The Campo de Dalias GNSS Network Unveils the Interaction between Roll-Back and Indentation Tectonics in the Gibraltar Arc.

The Gibraltar Arc includes the Betic and Rif Cordilleras surrounding the Alboran Sea; it is formed at the northwest-southeast Eurasia-Nubia convergent plate boundary in the westernmost Mediterranean. Since 2006, the Campo de Dalias GNSS network has monitored active tectonic deformation of the most seismically active area on the north coast of the Alboran Sea. Our results show that the residual deformation rates with respect to Eurasia range from 1.7 to 3.0 mm/year; roughly homogenous west-southwestward displacements of the northern sites occur, while the southern sites evidence irregular displacements towards the west and northwest. This deformation pattern supports simultaneous east-northeast-west-southwest extension, accommodated by normal and oblique faults, and north-northwest-south-southeast shortening that develops east-northeast-west-southwest folds. Moreover, the GNSS results point to dextral creep of the main northwest-southeast Balanegra Fault. These GNNS results thus reveal, for the first time, present-day interaction of the roll-back tectonics of the Rif-Gibraltar-Betic slab in the western part of the Gibraltar Arc with the indentation tectonics affecting the eastern and southern areas, providing new insights for improving tectonic models of arcuate orogens.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

INTRODUCTION: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. METHODS: NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. RESULTS: Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). CONCLUSION: The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Intrahepatic angiopoietin-2 correlates with chronic hepatitis C progression and is induced in hepatitis C virus replicon systems.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) is a major cause of cirrhosis and hepatocellular carcinoma and angiogenesis is closely related to the pathogenesis and progression of different chronic liver diseases (CLD). Thus, the intrahepatic expression of angiopoietins 1 and 2 (Ang1 and Ang2), as relevant mediators of pathological angiogenesis in several CLD, was investigated. In addition, the differential influence of structural and non-structural genomic regions of HCV on the expression of angiopoietins and the possible signalling involved were studied. METHODS: Ang1 and Ang2 expression was evaluated by western blotting and enzyme-linked immunosorbent assay (ELISA) in liver homogenates of CHC patients (n=47) and uninfected subjects (n=8). Their association with disease progression (according to METAVIR classification) was assessed by Spearman's correlation. Statistical differences among the expression of angiopoietins at different CHC stages were calculated by Mann-Whitney U-test. Finally, the in vitro expression of Angiopoietins in HCV replicons (complete or non-structural subgenomic) and the main signalling pathways involved were also examined. RESULTS: Ang2 levels were significantly higher in the liver of CHC patients compared to controls and significantly correlated with inflammation and fibrosis. Accordingly, an increased expression of Ang2 was found in all HCV replicons tested. Interestingly, the inhibition of MEK and PI3K signalling pathways exerted differential effects on Ang2 expression concerning to the genomic region of HCV. CONCLUSIONS: Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.

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

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 system. Groups were compared by non-parametric Mann-Whitney 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 CHC. CONCLUSION: 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.

Análisis del estado nutricional y composición corporal de personas con discapacidad intelectual / Analysis of the nutritional status and body composition of persons with intellectual disability

Introducción. La discapacidad intelectual, definida como limitaciones sustanciales en el funcionamiento intelectual, afecta al 0,7-1,5% de la población. Estas personas presentan mayores tasas de obesidad, y sus valores calóricos y estado nutricional son deficientes. Objetivos. Conocer los hábitos nutricionales, analizar la eficacia de la educación nutricional y evaluar la posible mejora, introduciendo talleres de ejercicio físico y nutrición, en la discapacidad intelectual. Pacientes y métodos. Se realizó una valoración clínica, nutricional y antropométrica (peso, talla, índice de masa corporal, grasa corporal, perímetro de la cintura) a 47 sujetos con discapacidad intelectual. Se registraron los hábitos deportivos, la historia clínica y la historia dietética mediante un registro alimentario y un cuestionario de adhesión a la dieta mediterránea (KidMed). Los talleres de nutrición y ejercicio físico contaron con una estructura de explicación teórica, práctica y juegos. Resultados. El 76,1% presentaba exceso ponderal en el inicio del estudio. Tras la intervención, los valores de grasa corporal (-0,94 ± 4,4%) y grasa visceral (-0,86 ± 2%), así como el peso (-0,4 ± 3,3 kg) y el índice de masa corporal (-0,2 ± 1,6 kg/m2), disminuyeron, más en las mujeres que en los hombres. El 60,5% no cumplía con una alta adhesión a la dieta mediterránea. Tras la intervención, se observó una diferencia significativa (p ≤ 0,001) en la puntuación del KidMed. El taller de actividad física tuvo efectos positivos sobre la antropometría. Conclusiones. La alimentación fue inadecuada en la mayoría de los individuos. La prevalencia de obesidad fue elevada. Los talleres de educación nutricional y de ejercicio son una herramienta útil para trabajar con este colectivo, y consiguen cambios significativos para prevenir la obesidad y mejorar su salud (AU)

