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Thrombin activation and liver inflammation in advanced hepatitis C virus infection

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World Journal of Gastroenterology 2016年第18期22卷 4427-4437页

作者： Emilio gonzález-Reimers Geraldine Quintero-Platt candelaria martín-gonzález Onán Pérez-Hernández Lucía Romero-Acevedo Francisco Santolaria-Fernández Servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna

Hepatitis C virus(HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

关键词： Coagulation Liver cirrhosis Hepatitis C virus Fibrogenesis Parenchymal extinction Portal thrombosis Protein C

Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

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World Journal of Hepatology 2016年第1期8卷 74-82页

作者： emilio gonzález-reimers javier lópez-prieto geraldine quintero-platt ricardo pelazas-gonzález m remedios alemán-valls onán pérez-hernández m joséde-la-vega-prieto m angeles gómez-rodríguez candelaria martín-gonzález francisco santolaria-fernández Servicio de Medicina Interna Hospital Universitario de CanariasUniversidad de La Laguna38320 Canary IslandsSpain

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) ***: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. no differences were observed in leptin and ***: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

关键词： Resistin Adiponectin Insulin resistance Proinflammatory cytokines Leptin Hepatitis C virus Liver steatosis

Patients with hepatocellular carcinoma that die during the first year of liver transplantation have high blood sFasL concentrations

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World Journal of Clinical Cases 2023年第8期11卷 1753-1760页

作者： Leonardo Lorente Sergio T Rodriguez Pablo Sanz Agustín F gonzález-Rivero Antonia Pérez-Cejas Javier Padilla Dácil Díaz Antonio gonzález maría M martín Alejandro Jiménez Purificación Cerro Julián Portero Manuel A Barrera Intensive Care Unit Hospital Universitario de CanariasLa Laguna 38320Spain Intensive Care Unit Hospital Universitario Nuestra Señora CandelariaSanta Cruz Tenerife 38010Spain Department of Surgery Hospital Universitario Nuestra Señora de CandelariaSanta Cruz Tenerife 38010Spain Department of Laboratory Hospital Universitario de CanariasLa Laguna 38320Spain Department of Digestive Hospital Universitario Nuestra Señora de CandelariaSanta Cruz Tenerife 38010Spain Research Unit Hospital Universitario de CanariasLa Laguna 38320Spain Transplant Unit Hospital Universitario Nuestra Señora CandelariaSanta Cruz Tenerife 38010Spain Department of Radiology Hospital Universitario Nuestra Señora CandelariaSanta Cruz Tenerife 38010Spain

BACKGROUnD Fas ligand(FasL)is one ligand that activates extrinsic apoptosis *** expression in lymphocytes of FasL have been found in patients with acute rejection of liver transplantation(LT).no high blood concentrations of soluble FasL(sFasL)have been found in patients with acute LT rejection;however,the samples size of those studies was *** To determine whether patients with hepatocellular carcinoma(HCC)that dead during the first year of LT have higher blood sFasL concentrations previously to LT that those who that remain alive in a study of higher sample *** Patients underwent LT due to HCC were included in this retrospective *** sFasL levels prior to LT were measured and one-year LT mortality was *** non-surviving patients(n=14)showed higher serum sFasL levels[477(269-496)vs 85(44-382)pg/mL;Pn surviving patients(n=113).Serum sFasL levels(pg/mL)were associated with mortality(OR=1.006;95%CI=1.003-1.010;P=0.001)independently of age of LT donor in the logistic regression *** We report for the first time that HCC patients who die within the first year of HT have higher blood sFasL concentrations prior to HT than those who remain alive.

关键词： sFasL Hepatocellular carcinoma Liver transplantation Mortality Outcome

DnA and RnA oxidative damage in hepatocellular carcinoma patients and mortality during the first year of liver transplantation

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World Journal of Hepatology 2022年第6期14卷 1182-1189页

作者： Leonardo Lorente Sergio T Rodriguez Pablo Sanz Agustín F gonzález-Rivero Antonia Pérez-Cejas Javier Padilla Dácil Díaz Antonio gonzález maría M martín Alejandro Jiménez Purificación Cerro Julián Portero Manuel A Barrera Department ofIntensive Care Hospital Universitario de CanariasLa Laguna 38320TenerifeSpain Intensive Care Unit Hospital Universitario Nuestra Señora CandelariaSanta Cruz de Tenerife 38010Spain Department of Surgery Hospital Universitario Nuestra Señora de CandelariaSanta Cruz de Tenerife 38010Spain Department of Laboratory Hospital Universitario de CanariasLa Laguna 38320Spain Department of Digestive Hospital Universitario Nuestra Señora de CandelariaSanta Cruz de Tenerife 38010Spain Research Unit Hospital Universitario de CanariasLa Laguna 38320Spain Transplant Unit Hospital Universitario Nuestra Señora CandelariaSanta Cruz de Tenerife 38010Spain Department of Radiology Hospital Universitario Nuestra Señora CandelariaSanta Cruz de Tenerife 38010Spain

