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Liver decompensation predicts ribavirin overexposure in hepatitis C virus patients treated with direct-acting antivirals

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World Journal of Hepatology 2017年第34期9卷 1270-1277页

作者： Viola Guardigni Lorenzo Badia Matteo Conti Matteo Rinaldi Rita Mancini Pierluigi Viale gabriella Verucchi Department of Medical and Surgical Sciences University of Bologna S.Orsola-Malpighi Hospital Research Centre for the Study of Hepatitis University of Bologna Metropolitan Laboratory Maggiore Hospital

AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.

关键词： Hepatitis C Direct-acting antivirals Ribavirin Therapeutic drug monitoring Decompensated cirrhosis

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Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats

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World Journal of Gastroenterology 2005年第36期11卷 5677-5684页

作者： Luciano Onori Annalisa Aggio Simona D'Alo' Paola Muzi Maria Grazia Cifone gabriella Mellillo Rachele Ciccocioppo Gennaro Taddei Giuseppe Frieri Giovanni Latella Department of Internal Medicine and Public Health University of L' Aquila 67100 L'Aquila Italy Department of Experimental Medicine University of L' Aquila 67100 L'AquilaItaly Department of Preclinical Pharmacology Dompě SPA Research Center 67100 L'Aquila Italy

AIM： To evaluate the role of nitric oxide （NO） in the motor disorders of the dilated uninflamed mid-colon （DUMC） from trinitrobenzene sulfonic acid （TNBS）-induced acute distal colitis in rats. METHODS： Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS. Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration. Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase （MPO） and nitric oxide synthase （NOS） activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-L- arginine （L-NNA）. Pharmacological characterization of electric field stimulation （EFS）-evoked contractile responses was also performed. RESULTS： In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity. Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats. Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachyldnergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls. CONCLUSION： The results

关键词： TNBS colitis Colonic dilatation Colonic motility Nitric oxide synthase

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LEFM and Cohesive-Crack Approaches to Safety Evaluation of Concrete Gravity Dams

LEFM and Cohesive-Crack Approaches to Safety Evaluation of C...

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The Sixth World Congress on Computational Mechanics in Conjunction with the Second Asian-Pacific Congress on Computational Mechanics

作者： gabriella Bolzon Department of Structural Engineering Politecnico di Milano piazza Leonardo da Vinci 32 Milano 120133 Italy

Linear Elastic Fracture Mechanics (LEFM) is often used to analyze crack propagation and safety margin of large structures such as concrete gravity dams;see, e.g., [1 -2]. LEFM is an undoubtedly attractive approach when results have to be transferred from prototype to real dimensions, as in the case of centrifuge modeling [2]. In this case, in fact, the nominal strength of self-similar structures can be related to one dimensional parameter only, the material characteristics being captured by fracture energy;see, e.g., the comprehensive treatise [3] and references therein. On the other hand, cohesive-crack models, eventually resting on simplified hypothesis leading to direct methods as outlined in [4], can be used for safety assessment in this context and more naturally account for peculiar features such as friction in mixed mode fracture.

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A Case-Control Study on Leisure Time Physical Activity (LTPA) during the Last Three Months of Pregnancy and Foetal Outcomes in Italy

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Health 2016年第2期8卷 133-143页

作者： Guglielmina Fantuzzi Elena Righi gabriella Aggazzotti Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy

The association between Leisure Time Physical Activity (LTPA) during pregnancy and foetal outcomes has been extensively investigated. However, epidemiological studies specifically referred to LPTA in the last months of pregnancy are scarce. We evaluated the association between LPTA and the risk of both preterm delivery and small for gestational age (SGA) during the last three months of pregnancy in Italy. A nationwide case-control study was performed in nine Italian cities. A total of 299 preterm delivery, 364 SGA and 855 controls were enrolled in the study. A self-administered questionnaire was used to assess socio-demographic variables, medical and reproductive history, life-style habits and LTPA referred to the last three months of pregnancy. Univariate and multivariate regression analyses were performed in order to estimate Odds ratios and 95% CI. LTPA during the last three months of pregnancy decreases the risk of preterm delivery (adjusted OR = 0.56;95% CI 0.39 - 0.79). Among the different types of physical activity, walking, the most frequently referred activity, appears significantly protective against preterm delivery (adjusted OR = 0.53;95% CI 0.36 - 0.81). Moreover, a small protective effect of walking was evidenced against SGA (adjusted OR = 0.72;95% CI 0.51 - 1.00). In conclusion, a mild physical activity such as walking in the last three months of pregnancy seems to reduce the risk of preterm delivery and, at a lesser extent, of SGA, confirming the beneficial effects of physical activity along the whole pregnancy.

