Mobilization of xanthine oxidase from the gastrointestinal tract in acute pancreatitis

BACKGROUND: Xanthine oxidoreductase has been proposed to play a role in the development of local and systemic effects of acute pancreatitis. Under physiologic conditions, the enzyme exists mainly as xanthine dehydrogenase (XDH) but can be converted by proteolytic cleavage to its superoxide-generating form xanthine oxidase (XOD). In addition to its intracellular location XDH/XOD is also associated to the polysaccharide chains of proteoglycans on the external endothelial cell membrane. In the early stages of acute pancreatitis, this enzyme seems to be arising from its mobilization from the gastrointestinal endothelial cell surface. Taking into account the ability of α-amylase to hydrolyze the internal α-1,4 linkages of polysaccharides, we wanted to elucidate the involvement of α-amylase in XDH/XOD mobilization from the gastrointestinal endothelial cell surface and the relevance of the ascitic fluid (AF) as the source of α-amylase in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in male Wistar rats by intraductal administration of 5% sodium taurocholate. In another experimental group 3000 U/Kg α-amylase was i.v. administered. The concentrations of XDH, XOD and α-amylase in plasma and AF and myeloperoxidase (MPO) in lung have been evaluated. In additional experiments, the effect of peritoneal lavage and the absorption of α-amylase present in the AF by an isolated intestine have been determined. RESULTS: Similar increase in XDH+XOD activity in plasma was observed after induction of acute pancreatitis and after i.v. administration of α-amylase. Nevertheless, the conversion from XDH to XOD was only observed in the pancreatitis group. Lung inflammation measured as MPO activity was observed only in the pancreatitis group. In addition peritoneal lavage prevented the increase in α-amylase and XDH+XOD in plasma after induction of pancreatitis. Finally, it was observed that α-amylase is absorbed from the AF by the intestine. CONCLUSIONS: During the early stages of acute pancreatitis, α-amylase absorbed from AF through the gastrointestinal tract could interfere with the binding of XDH/XOD attached to glycoproteins of the endothelial cells. Proteolytic enzymes convert XDH into its oxidase form promoting an increase in circulating XOD that has been reported to be one of the mechanisms involved in the triggering of the systemic inflammatory process

Localized Populations of CD8low/− MHC Class I Tetramer+ SIV-Specific T Cells in Lymphoid Follicles and Genital Epithelium

CD8 T cells play an important role in controlling viral infections. We investigated the in situ localization of simian immunodeficiency virus (SIV)-specific T cells in lymph and genital tissues from SIV-infected macaques using MHC-class I tetramers. The majority of tetramer-binding cells localized in T cell zones and were CD8+. Curiously, small subpopulations of tetramer-binding cells that had little to no surface CD8 were detected in situ both early and late post-infection, and in both vaginally and rectally inoculated macaques. These tetramer+CD8low/− cells were more often localized in apparent B cell follicles relative to T cell zones and more often found near or within the genital epithelium than the submucosa. Cells analyzed by flow cytometry showed similar populations of cells. Further immunohistological characterization revealed small populations of tetramer+CD20− cells inside B cell follicles and that tetramer+ cells did not stain with γδ-TCR nor CD4 antibodies. Negative control tetramer staining indicated that tetramer+CD8low/− cells were not likely NK cells non-specifically binding to MHC tetramers. These findings have important implications for SIV-specific and other antigen-specific T cell function in these specific tissue locations, and suggest a model in which antigen-specific CD8+ T cells down modulate CD8 upon entering B cell follicles or the epithelial layer of tissues, or alternatively a model in which only antigen-specific CD8 T cells that down-modulate CD8 can enter B cell follicles or the epithelium

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Entrepreneurial intentions and entrepreneurship education to University students in Portugal

