance. CONCLUSION:EUS and MRI are accurate imaging techniques for staging rectal cancer. However,after neoadjuvant RT-CT,the role of both methods in the assessment of residual rectal tumors remains uncertain.

关键词：磁共振成像直肠癌内镜超声放疗成像技术 MRI 平均年龄

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Tumors and new endoscopic ultrasound-guided therapies

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World Journal of Gastrointestinal Endoscopy 2013年第4期5卷 141-147页

作者： Silvia carrara maria Chiara Petrone Pier Alberto Testoni Paolo Giorgio Arcidiacono Scientific Institute San Raffaele Vita-Salute San Raffaele University

With the advent of linear echoendoscopes, endoscopic ultrasound (EUS) has become more operative and a new field of oncological application has been opened up. From tumor staging to tissue acquisition under EUS-guided fine-needle aspiration, new operative procedures have been developed on the principle of the EUS-guided puncture. A hybrid probe combining radiofrequency with cryotechnology is now available, to be passed through the operative channel of the echoendoscope into the tumor to create an area of ablation. EUS-guided fine-needle injection is emerging as a method to deliver anti-tumoral agents inside the tumor. Ethanol lavage, with or without paclitaxel, has been proposed for the treatment of cystic tumors in non-resectable cases and complete resolution has been recorded in up to 70%-80%. Many other chemical or biological agents have been investigated for the treatment of pancreatic adenocarcinoma: activated allogenic lymphocyte culture (Cytoimplant), a replication-deficient adenovirus vector carrying the tumor necrosis factor-α gene, or an oncolytic attenuated adenovirus (ONYX-015). The potential advantage of treatment under EUS control is the real-time imaging guidance into a deep target likethe pancreas which is extremely difficult to reach by a percutaneous approach. To date there are no randomized controlled trials to confirm the real clinical benefits of these treatments compared to standard therapy so it seems wise to reserve them only for experimental protocols approved by ethics committees.

关键词： Endoscopic ultrasound Pancreatic cancer Endoscopic ultrasound guided ablation Alcohol injection Anti-tumoral injection

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