关键词： Leisure Time Physical Activity (LTPA) Preterm Delivery Small for Gestational Age Last Three Months of Pregnancy Case Control Study

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THE ASSOCIATION OF VACCINIA VIRUS WITH INTERMEDIATE FILAMENT

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Science China Chemistry 1988年第1期 28-38页

作者：翟中和,gabriella KROCHMALNIC,SHFLDON PENMAN Department of Biology Peking University Department of Biology Massachusetts Institute of Technology Cambridge USA Department of Biology Massachusetts Institute of Technology Cambridge USA

The intermediate filament-lamina-nuclear matrix system (IF-lamina-Nm System) can be shown clearlyusing selective extraction, embedment-free electron microscopy and whole mount cell preparation. A del-icate intermediate filament network was demonstrated in vaccinia virus factory for the first time. It isa part of the cytoplasmic intermediate filament network. The components and substructures of vacciniavirus bind firmly to intermediate filaments. Both assembled and assembling vaccinia viruses are fixedin the intermediate filament network. Direct connections between viruses and intermediate filaments canbe observed. We propose that vaccinia virus assembly depends on intermediate filaments as support.

关键词： THE ASSOCIATION OF VACCINIA VIRUS WITH INTERMEDIATE FILAMENT

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Big Data Research in Italy： A Perspective

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Engineering 2016年第2期2卷 163-170页

作者： Sonia Bergamaschi Emanuele Carlini Michelangelo Ceci Barbara Furletti Fosca Giannotti Donato Malerba Mario Mezzanzanica Anna Monreale gabriella Pasi Dino Pedreschi Raffele Perego Salvatore Ruggieri Department of Engneering "Enzo Ferrari " University of Modena and Reggio Emilia Modena 41125 Italy High Performance Computing Laboratory Institute of Information Science and Technologies of the Italian National Research Council (ISTI-CNR) Pisa 56124 Italy Department of Computer Science University ofBari Aldo Moro Bari 70125 Italy Knowledge Discovery and Data Mining Laboratory ISTI-CNR Pisa 56127 Italy Big Data Laboratory National Interuniversity Consortium for Informatics Rome 00185 Italy Department of Statistics and Quantitative Methods University of Milano-Bicocca Milan 20126 Italy Department of Computer Science Systems and Communications University of Milano-Bicocca Milan 20126 Italy Department of Computer 5denee University of Pisa Pisa 56127 Italy

The aim of this article is to synthetically describe the research projects that a selection of Italian univer- sities is undertaking in the context of big data. Far from being exhaustive, this article has the objective of offering a sample of distinct applications that address the issue of managing huge amounts of data in Italy, collected in relation to diverse domains.

关键词： Big data Smart cities EnergyJob offersPrivacy

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3D （Three-Dimensional） Caco-2 Spheroids： Optimized in vitro Protocols to Favor Their Differentiation Process and to Analyze Their Cell Growth Behavior

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Journal of Pharmacy and Pharmacology 2016年第7期4卷 341-350页

作者： gabriella Rainaldi Alessandra Boe Sandra Gessani Department of Hematology Oncology and Molecular Medicine lstituto Superiore di Sanit& Rome Italy

3D （Three-dimensional） Caco-2 spheroids closely recapitulating in vivo physiological organization of intestinal epithelial cells, provide an excellent in vitro model system to study their pathophysiology and their response to stressful stimuli. The objective of this technical note is to provide optimized in vitro experimental protocols for culturing 3D Caco-2 spheroids and for analyzing their cell growth features. An optimized 3D Caco-2 spheroid culturing technique based on a new configuration of the culture medium is provided A methodological approach to determine the distribution of the cell cycle phases in disaggregated Caco-2 spheroids by using cytofluorimetric analysis is also described. The optimized culturing protocol favors 3D Caco-2 spheroid differentiation process, as evaluated by the number of well-differentiated spheroids with a single hollow lumen. The cytofluorimetric analysis allows rapid collection of cell cycle phase data from high numbers of spheroid samples, thus, permitting to estimate their growth dynamics in a relatively short time. The optimized technical approaches described here can be applied in systematic manner to a variety of research activities utilizing 3D Caco-2 spheroids. Ease of use, time and economic saving advantages deriving from these protocols further highlight their potential.