[EN] This article analyzes entrepreneurial intentions and motivations that encourage university students of Tourism to create their own company. Methodology is based on an empirical study, using a questionnaire adapted from a model of Veciana and Urbano (Actitudes de los estudiantes universitarios hacia la creación de empresas: un estudio empírico comparativo entre Catalunya y Puerto Rico. El emprendedor innovador y la creación de empresas de I + D + I, University of Valencia, pp 35 58, 2004), including the desirability and viability concepts. One hundred and sixty students answered the questionnaire from a total study population of 243 official Tourism degree students of the Superior Institute of Accounting and Management of Porto. This research finds out that the university students have a very positive perception about the desire to create their own company; a 90 % of students express their desire to do it, and 83.5 % express their intention. Moreover, a 57.5 % think that within actual crisis it is more difficult to do than before it. This research lets us get an in-depth study of a student of Tourism degree, finding out his entrepreneurial attitudes. It can be the first step to wake up and encourage students interest for starting up their own business.Del Rio-Rama, MDLC.; Peris-Ortiz, M.; Álvarez García, J.; Rueda Armengot, C. (2016). Entrepreneurial intentions and entrepreneurship education to University students in Portugal. Technology, Innovation and Education. 2(7):1-11. doi:10.1186/s40660-016-0013-5S11127Ajzen I (1991) The theory of plannes behavior. Organ Behav Hum Decis Process 50:179–211Aponte M (2002) Factores condicionantes de la creación de empresas en Puerto Rico: un enfoque institucional. Doctoral dissertation, Autonomous University of BarcelonaAponte M, Urbano D, Veciana JM (2006) Actitudes hacia la creación de empresas: un estudio comparativo entre Catalunya y Puerto Rico. Centro de Investigaciones Comerciales e Iniciativas Académicas de la Facultad de Administración de Empresas. Forum Empresarial 11(2):52–75Bae TJ, Qian S, Miao C, Fiet JO (2014) The relationship between entrepreneurship education and entrepreneurial intentions: a meta-analytic review. Entrep Theory Pract 38(2):217–254Brice J (2004) The role of personality dimensions on the formation of entrepreneurial intentions. USASBE Small Business Advancement National Center. University of Central Arkansas, USACabana-Villca R, Cortes-Castillo I, Plaza-Pasten D, Castillo-Vergara M, Alvarez-Marin A (2013) Análisis de las capacidades emprendedoras potenciales y efectivas en alumnos de centros de educación superior. J Technol Manag Innov 8(1):65–75Davidsson P (1989) Continued entrepreneurship and small firm business. Stockholm School of Economics, StockholmDavidsson P (1995) Culture, structure and regional levels of entrepreneurship. Entrep Reg Dev 7(1):41–62De Jorge-Moreno J, Castillo LL, Triguero MS (2012) The effect of business and economics education programs on students’ entrepreneurial intention. Eur J Train Dev 36(4):409–425Díaz JC, Hernández RM, Barata ML (2007) Estudiantes universitarios y creación de empresas. Un análisis comparativo entre España y Portugal. In Ayala, J.C. (coord.) Conocimiento, innovación y emprendedores: camino al futuro. Grupo FEDRA, MadridDo Paço AMF, Ferreira JM, Raposo M, Rodrigues RG, Dinis A (2011) Behaviours and entrepreneurial intention: empirical findings about secondary students. J Int Entrep 9(1):20–38Dohse D, Walter SG (2010) The role of entrepreneurship education and regional context in forming entrepreneurial intentions (No. 2010, 18). Document de treball de l’IEBEuropean Commission (2006). Entrepreneurship education in Europe: Fostering entrepreneurial mindsets through education and learning, Final Proceedings of the Conference on Entrepreneurship Education in OsloEurostat (2014) Informes sobre el empleo en la Unión Europea. Available in: http://europa.eu/publications/statistics/index_es.htmFuentes F, Saco F, Rodríguez P (2013) Estudio sobre el perfil emprendedor en el alumnado universitario de Córdoba. UCO Consejo Social de la Universidad de Córdoba, III Edición, Córdoba, pp 1–180Fuentes García FJ (2007) Análisis del Perfil Emprendedor del alumnado universitario y preuniversitario de Córdoba. Consejo Social Universidad de Córdoba, pp 1–105Genesca Garrigosa E, Veciana Verges JM (1984) Actitudes hacia la creación de empresas. Información Comercial Española 611:147–155Gerba DT (2012) Impact of entrepreneurship education on entrepreneurial intentions of business and engineering students in Ethiopia. Afr J Econ Manag Stud 3(2):258–277Gorman G, Hanlon D, King W (1997) Some research perspectives on entrepreneurship education and education for small business management: a ten-year literature review. Int Small Bus J 15(3):56–77Guerrero M, Rialp J, Urbano D (2008) The impact of desirability and feasibility on entrepreneurial intentions: a structural equation model. Int Entrep Manag J 4(1):35–50Haynie JM, Shepherd DA, McMullen JS (2009) An opportunity for me? The role of resources in opportunity evaluation decisions. J Manage Stud 46(3):337–361Hernangomez J, Martín N, Rodriguez AI, Saboia F (2005) El emprendedor nace o se hace? Un análisis de los determinantes del espíritu emprendedor. XVI Spanish-Portuguese Meeting of Scientic Management. Sevilla:33–44Hmieleski KM, Corbett AC (2006) Proclivity for improvisation as a predictor of entrepreneurial intentions. J Small Bus Manage 44(1):45–63Honjo Y (2004) Growth of new start-up firms: evidence from the Japanese manufacturing industry. Appl Econ Lett 11(1):21–32Hyde GC (1989) The relationship between policy and research. In Rosa, P.; Birley, S. Cannon, T. and O´Neill, K. The Role and Contribution of Small Business Research, Chap. 3:55–77, Institute ReportKolvereid L (1996) Prediction of employment status choice intentions. Entrep Theory Pract 21(1):47–57Kourilsky ML, Walstad WB (1998) Entrepreneurship and female youth: knowledge, attitude, gender differences, and educational practices. J Bus Ventur 13(1):77–88Krueger N, Brazeal D (1994) Entrepreneurial Potencial and Potencial Entrepreneurs. Entrep Theory Pract 18(3):91–104Krueger NF, Carsrud AL (1993) Entrepreneurial intentions: applying the theory of planned behaviour. Entrep Reg Dev 5(4):315–330Lanero A, Vázquez JL, Gutiérrez P, García MP (2011) The impact of entrepreneurship education in European universities: an intention-based approach analyzed in the Spanish area. Int Rev Public Nonprofit Marketin 8(2):111–130Miller BK, Bell JD, Palmer M, González A (2009) Predictors of entrepreneurial intentions: a quasi-experiment comparing students enrolled in introductory management and entrepreneurship classes. J Bus Entrep 21(2):39–62Neck HM, Zacharakis AL, Bygrave WD, Reynolds PD (2003) Global entrepreneurship monitor: 2002 executive report. Babson College, Babson, MANorth DC (1990) Institutions, Institutional Change and Economic Performance. Cambridge University Press, Cambridge (UK)North D (1993) Instituciones, cambio institucional y desempeño económico. Fondo de Cultura Económica, MéxicoNorth DC (2005) Understanding the Process of Economic Change. Academic Foundation. University Press, PrincentonGEM Portugal (2012) Estudo sobre o Empreendedorismo. Global Entrepreneruship Monitor (GEM). Instituto Universitário de Lisboa (ISCTEIUL) http://web.spi.pt/GEMportugal2012/files/GEM_PORTUGAL_2012.pdfRaposo M, do Paço A, Ferreira J (2008a) Entrepreneur’s profile: a taxonomy of attribu tes and motivations of university students. J Small Bus Enterp Dev 15(2):405–420Raposo MLB, Ferreira JJM, do Paço AMF, Rodrigues RJG (2008b) Propensity to firm creation: empirical research using structural equations. Int Entrep Manag J 4(4):485–504Robinson PB, Stimpson DV, Huefner JC, Hunt HK (1991) An attitude approach to the prediction of entrepreneurship. Entrep Theory Pract 15(4):13–31Samad Aghayi J (2008) Entrepreneurship organization. Public Administration Training Center Publications, TehranScherer RF, Adams JS, Carley S, Wiebe FA (1989) Role model performance effects on development of entrepreneurial career preference. Entrep Theory and Pract, spring:53–71Scherer RF, Brodzinski JD, Wiebe F (1991) Examining the relationship between personality and entrepreneurial career preference. 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Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation- associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%–36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or g-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter 280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-lowdensity lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Zoverexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosisinfo:eu-repo/semantics/publishedVersio

