Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-β and VEGF

OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

El Open Journal Systems en la Universidade de São Paulo: la experiencia de gestión del Portal de Revistas da USP

El objeto de este poster es presentar la experiencia de manejamiento de un portal de revistas científicas de acceso abierto, en una universidad pública y que integra los editores científicos, profesores y bibliotecarios. Iniciativas de esta naturaleza tienen importancia estratégica para la consolidación y el fortalecimiento del Movimiento de Acceso Abierto en los países en desarrollo, puesto que ofrecen la oportunidad de se vivir plenamente una cultura de acceso abierto en todas las etapas de certificación del conocimiento. La experiencia de la Universidade de São Paulo, se convierte en relevante, ya que promueve la integración de los diversos actores involucrados en la producción de revistas científicas. El Portal de Revistas da USP (http://www.revistas.usp.br), lanzado en 2008, es una iniciativa del Departamento Técnico do Sistema Integrado de Bibliotecas de USP que tiene el Programa de Apoio às Publicações Científicas Periódicas da USP. Esta iniciativa, basada en los principios del Movimiento de Acceso Abierto, tiene como objetivo promover la visibilidad y la accesibilidad de las revistas científicas publicadas oficialmente por la USP. Considerase que las revistas cumplen con un doble papel, como objeto y también vehículo de comunicación. Con esto las inversiones para calificación de las revistas incluyen recursos informáticos para garantizar la interoperabilidad entre distintos sistemas de información (bases de datos, catálogos, repositorios etc.), sistemas de gestión editorial en línea (para agilizar la tramitación de los manuscritos y la disminución de la publicación); la formación de los equipos (técnicos y bibliotecarios), atribuición de nomes DOI (digital object identifier), software de verificación de plágio. En 2012 se cambió el software de gestión del Portal para Open Journal Systems - OJS por lo cual se reunió por la primera vez, en um mismo dominio web las revistas científicas editadas en USP. De las más de 100 revistas publicadas en el Portal 29 están en DOAJ, 27 en SciELO Brasil, 20 en Scopus, 11 en JCR entre outros. En el Portal hay revistas con distintos perfiles, unas más institucionales y otras de calidad internacional. Algunas revistas más antíguas y consolidadas se utilizan de distintos sistemas de gestión de los manuscriptos y en el Portal es como un espejo para garantizar la presencia en la Universidad. Con tantas y tan distintas publicaciones el OJS se presenta como una promisora herramienta para la gestión del Portal de Revistas. El OJS surge como un sistema para la gestión individual de revistas científicos y con los avances de las tecnologías y principalmente del uso por la comunidad se conviertió en herramienta de gestión de Portal. Para una mejor gestión del Portal se presenta algunas recomendaciones, basadas en la experiencia, y que podrán mejorar el trabajo de gestión del conjunto de las revistas: en la pantalla de creación de revistas se deberá incluir todos los datos del registro oficial en ISSN, sin posibilidad de edición por los editores-gerentes; en el listado general de revistas se podría incluir una indicación de las revistas que están en línea y las que están aún en configuración; clara identificación de las revistas vigentes y no-vigentes, una vinculación mas clara de las revistas que cambiaran su título y que están vigentes; una tabla para selección de fuentes de indización; edición de contenidos ya publicados solamente por el administrador del sistema; gestión centralizada del DOI y de la preservación digital en LOCKSS y un painel con los datos estadísticos (total de revistas, ediciones, estatísticas Counter, autores etc). Además el fortalecimiento y creación de centros de desarrollo de OJS en las Universidades Latinoamericanas podría impulsionar el uso del sistema en su totalidad por los editores de la región.

Portal de Busca Integrada do SIBiUSP: metodologia de implantação

Relata o estudo, a instalação e implantação de ferramenta de descoberta e entrega do Portal de Busca Integrada, para o Sistema Integrado de Bibliotecas da Universidade de São Paulo (SIBiUSP). Esta nova interface denominada Portal de Busca Integrada possibilita uma nova experiência de pesquisa científica ao usuário final pela recuperação de literatura em diferentes fontes de informação.

Portal de revistas da USP

O Portal de Revistas da USP apresenta-se como uma estratégia do Sistema Integrado de Bibliotecas, por meio de seu Programa de Apoio às Publicações Científicas Periódicas, para aumentar a visibilidade e acessibilidade das revistas científicas da Universidade de São Paulo. Para fazer parte deste Programa as revistas devem cumprir com critérios de qualidade, definidos por uma Comissão de Credenciamento, formada por professores e bibliotecários, e pautados em padrões internacionais. Atualmente 62 publicações estão credenciadas neste Programa.

Portal de Accesibilidad y Comunicación

[ES]La educación inclusiva surge del convencimiento de que el derecho a la educación es un derecho universal que está en la base de una sociedad más justa. Uno de los ejes de este tipo de educación, entre otros, es la creación de entornos universales adaptados, e implica el acceso en condiciones de igualdad a una educación de calidad. En un campus inclusivo la herramienta on-line: PORTAL DE ACCESIBILIDAD Y COMUNICACIÓN (PAC) es una estrategia para la participación de la comunidad universitaria en donde cualquiera de sus miembros puede valorar la aplicación de las normas vigentes en materia de accesibilidad universal y proponer mejoras. La Universidad está llamada a ser un referente en la asunción de los derechos humanos, promoción del voluntariado y la no discriminación.