关键词： 3D multicellular spheroids 3D intestinal epithelial spheroids 3D Caco-2 spheroid culture systems optimizedexperimental protocols.

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Molecular Typing of Clinical and Environmental <i>Cryptococcus neoformans</i>Strains Isolated in Italy

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Open Journal of Medical Microbiology 2017年第4期7卷 77-85页

作者： gabriella Pini Elisabetta Faggi Eleonora Bravetti Department of Experimental and Clinical Medicine University of Florence Florence Italy

Cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. DNA molecular typing techniques divided C. neoformans into four major molecular types (AFLP1/VNI, AFLP1A/VNB/VNII, AFLP1B/ VNII, AFLP3/VNIII, AFLP2/VNIV) characterized by different pathogenicity, geographical distribution and susceptibility to antifungal treatments. In this study 170 Italian C. neoformans clinical isolates (CI) and 32 environmental isolates (EI), collected and serotyped during a ten-year period (1985 to 1995), were genotyped using [GACA]4 microsatellite PCR fingerprinting. The molecular types were compared to their geographic distribution, specimen sources and patient’s risk factors. All four molecular types were described among the CI and only VNI and VNIV among the EI. VNIV molecular type was isolated with significant prevalence among the CI and VNI among the EI. A different geographical distribution of molecular types was detected: VNIV was the most prevalent in the North and Center of Italy;VNIII was isolated almost exclusively in the Center. No significant correlation among molecular types versus predisposing diseases or isolation sources was detected. The strains isolated from different body sites of the same patient (17 cases) were of the same genotype. Five out 9 cases relapsed with a different molecular type. This preliminary investigation shows a high intraspecies variability and reveals a nonhomogeneous distribution of C. neoformans molecular types in Italy.

关键词： Cryptococcus neoformans Clinical Isolates Environmental Isolates Molecular Typing Molecular Types Distribution

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On the Dynamic Equilibrium in Homeostasis

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Open Journal of Biophysics 2012年第3期2卷 60-67页

作者： gabriella Hegyi Gyula Vincze Andras Szasz Department of Biotechnics St. Istvan University Godollo Hungary Department of Complementary Medicine University of Pécs Pécs Hungary

We studied the homeostatic equilibrium of the healthy organism. The homeostasis is controlled by oppositely effective physiologic feedback signal-pairs in various time-scales. We show the entropy of every signal in this state is identical and constant: SE = 1.8. The controlling physiological signals fluctuate around their average values. The fluctuation is time-fractal, (pink-noise), which characterizes the homeostasis. The aging is the degradation of the competing pairs of signals, decreasing the complexity of the organism. This way, the color of the noise gradually changes to brown. A special scaling process occurs during the aging: the exponent of the frequency dependence of the power density function grows in this process from 1 to 2, but the homeostasis of the system is unchanged.

关键词： Homeostasis Entropy Bioscaling Aging Competing Feedback-Signals Multiscaling Entropy MSE

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Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

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World Journal of Gastroenterology 2016年第11期22卷 3202-3211页

作者： Alfredo Di Leo gabriella Nesi Mariabeatrice Principi Domenico Piscitelli Bruna Girardi Maria Pricci Giuseppe Losurdo Andrea Iannone Enzo Ierardi Francesco Tonelli Gastroenterology Section Department of Emergency and Organ TransplantationUniversity of Bari Pathology Section Department of Surgery and Translational MedicineUniversity of Florence Pathology Section Department of Emergency and Organ TransplantationUniversity of Bari General Surgery Section Department of Surgery and Translational MedicineUniversity of Florence

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis ***: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni’s test, and Pearson’s correlation test were applied for statistical ***: ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson’s correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic ***: This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple

关键词： Familial adenomatous polyposis Duodenal cancer Estrogen receptors Immunohistochemistry Confocal microscopy Dysplasia

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