Immunogenic Profiling in Mice of a HIV/AIDS Vaccine Candidate (MVA-B) Expressing Four HIV-1 Antigens and Potentiation by Specific Gene Deletions

BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be relevant in protection against HIV-1 infection are still undefined. The highly attenuated poxvirus strain MVA is one of the most promising vectors to be use as HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV-1-specific immune responses in different animal models and gene signatures in human dendritic cells (DCs) with immunoregulatory function. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to characterize in more detail the immunogenic profile of MVA-B and to improve its immunogenicity we have generated a new vector lacking two genes (A41L and B16R), known to counteract host immune responses by blocking the action of CC-chemokines and of interleukin 1beta, respectively (referred as MVA-B DeltaA41L/DeltaB16R). A DNA prime/MVA boost immunization protocol was used to compare the adaptive and memory HIV-1 specific immune responses induced in mice by the parental MVA-B and by the double deletion mutant MVA-B DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment responsible for >91.9% of the total HIV-1 responses in both immunization groups. However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1-specific CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in both immunization groups. Significantly, while MVA-B induced preferentially Env-specific CD8(+) T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN-specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both vectors were capable of producing similar levels of antibodies against Env. CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B DeltaA41L/DeltaB16R induced in mice robust, polyfunctional and durable T-cell responses to HIV-1 antigens, but the double deletion mutant showed enhanced magnitude and quality of HIV-1 adaptive and memory responses. Our observations are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors as HIV-1 vaccines

Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker of replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV - related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.A detecção do genoma do HBV no soro por hibridização molecular é o mais sensível e específico marcador da replicação e infectividade do HBV, sendo sua utilização proposta como técnica rotineira no acompanhamento de doenças relacionadas a este vírus. Comparando diferentes técnicas descritas anteriormente, escolhemos a deposição direta das amostras séricas sobre a membrana de nitrocelulose sob filtração a vácuo, seguida de banhos desnaturantes e neutralisantes como mais prática e simples, com sensibilidade equivalente. O ensaio da DNA polimerase usando ácido fosfonofórmico como inibidor virai específico mostrou 86.8% de concordância com a detecção direta do DNA viral, sendo, portanto, uma alternativa viável no acompanhamento de pacientes com hepatite crônica B. Encontramos 19,2% das amostras AgHBe positivos sem outros marcadores de replicação viral. Por outro lado, nenhuma amostra anti-HBe positiva teve HBV-DNA detectável. Discordância entre estes dois sistemas foi extensamente descrita, e confirmamos pela primeira vez este fato em pacientes com hepatite crônica B em nosso país. Técnicas de biologia molecular são, portanto, fundamentais na determinação da replicação viral em cada paciente

Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF (vol 72, pg 688, 2020)

Cellular mechanisms in basic and clinical gastroenterology and hepatolog