Introduction. Intellectual disability refers to substantial limitations in intellectual functioning, affecting 0.7-1.5% of the population. People with intellectual disability have higher rates of obesity, since caloric values and nutritional status, are deficient. Aims. To determine the nutritional habits, analyze the effectiveness of nutritional education and evaluate the possible effect of improvement introducing exercise and nutrition workshops, in a group of people with intellectual disability. Patients and methods. Clinical, nutritional and anthropometric (weight, height, body mass index, body fat, waist circumference) assessment was conducted in 47 patients. An ad hoc survey was designed in which exercise habits, medical and dietary history, record of 72 hours (including 2 weekdays and 1 weekend) and the adherence to Mediterranean diet data were collected. The workshops of exercise and nutrition counted with a structure of theoretical-practical explanation and games. Results. 76.1% presented weight excess at baseline. After the intervention values of total body fat (-0.94 ± 4.4%) and visceral fat (-0.86 ± 2%), weight (-0.4 ± 3.3 kg) and body mass index (-0.2 ± 1.6 kg/m2) decreased, more in women than in men. 60.5% of subjects did not meet a high adherence to the Mediterranean diet. After nutritional intervention, a significant difference (p ≤ 0,001) was observed in the KidMed score. The workshop of physical activity had positive effects on the anthropometry of subjects. Conclusions. Both the intake and the prevalence of obesity in this group of people are inadequate. Nutritional education and physical exercise workshops are useful for working with this group, achieving significant changes to prevent obesity and improve their health (AU)

Hábitos alimentarios y psicológicos en personas que realizan ejercicio físico / Nutritional and psychological habits in people who practice exercise

Introducción: La distorsión de la imagen corporal se ha convertido en un problema mundial. La delgadez como patrón de belleza para las mujeres, y la musculación para los hombres, se han relacionado con el incremento de los Trastornos de la Conducta Alimentaria (TCA). La práctica de ejercicio físico con fines estéticos o adictivos ha incrementado, así como la popularización de los gimnasios. Objetivos: Analizar los comportamientos ortoréxicos, conocer la influencia del género en los comportamientos psicológicos y analizar los hábitos de alimentación de una muestra que practica actividad física. Métodos: Estudio observacional, descriptivo y retrospectivo en el que se realizó un cuestionario ad hoc, incorporando el test de Adherencia a Dieta Mediterránea, el Inventario de Expresión de Ira Estado-Rasgo (STAXI-2), el Cuestionario de Comedor Emocional (EEQ) adaptado y la versión española del Multidimensional Body Self Relations Questionnaire (MBSRQ). Además se realizó una valoración antropométrica a cada participante. Resultados: 264 sujetos fueron incluidos en el estudio (156 hombres), de 35,9 años (±11,1 años). Con IMC medio de 23,8 kg/m2 (±3,1 kg/m2 ) y un porcentaje de grasa corporal total 20,8 (±8,7%). La puntuación media la Adherencia a la Dieta Mediterránea, fue 5,9 (±2,4). Se encontraron comportamientos de carácter ortorexico y obsesivo, y diferencias entre géneros, para algunos marcadores estudiados. Conclusiones: Los hábitos analizados ponen de manifiesto una tendencia al culto al cuerpo, más próximo al extremo patológico que al aspecto saludable, provocando alteraciones sobre la percepción, que traen como consecuencia la realización de dietas y la aparición de alteraciones como los TCA (AU)