BACKGROUnD Oxidative damage of DnA and RnA has been associated with mortality of patients with different ***,there is no published data on the potential use of DnA and RnA oxidative damage to predict the prognosis of patients with hepatocellular carcinoma(HCC)undergoing liver transplantation(LT).AIM To determine whether patients with increased DnA and RnA oxidative damage prior to LT for HCC have a poor LT *** Patients with HCC who underwent LT were included in this observational and retrospective *** levels of all three oxidized guanine species(OGS)were measured prior to LT since guanine is the nucleobase that forms DnA and RnA most prone to *** mortality at 1 year was the end-point *** Surviving patients(n=101)showed lower serum OGS levels(P=0.01)and lower age of the liver donor(P=0.03)than non-surviving patients(n=13).An association between serum OGS levels prior to LT and 1-year LT(odds ratio=2.079;95%confidence interval=1.356-3.189;P=0.001)was found in the logistic regression *** The main new finding was that high serum OGS concentration prior to LT was associated with the mortality 1 year after LT in HCC patients.

关键词： DnA oxidative damage Hepatocellular carcinoma Liver transplantation Mortality Oxidized guanine species

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage

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World Journal of Critical Care Medicine 2023年第2期12卷 63-70页

作者： Leonardo Lorente maría M martín Antonia Pérez-Cejas Luis Ramos-Gómez Jordi Solé-Violan Juan J Cáceres Alejandro Jiménez Agustín F gonzález-Rivero Department of Intensive Care Hospital Universitario de CanariasLa Laguna 38320TenerifeSpain Department of Intensive Care Hospital Universitario Nuestra Señora de CandelariaSanta Cruz de Tenerife 38010TenerifeSpain Department of Laboratory Hospital Universitario de CanariasLa Laguna 38320TenerifeSpain Department of Intensive Care Hospital Universitario de La PalmaBreña Alta 38713Spain Department of Critical Care Hospital Universitario de Gran Canaria Dr NegrinLas Palmas de Gran Canaria 35010Spain Department of Critical Care Universidad Fernando Pessoa CanariasLas Palmas de Gran Canaria 35450Spain Department of Intensive Care Hospital InsularLas Palmas de Gran Canaria 35016Spain Research Unit Hospital Universitario de CanariasLa Laguna 38320TenerifeSpain

BACKGROUnD Several studies of spontaneous intracerebral hemorrhage(SICH)patients have shown apoptotic changes in brain samples after hematoma ***,there have been no data on the association between blood concentrations of soluble fas(sFas)(the main surface death receptor of the extrinsic apoptosis pathway)and the prognosis of spontaneous intracranial hypotension(SIH)*** To determine whether there is an association between blood sFas concentrations and SICH patient *** We included patients with severe and supratentorial *** was defined as having Glasgow Coma Scalened serum sFas concentrations at the time of severe SICH *** We found that non-surviving patients(n=36)compared to surviving patients(n=39)had higher ICH score(P=0.001),higher midline shift(P=0.004),higher serum sFas concentrations(Pnd lower rate of early hematoma evacuation(P=0.04).Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality(odds ratio=1.070;95%confidence interval=1.014-1.129;P=0.01)controlling for ICH score,midline shift,and early hematoma *** The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.

关键词： Spontaneous intracerebral hemorrhage Soluble fas Apoptosis Patients Mortality

Variables of Suicidal Behavior in Tenerife Years 2011-2012: Proposals for the Prevention

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Forensic Medicine and Anatomy Research 2014年第2期2卷 37-41页

作者： Sergio Manuel martínez Aguilar Milagros De la Rosa Hormiga Juan Manuel Herrera Hernández Francisco Rodríguez Pulido candelaria de la Merced Díaz-gonzález Forensic Department Tenerife Spain Servicio Canario de la Salud Tenerife Spain Universidad de La Laguna Tenerife Spain

