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Hepatoprotective effects of antioxidants in chronic hepatitis C

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World Journal of Gastroenterology 2010年第15期16卷 1937-1938页

作者： ricardo moreno-otero María Trapero-Marugán Digestive Diseases Service and CIBEREHD (Instituto de Salud Carlos Ⅲ) University Hospital La Princesa Autonomous University of Ma-drid

We have read with interest the paper published in issue 2, volume 16 of World Journal of Gastroenterology 2010 by Nakamura et al, demonstrating that the antioxidant resveratrol (RVT) enhances hepatitis C virus (HCV) replication, consequently, they conclude that RVT is not a suitable antioxidant therapy for HCV chronic infection. The data raise some concern regarding the use of complementary and alternative medicine since the most frequent supplements taken by these patients are antioxidants or agents that may be beneficial for different chronic liver diseases. A recent study by Vidali et al on oxidative stress and steatosis in the progression of chronic hepatitis C concludes that oxidative stress and insulin resistance contribute to steatosis, thus accelerating the progression of fibrosis. We are particularly interested in investigating how the oxidative and nitrosative stress mechanisms are involved in the pathogenesis of different chronic liver diseases.

关键词： Antioxidant Chronic hepatitis C Resveratrol Sadenosylmethionine Nitric oxide Nacetylcysteine

Liver disease and erythropoietic protoporphyria:A concise review

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World Journal of Gastroenterology 2010年第36期16卷 4526-4531页

作者： María José Casanova-González María Trapero-Marugán E Anthony Jones ricardo moreno-otero Department of the Gastroenterology and Hepatology Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD)Madrid 28006Spain

The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of *** erythropoietic protoporphyria(EPP),in the majority of cases an autosomal dominant disease,there is a mutation of the gene that encodes ferrochelatase(FECH).FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes,plasma,skin and *** prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 *** manifestations of EPP appear in early infancy upon first exposure to the ***,approximately 5%-20% of patients with EPP develop liver *** of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity,such as cholelithiasis,mild parenchymal liver disease,progressive hepatocellular disease with end-stage liver disease and acute liver *** damage is the major risk in EPP patients,so surveillance and frequent clinical and biochemical liver follow-up is *** diagnostic approach consists in detecting increased levels of protoporphyrin,decreased activity of FECH and genetic analysis of the FECH gene.A variety of nonsurgical therapeutic approaches have been adopted for the management of EPP associated with liver disease,but none of these has been shown to be unequivocally ***,some may have a place in preparing patients for liver *** transplantation does not correct the constitutional deficiency of ***,there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of *** authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

关键词： Erythropoietic protoporphyria Protoporphyrin Liver Ferrochelatase

Interplay among cellular polarization,lipoprotein metabolism and hepatitis C virus entry

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World Journal of Gastroenterology 2011年第22期17卷 2683-2690页

作者： Ignacio Benedicto Francisca Molina-Jiménez ricardo moreno-otero Manuel López-Cabrera Pedro L Majano Molecular Biology Unit Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) Madrid 28006 Spain CIBERehd Instituto de Salud Car- los Ⅲ Madrid 28029 Spain Liver Unit Hospital Universitario de la Princesa Instituto de Investigación Sanitaria Princesa (IP) Madrid 28006 Spain Centro de Biología Molecular Severo Ochoa CSIC-UAM Madrid 28049 Spain

Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Given the lack of effective prophylactic or therapeutic vaccines, and the limited sustained virological response rates to current therapies, new approaches are needed to prevent, control, and clear HCV *** into the host cell, being the first step of the viral cycle, is a potential target for the design of new antiviral compounds. Despite the recent discovery of the tight junction-associated proteins claudin-1 and occludin as HCV co-receptors, which is an important step towards the understanding of HCV entry, the precise mechanisms are still largely unknown. In addition, increasing evidence indicates that tools that are broadly employed to study HCV infection do not accurately reflect the real process in terms of viral particle composition and host cell phenotype. Thus, systems that more closely mimic natural infection are urgently required to elucidate the mechanisms of HCV entry, which will in turn help to design antiviral strategies against this part of the infection process.

关键词：丙型肝炎病毒宿主细胞相互作用蛋白代谢入境极化急性感染病毒感染

Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

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世界胃肠病学杂志：英文版 2011年第4期17卷 493-498页

作者： María Trapero-Marugán Jorge Mendoza María Chaparro Leticia González-moreno José Andrés moreno-Monteagudo María Jesús Borque ricardo moreno-otero Gastroenterology-Hepatology Department University Hospital La Princesa and Princesa Research Institute Autonomous University of Madrid and CIBERehd (Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas)

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

关键词：丙型肝炎病毒利巴韦林聚乙二醇病毒学干扰素患者慢性反应

Desperately seeking hepatitis C virus

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World Journal of Gastroenterology 2008年第18期14卷 2946-2947页

作者： ricardo moreno-otero Hepato-Gastroenterology Service and Ciberehd Hospital Universitario de La Princesa Autonomous University of Madrid Madrid 28006 Spain

Spanish investigators described recently the so-called occult hepatitis C virus (HCV) infection, emphasizing the detection of genomic and antigenomic HCV RNA strands in liver and peripheral blood mononuclear cells. Therefore, the persistence of viral replication in occult HCV infection should be considered as a putative source of infection among family members and patients undergoing invasive procedures, transfusion or transplantation. Additionally, the most worrisome finding is that an occult HCV infection may persist in patients with sustained virological response.

关键词：丙型病毒肝炎病毒感染病毒复制治疗方法

Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

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World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-Rodríguez María Jesús Borque Leticia González-moreno Yolanda Real-Martínez Luisa García-Buey ricardo moreno-otero Paloma Sanz-Cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR *** were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in *** Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area under the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

Is interferon-beta an alternative treatment for chronic hepatitis C?