Introduction: The distorted body image has become a global problem. The thinness as a standard of beauty for women, and fitness for men, has been linked to an increase in eating behavior disorders. The physical exercise with aesthetic or addictive purposes has increased, as well as the popularity of gyms. Aim: To analyze the orthorexics behavior, to know the influence of gender on psychological behavior and to analyze eating habits in a sample practicing physical activity. Methods: Observational, descriptive and retrospective study in which an ad hoc questionnaire was performed, incorporating Adherence to Mediterranean diet test, the State-Trait Anger Expression Inventory (STAXI-2), Emotional Eater Questionnaire (EEQ) and adapted the Spanish version of the Multidimensional Body Self Relations Questionnaire (MBSRQ). Besides, anthropometric assessment was performed in each participant. Results: 264 subjects were included in the study (156 men), 35.9 years (± 11.1 years). With mean BMI of 23.8 kg/m2 (± 3.1 kg/m2 ) and total body fat percentage 20.8 (± 8.7%). The average score Adherence to the Mediterranean diet was 5.9 (± 2.4). Orthorexic and obsessive behaviors were found, and between genders for some markers studied. Conclusion: The habits analyzed show a tendency to body worship, closer to a pathological condition rather than to a healthy aspect, causing alterations on perception, that result in dieting and alterations such as eating disorders (AU)

[Nutritional and psychological habits in people who practice exercise]. / Hábitos alimentarios y psicológicos en personas que realizan ejercicio físico.

INTRODUCTION: The distorted body image has become a global problem. The thinness as a standard of beauty for women, and fitness for men, has been linked to an increase in eating behavior disorders. The physical exercise with aesthetic or addictive purposes has increased, as well as the popularity of gyms. AIM: To analyze the orthorexics behavior, to know the influence of gender on psychological behavior and to analyze eating habits in a sample practicing physical activity. METHODS: Observational, descriptive and retrospective study in which an ad hoc questionnaire was performed, incorporating Adherence to Mediterranean diet test, the State-Trait Anger Expression Inventory (STAXI-2), Emotional Eater Questionnaire (EEQ) and adapted the Spanish version of the Multidimensional Body Self Relations Questionnaire (MBSRQ). Besides, anthropometric assessment was performed in each participant. RESULTS: 264 subjects were included in the study (156 men), 35.9 years (± 11.1 years). With mean BMI of 23.8 kg/m2 (± 3.1 kg/m2) and total body fat percentage 20.8 (± 8.7%). The average score Adherence to the Mediterranean diet was 5.9 (± 2.4). Orthorexic and obsessive behaviors were found, and between genders for some markers studied. CONCLUSION: The habits analyzed show a tendency to body worship, closer to a pathological condition rather than to a healthy aspect, causing alterations on perception, that result in dieting and alterations such as eating disorders.

Introducción: La distorsión de la imagen corporal se ha convertido en un problema mundial. La delgadez como patrón de belleza para las mujeres, y la musculación para los hombres, se han relacionado con el incremento de los Trastornos de la Conducta Alimentaria (TCA). La práctica de ejercicio físico con fines estéticos o adictivos ha incrementado, así como la popularización de los gimnasios. Objetivos: Analizar los comportamientos ortoréxicos, conocer la influencia del género en los comportamientos psicológicos y analizar los hábitos de alimentación de una muestra que practica actividad física. Métodos: Estudio observacional, descriptivo y retrospectivo en el que se realizó un cuestionario ad hoc, incorporando el test de Adherencia a Dieta Mediterránea, el Inventario de Expresión de Ira Estado-Rasgo (STAXI-2), el Cuestionario de Comedor Emocional (EEQ) adaptado y la versión española del Multidimensional Body Self Relations Questionnaire (MBSRQ). Además se realizó una valoración antropométrica a cada participante. Resultados: 264 sujetos fueron incluidos en el estudio (156 hombres), de 35,9 años (±11,1 años). Con IMC medio de 23,8 kg/m2 (±3,1 kg/m2) y un porcentaje de grasa corporal total 20,8 (±8,7%). La puntuación media la Adherencia a la Dieta Mediterránea, fue 5,9 (±2,4). Se encontraron comportamientos de carácter ortorexico y obsesivo, y diferencias entre géneros, para algunos marcadores estudiados. Conclusiones: Los hábitos analizados ponen de manifiesto una tendencia al culto al cuerpo, más próximo al extremo patológico que al aspecto saludable, provocando alteraciones sobre la percepción, que traen como consecuencia la realización de dietas y la aparición de alteraciones como los TCA.