Suicide is treated by society as a taboo subject despite it being the leading cause of unnatural death in Spain. The Tenerife Province is ranked 16th among the 52 Spanish provinces for its suicide rate. From 2007 till 2010, the rate increased from 2007 to 2008, then dropped in 2010. Slight rise occurred in suicide rates in 2010. This rate increased from 2007 to 2008, with a decrease of rate in 2010. Slight rise occurred in suicide rates in 2010. In 2013 the province saw 75 suicides per year. 90% - 98% of suicides are closely related to mental disease with the remaining 10% associated with different poor causes of the subject, according to bibliography. In this retrospective study, it has been found that the highest risk rests with men over 40 years of age in the central and southern part of the island. Among the forms of suicide reported, the most common is hanging followed by jumping from a height. It’s important to understand the reasons behind suicidal behavior from a psychosocial perspective, taking into account “unsafe” indicators and individual profiles. The lethal nature of a suicide attempt also depends on the form of suicide adopted and the possibility of a rescue. Specific protocols to prevent suicide should be promoted and discussed between health and social services.

关键词： Consummated Suicide Autopsy Violent Death Autopsy Psychosocial

Implications of Klotho in vascular health and disease

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World Journal of Cardiology 2014年第12期6卷 1262-1269页

作者： Ernesto martín-núez Javier Donate-Correa Mercedes Muros-de-Fuentes Carmen Mora-Fernández Juan F navarro-gonzález Research Unit University Hospital Nuestra Se?ora de Candelaria 38010 Santa Cruz de Tenerife Spain Clinical Analysis Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain nephrology Service and Research Unit University Hospital Nuestra Se ora de Candelaria 38010 Santa Cruz de Tenerife Spain

Cardiovascular disease(CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of nO production and mediates antiinflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore,this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity.

关键词： Klotho Cardiovascular disease Vascular health Aging Endothelial dysfunction Vascular calcification

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

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World Journal of Gastroenterology 2017年第4期23卷 703-711页

作者： marisol Luján-Sanchis Enrique Pérez-Cuadrado-Robles Javier Garcia-Lledo José-Francisco Juanmartinena Fernandez Luca Elli Victoria-Alejandra Jiménez-García Juan Egea-Valenzuela Julio Valle-Munoz Cristina Carretero-Ribón Ignacio Fernández-Urién-Sainz Antonio López-Higueras noelia Alonso-Lazaro Mileidis Sanjuan-Acosta Francisco Sanchez-Ceballos Bruno Rosa Santiago gonzález-Vázquez Federica Branchi Lucía Ruano-Díaz César Prieto-de-Frías Vicente Pons-Beltrán Pilar Borque-Barrera Begona gonzález-Suárez Sofía Xavier Federico Argüelles-Arias Juan-Manuel Herrerías-Gutiérrez Enrique Pérez-Cuadrado-martínez Javier Sempere-García-Argüelles Digestive Diseases Unit General University Hospital of Valencia Small Bowel Unit Hospital Morales Meseguer Digestive Diseases Unit General University Gregorio Maranón Unit of Gastroenterology and Endoscopy Complejo Hospitalario de Navarra Center for prevention and Diagnosis of Celiac Disease Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Unit of Gastroenterology and Endoscopy University Hospital Virgen Macarena Gastroenterology department Hospital Virgen de la Arrixaca Department of Gastroenterology Complejo Hospitalario de Toledo Department of Gastroenterology University of Navarra Clinic1 Endoscopy Digestive Unit Digestive Diseases AreaUniversitari i Politècnic La Fe Hospital1 Digestive Diseases Unit University Hospital Nuestra Senora de Candelaria1 Digestive Diseases Unit Clinical Hospital San Carlos1 Digestive Diseases Unit Hospital da Senhora da Oliveira-Guimaraes1 Endoscopy Digestive Unit Hospital Clinic de Barcelona

AIMTo analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE).METHODSThis is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were *** overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P nd 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated *** has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.

关键词： Capsule endoscopy Celiac disease Anti-transglutaminase antibodies Gluten-free diet non-celiac gluten sensitivity

Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy

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World Journal of Diabetes 2012年第1期3卷 7-18页

作者： Desirée Luis-Rodríguez Alberto martínez-Castelao José Luis Górriz Fernando de lvaro Juan F navarro-gonzález Grupo Espaol para el Estudio de la nefropatía Diabética (GEEnDIAB) Spain nephrology Service and Research Unit University Hospital Nuestra Seora de Candelaria 38010 Santa Cruz de Tenerife Spain nephrology Service Bellvitge University Hospital 08907 L’Hospitalet de Llobregat Spain nephrology Service University Hospital Dr. Peset 46017 Valencia Spain nephrology Service University Hospital Infanta Sofía 28702 Madrid Sapin

Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe development and progression of renal injury are not well known. Therefore, it is very important to f ind new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.

关键词： Diabetes Diabetic nephropathy Innate immunity Inflammation Renal failure