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World Journal of Gastroenterology 2006年第17期12卷 2730-2736页

作者： ricardo moreno-otero María Trapero-Marugán Elena Gómez-Domínguez Luisa García-Buey JoséA moreno-Monteagudo Unit of Hepatology Hospital Universitario de La Princesa Universidad Autónoma de MadridSpain

长期的丙肝(CHC ) 的治疗仍然是远非最佳的，特别地为不对有加 ribavirin 的 Interferon-alpha (IFNalpha ) 的标准联合治疗作出回应的那些潜水艇人口。尽管在一些情况中更高的剂量或更长的治疗经期的使用可能是有效的，这些途径通常与... 详细信息

长期的丙肝(CHC ) 的治疗仍然是远非最佳的，特别地为不对有加 ribavirin 的 Interferon-alpha (IFNalpha ) 的标准联合治疗作出回应的那些潜水艇人口。尽管在一些情况中更高的剂量或更长的治疗经期的使用可能是有效的，这些途径通常与不利事件的更高的发生被联系，它也可以在耐心的依从导致减小或要求药退却。IFNbeta 能为对待 CHC 病人代表一种有趣的选择。关于在 CHC 的 IFNbeta 功效的争论数据存在，是许多结果与病人的小队源自预研项目的主要原因。然而，有希望的结果在没能对 IFNalpha 作出回应的病人的一些亚群被获得了。另外， IFNbeta 的好 toler 能力代表这药的一个重要优点。在控制临床的试用的退学学生的率，以及对剂量减小或治疗中止的需要是很低的。它可能值得与病人，不是合格容忍的标准治疗的一个更大的队在使随机化的研究估计 IFNbeta 正 ribavirin 的价值，并且为非应答者。

关键词：干扰素-β 丙型病毒肝炎唑核苷病毒唑病毒感染

Comprehensive Euler/Lagrange modelling including particle erosion for confined gas-solid flows

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Particuology 2024年第1期84卷 209-235页

作者： Guiherme A.Novelletto ricardo Martin Sommerfeld Multiphase Flow Systems Institute of Process EngineeringOtto-von-Guericke-University MagdeburgHoher Weg 7b06120Halle(Saale)Germany

The present research aims to assess the capability of a comprehensive Euler/Lagrange approach for predicting gas-solid flows and the associated solid particle *** open-source code OpenFOAM®4.1 was used to carry out the numerical simulations,where the standard Lagrangian libraries were substantially extended to account for all necessary *** are tracked considering both translational and rotational motion as well as all relevant forces,such as gravity/buoyancy,drag and transverse lift due to shear and particle *** tracking time step was dynamically adapted ac-cording to the locally relevant time scales,which drastically reduces computational *** approaches are adopted to model particle turbulent dispersion,particle collisions with rough walls and particle-particle *** solid particle erosion models,available in the literature,were considered to estimate pipe bend *** study cases are provided to validate the adopted nu-merical approach and erosion models *** first case intends to evaluate the ability of the extended CFD code to predict the behaviour of gas-solid flows in pneumatic conveying *** goal is achieved by comparing the numerical results with the experimental data obtained by Huber(1997)and Huber and Sommerfeld(1994,1998)in a pneumatic conveying ***,the importance of considering inter-particle collisions and surface roughness for predicting particle velocity,mass flux and mean diameter distributions in gas-solid flows is *** second and third case intend to evaluate the ability of the erosion models in estimating bend erosion in diluted gas-solid *** erosion data obtained experimentally by Mazumder et al.(2008)and Solnordal et al.(2015)in very dilut pneumatic conveying systems is used for validating the numerical results,neglecting now inter-particle collisions and two-way *** a comprehensive analysis of the different influential properti

关键词： Pneumatic conveying Pipe bend Numerical calculation(CFD) Euler/Lagrange approach Erosion models Wall roughness

Testicular prostheses-impact on quality of life and sexual function

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Asian Journal of Andrology 2024年第2期26卷 160-164页

作者： Ana Sofia Araujo Sara Anacleto ricardo Rodrigues Catarina Tinoco Andreia Cardoso Carlos Oliveira ricardo Leao Department of Urology Braga's HospitalBraga 4710Portugal Faculty of Medicine Coimbra UniversityCoimbra 3000Portugal

Orchiectomy is the recommended treatment for many testicular ***,testicular prosthesis placement is not always performed for different *** this study,we aimed to evaluate patients'opinions and the impact on sexual function and quality of *** retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology,Braga's Hospital(Braga,Portugal),where testicular implants were always available and the decision to undergo the procedure was made fully independent of *** completed four questionnaires that assessed demographic data,satisfaction,self-esteem,and sexual *** the 96 patients who underwent orchidectomy,59 replied to the questionnaires,and of these patients,86.4%decided to undergo silicone-based testicular prostheses *** remaining 13.6%refused the implant based on concerns about complications(37.5%),because they felt that it was unnecessary(37.5%),or because it was not offered by the doctor(25.0%).Overall,96.1%of these patients were satisfied with the implant;however,25.5%classified it as"too firm".No statistically significant differences were found in sexual function(all P>0.05).However,it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses(74.0%vs 50.0%),and none of them reported severe erectile dysfunction(0 vs 16.7%).Regarding self-esteem,both patients with and without prostheses present very similar average scores with no statistically significant *** present study highlights the highest level of satisfaction among patients who received testicular *** prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.

关键词： orchiectomy patient satisfaction quality of life sexual dysfunction sexual health testicular prostheses