Angiopoietin-2 Serum Levels Improve Noninvasive Fibrosis Staging in Chronic Hepatitis C: A Fibrogenic-Angiogenic Link.

AIMS: Accurate liver fibrosis staging is crucial for the management of chronic hepatitis C (CHC). The invasiveness and cost burden of liver biopsy have driven the search for new noninvasive biomarkers of fibrosis. Based on the link between serum angiopoietin-1 and 2 levels and CHC progression, we aimed to determine the value of these angiogenic factors as noninvasive biomarkers of liver fibrosis. METHODS: Serum levels of angiopoietin-1 and -2 were measured by ELISA in 108 CHC patients who underwent pretreatment liver biopsy. The correlation between angiopoietins and clinical and demographic variables with liver fibrosis was analyzed by univariate regression. Significant factors were then subjected to multivariate analysis, from which we constructed a novel noninvasive liver fibrosis index (AngioScore), whose performance was validated in an independent series of 71 CHC patients. The accuracy of this model was compared with other documented fibrosis algorithms by De Long test. RESULTS: Angiopoietins correlated significantly with hepatic fibrosis; however, only angiopoietin-2 was retained in the final model, which also included age, platelets, AST, INR, and GGT. The model was validated and behaved considerably better than other fibrosis indices in discriminating all, significant, moderate and severe liver fibrosis (0.886, 0.920, 0.923). Using clinically relevant cutoffs, we classified CHC patients by discarding significant fibrosis and diagnosing moderate and severe fibrosis with greater accuracy, sensitivity, and specificity. CONCLUSIONS: Our novel noninvasive liver fibrosis model, based on serum angiopoietin-2 levels, outperforms other indices and should help substantially in managing CHC and monitoring long-term follow-up prognosis.

Preliminary evidence of sustained expression of angiopoietin-2 during monocyte differentiation in chronic hepatitis C.

BACKGROUND: Monocytes are essential precursors of antigen-presenting cells, such as macrophages and dendritic cells, and contribute to the pathogenesis of chronic inflammatory diseases and cancer. AIMS: As Tie2-expressing monocytes (TEMs) are increased in the peripheral blood of patients with chronic hepatitis C (CHC), we aimed to examine the expression of Tie2 and angiopoietins (Ang1 and Ang2) during monocyte differentiation and maturation in CHC. METHODS: The expression of Tie2, CD11b, CD80, CD83, CD86 and MHC-II was measured by flow cytometry in peripheral blood monocytes and monocytes-derived cells (Mo-DCs) from nine healthy subjects and eight CHC patients whose HCV infection was unresolved after combination therapy. Ang1 and Ang2 levels were measured in cellular supernatants by ELISA. RESULTS: Mo-DCs from CHC patients expressed differential patterns of maturation markers compared with controls--primarily with regard to CD80. Tie2 was downregulated during monocyte differentiation in controls and CHC patients, whereas Ang1 expression was constant. However, Ang2 levels fell significantly during the differentiation of control monocytes, in contrast with those from CHC patients in whom Ang2 expression remained stable throughout differentiation. CONCLUSIONS: Altered expression of the Ang/Tie2 system in monocytes and Mo-DCs from CHC patients might account for the inflammatory and angiogenic disorders that are related to CHC. An increased understanding of Ang/Tie2 system regulation might be helpful in designing strategies to prevent CHC progression.

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

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.

Evaluation of chromogranin A determined by three different procedures in patients with benign diseases, neuroendocrine tumors and other malignancies.

UNLABELLED: CgA is a tumor marker in NET's (neuroendocrine tumors) but different ranges of sensitivity and specificity according to the commercial assay kits used have been reported. Our aim was to compare three commercial available assay kits that use three different methodologies (IRMA, RIA and ELISA) to determine CgA, in a clinical setting: 52 healthy people, 98 patients with benign diseases, 94 patients with non-NET´s malignancies, 20 SCLC and in 79 patients with NET's. RESULTS: Using a cut-off with a 100% specificity in healthy people (6 nmol/L, 60 ng/ml, and 90 ng/ml, for RIA, ELISA and IRMA, respectively), abnormal serum concentrations of CgA were found in a high proportion of patients with renal failure (76.7% ,86,7% and 93.3% with ELISA; IRMA and RIA, respectively) other benign diseases (excluding patients with creatinine concentrations > 1.5 mg/dl)(40,3%, 50% and 53,2% with ELISA, IRMA and RIA, respectively) or in patients with non-NET´s malignancies (excluding SCLC and patients with renal failure) (59,8% ELISA, 55,4%% IRMA, 37% RIA). The highest CgA sensitivity in SCLC was obtained with ELISA (100%) and in NET´s with ELISA (83.3%) and IRMA (80.3%) (RIA 65.2%). ROC curves comparing healthy people and NET´s or NET´s- benigns showed a significantly higher area under the curve (AUC) with ELISA (0.964 and 0.774), or IRMA (0.955 and 0.785), and smaller with RIA (0,806 and 0.691). CONCLUSIONS: CgA is not a specific tumormarker and abnormal concentrations may be found in non-NET´s. The higher AUC, sensitivity and specificity obtained with the ELISA and IRMA indicates that these are the best techniques to determine CgA.

Levelling profiles and a GPS network to monitor the active folding and faulting deformation in the Campo de Dalias (Betic Cordillera, southeastern Spain).

The Campo de Dalias is an area with relevant seismicity associated to the active tectonic deformations of the southern boundary of the Betic Cordillera. A non-permanent GPS network was installed to monitor, for the first time, the fault- and fold-related activity. In addition, two high precision levelling profiles were measured twice over a one-year period across the Balanegra Fault, one of the most active faults recognized in the area. The absence of significant movement of the main fault surface suggests seismogenic behaviour. The possible recurrence interval may be between 100 and 300 y. The repetitive GPS and high precision levelling monitoring of the fault surface during a long time period may help us to determine future fault behaviour with regard to the existence (or not) of a creep component, the accumulation of elastic deformation before faulting, and implications of the fold-fault relationship.

Hepatitis B virus promotes angiopoietin-2 expression in liver tissue: role of HBV x protein.

The progression of chronic hepatitis B (CHB) is related to fibrosis and to the emergence of intrahepatic anomalous vascular structures. Hepatitis B virus (HBV) X protein transactivator (HBx) may play a significant role in both processes. To analyze how HBV induces vascular growth and remodeling in vivo, we assessed the expression of angiopoietin-2 (Ang2) in liver biopsies from CHB patients by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry because of the relevant role of Ang2 in vascular development, remodeling, and tumor promotion. In addition, we analyzed the influence of HBx in the expression of Ang2 in HBx-expressing hepatocyte cell lines and in hepatic stellate cells stimulated with conditional medium from HBx-hepatocytes. Ang2 expression was clearly up-regulated at both mRNA and protein levels in the liver of CHB patients, showing an intense staining of inflammatory infiltrates and vascular structures at inflamed portal areas. HBx-expressing hepatocytes and stimulated stellate cells showed a significant induction of Ang2 expression. PI3K inhibitor and antioxidants repressed the 64-kd Ang2 form but further enhanced the inflammation-related 50-kd molecular species. Therefore, HBx could account for the induction of Ang2 observed in CHB, especially the 50-kd form, contributing to pathological angiogenesis and hepatocellular carcinoma progression.

The potential of angiogenesis soluble markers in chronic hepatitis C.

Angiogenesis, the formation of new vessels, has been reported to play a significant pathogenic role in liver damage-associated hepatitis C virus infection. Most of our current knowledge derives from immunohistochemical studies of hepatic biopsy samples obtained from chronic hepatitis C (CHC) patients. We evaluated whether CHC is associated with elevated serum levels of angiogenesis markers and whether these are modulated by therapy. Vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and soluble Tie-2 (sTie-2) were determined in the serum of 36 CHC patients, before and after receiving antiviral combination therapy with pegylated interferon alpha-2b plus ribavirin, and in 15 healthy controls. CHC patients showed elevated baseline VEGF and Ang-2 levels. After treatment, both factors were decreased, whereas antiangiogenic sTie-2 was increased, indicating a shift toward an "anti-angiogenic" profile of serum markers in CHC patients. In conclusion, this suggests that serum VEGF, Ang-2, and sTie-2 levels could be useful as noninvasive, mechanistically based markers of response to therapy and disease progression in CHC.

The prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma.

AIM: Lymphomagenesis is a multifactorial process in which genetic, environmental and infectious factors can be involved. The aim of the present study was to assess the prevalence of hepatitis C virus (HCV) infection among patients with non-Hodgkin's lymphoma (NHL), and to compare it with that of a control group of voluntary blood donors. METHODS: All consecutive patients with a histological diagnosis of NHL from January 1996 to December 2001 were included in this prospective study. As control group for HCV infection, voluntary blood donors recruited over the same time period from the same geographical area were considered. The presence of anti-HCV antibodies was investigated by ELISA-II and RIBA-II, and viraemia (HCV RNA) was tested by using a polymerase chain reaction (PCR). HCV genotyping was also performed. RESULTS: Ninety-nine patients (mean age 48 years) with NHL were diagnosed during the study period. Histological classification of NHL was high-intermediate grade (63 patients), and low grade (36 patients). Immunophenotype distribution was type B (86 patients) and type T (13 patients). Seven of the 99 NHL patients (7%) were infected with HCV (both using serology and PCR), five of them with immunophenotype B and two with immunophenotype T. The prevalence of HCV infection according to NHL phenotype was 5.8% in B-cell NHL and 15.4% in T-cell NHL. The HCV genotype was 1b in six cases, and 3a in one. In voluntary blood donors (mean age 45 years), HCV infection was detected in 517/55 587 (0.93%). Therefore, HCV infection was more frequent in NHL patients than in controls (odds ratio = 8.1; 95% CI = 3.7-17.6). The odds ratio for the association of HCV and B-cell NHL was 6.2 (95% CI = 2.5-15.3), and for T-cell NHL 16.4 (95% CI = 3.7-72.8). CONCLUSION: The prevalence of HCV infection in patients with NHL (both B- and T-type) is higher than that observed in controls, suggesting a role of HCV in lymphoma aetiopathogenesis.

Enhanced intrahepatic inducible nitric oxide synthase expression and nitrotyrosine accumulation in primary biliary cirrhosis and autoimmune hepatitis.

BACKGROUND/AIMS: Nitrosative stress resulting from increased nitric oxide (NO) synthesis contributes to the pathogenesis of chronic inflammatory diseases, including chronic viral hepatitis. Our goal was to assess the expression of inducible nitric oxide synthase (iNOS) and the formation of nitrotyrosine (NTY), as a marker of nitrosative stress, in liver biopsies from primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) patients. METHODS: Intrahepatic expression of iNOS and NTY was measured immunohistochemically and compared to histological scores of the severity of liver disease. RESULTS: Hepatocellular iNOS expression was observed in liver sections from PBC patients (with a diffuse lobular distribution) and from AIH patients (marked staining in areas of pronounced inflammation and necrosis), but not in control liver sections, including non-autoimmune cholestatic liver disease. Liver samples from PBC and AIH patients, but not from controls, showed NTY accumulation in clusters of hepatocytes and Kupffer cells. Increased iNOS expression and NTY accumulation correlated with the histological severity of PBC or AIH, especially with the degree of inflammation. CONCLUSIONS: Patients with PBC and AIH showed an enhanced intrahepatic iNOS expression and NTY accumulation, related to the histological severity of liver disease, consistent with NO-mediated nitration of hepatocellular proteins contributing to liver damage in both diseases.

Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty.

BACKGROUND: The Peptide YY (PYY) secretion pattern was assessed in morbidly obese (MO) patients before and after vertical banded gastroplasty (VBG). METHODS: 12 MO patients (10 women, 2 men) age 29-62 years, BMI 50.7 +/- 9.6 kg/m2, treated with a VBG were studied. Before surgery, blood samples were taken in basal conditions of fasting and 10, 15, 20, 30 and 60 min after the ingestion of a semiliquid test meal. This was repeated in the same patients 6 and 12 months after VBG. Blood samples were also taken from 6 healthy non-obese subjects as controls. PYY plasma concentration was measured by radioimmunoassay with I125. RESULTS: There were statistically significant differences between the preoperative PYY concentration in MO patients compared to controls. After a VBG, PYY concentration varied significantly compared to the preoperative levels. There was no significant difference between the PYY concentrations in the MO patients after VBG and the controls. CONCLUSION: PYY concentration is lower in MO patients compared with non-obese. After VBG, PYY concentration gradually rises to the control levels.