Transformations of bridging ligands in diiron complexes: unconventional routes to new functionalized multisite bound organic frames

The main scope of this Ph.D. thesis has concerned the possible transformations of bridging ligands in diiron complexes, in order to explore unconventional routes to the synthesis of new functionalized multisite bound organic frames. The results achieved during the Ph.D. can be summarized in the following points: 1) We have extended the assembling between small unsaturated molecules and bridging carbyne ligands in diiron complexes to other species. In particular, we have investigated the coupling between olefins and thiocarbyne, leading to the synthesis of thioallylidene bridging diiron complexes. Then, we have extended the study to the coupling between olefins and aminocarbyne. This result shows that the coupling between activated olefins and heteroatom substituted bridging carbynes has a general character. 2) As we have shown, the coupling of bridging alkylidyne ligands with alkynes and alkenes provides excellent routes to the synthesis of bridging C3 hydrocarbyl ligands. As a possible extension of these results we have examined the synthesis of C4 bridging frames through the combination of bridging alkylidynes with allenes. Also in this case the reaction has a general character. 3) Diiron complexes bearing bridging functionalized C3 organic frames display the presence of donor atoms, such as N and S, potentially able to coordinate unsaturated metal fragments. Thus, we have studied the possibility for these systems to act as ‘organometallic ligands’, in particular towards Pd and Rh. 4) The possibility of releasing the organic frame from the bridging coordination appears particularly appealing in the direction of a metal-assisted organic synthesis. Within this field, we have investigated the possibility of involving the C3 bridging ligand in cycloaddition reactions with alkynes, with the aim of generating variously functionalized five-membered cycles. The [3+2] cyclization does not lead to the complete release of the organic fragment but rather it produces its transformation into a cyclopentadienyl ring, which remains coordinated to one Fe atom. This result introduces a new approach to the formation of polyfunctionalised ferrocenes. 5) Furthermore, I have spent a research period of about six months at the Department of Inorganic Chemistry of the Barcelona University, under the supervision of Prof. Concepción López, with the aim of studying the chemistry of polydentate ferrocenyl ligands and their use in organometallic synthesis.

Evaluation of the effects of insertion of viscous dampers in Moment Resisting Frames

This research work faces the problem of insertion of viscous dampers into Moment Resisiting Frames (MRF) for maximum efficiency in mitigation of the seismic effects. The work would lead to a precise design indication. The fundamental result of the thesis consists in showing that, even for moment-resisting structures, you can design a system of added viscous dampers able to achieve target levels of performances. Ie given the reduction factor in the seismic response, discover the characteristics of the viscous dampers which allow to achieve it.

Portal hypertension: a comparison between portal-venous pressure measurement and ARFI measurement of liver and spleen stiffness

PURPOSE. Portal pressure is measured invasively as Hepatic Venous Pressure Gradient (HVPG) in the angiography room. Liver stiffness measured by Fibroscan was shown to correlate with HVPG values below 12 mmHg. This is not surprising, since in cirrhosis the increase of portal pressure is not directly linked with liver fibrosis and consequently to liver stiffness. We hypothesized that, given the spleen’s privileged location upstream to the whole portal system, splenic stiffness could provide relevant information about portal pressure. Aim of the study was to assess the relationship between liver and spleen stiffness measured by Virtual Touch™ (ARFI) and HVPG in cirrhotic patients. METHODS. 40 consecutive patients (30 males, mean age 62y, mean BMI=26, mean Child-Pugh A6, mean platelet count=92.000/mmc, 19 HCV+, 7 with ascites) underwent to ARFI stiffness measurement (10 valid measurements in right liver lobe both surface and centre, left lobe and 20 in the spleen) and HPVG, blindly to each other. Median ARFI values of 10 samplings on every liver area and of 20 samplings on spleen were calculated. RESULTS. Stiffness could be easily measured in all patients with ARFI, resulting a mean of 2,61±0,76, 2,5±0,62 and 2,55±0,66 m/sec in the liver areas and 3.3±0,5 m/s in the spleen. Median HPVG was 14 mmHg (range 5-27); 28 patients showed values ≥10 mmHg. A positive significant correlation was found between spleen stiffness and HPVG values (r=0.744, p<0.001). No significant correlation was found between all liver stiffness and HVPG (p>0,05). AUROC was calculated to test spleen stiffness ability in discriminating patients with HVPG ≥10. AUROC = 0.911 was obtained, with sensitivity of 69% and specificity of 91% at a cut-off of 3.26 m/s. CONCLUSION. Spleen stiffness measurement with ARFI correlates with HVPG in patients with cirrhosis, with a potential of identifying patients with clinically significant portal hypertension.

Evoluzione tecnologica in ambito End User Computing: un caso d'uso basato su Horizon Workspace Portal

L'obbiettivo del progetto di cui tratta questa tesi è costituire un ambiente intuitivo e facilmente utilizzabile dall'utente finale che permetta di accedere sia alle applicazioni aziendali sia ai desktop virtuali da qualsiasi dispositivo effettui l'accesso. Grazie alle recenti tecnologie di End User Computing messe a disposizione da VMware è possibile virtualizzare qualsiasi applicazione Windows e renderla disponibile tramite Internet a qualsiasi utente la richieda, indifferentemente dal sistema operativo o dal luogo in cui si trova. Il progetto descritto nella tesi spiega come implementare tale ambiente tramite il prodotto Horizon Workspace Portal integrato nella suite Horizon 6.

NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study

NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension.

Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats

We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

A transgenic model for conditional induction and rescue of portal hypertension reveals a role of VEGF-mediated regulation of sinusoidal fenestrations

Portal hypertension (PH) is a common complication and a leading cause of death in patients with chronic liver diseases. PH is underlined by structural and functional derangement of liver sinusoid vessels and its fenestrated endothelium. Because in most clinical settings PH is accompanied by parenchymal injury, it has been difficult to determine the precise role of microvascular perturbations in causing PH. Reasoning that Vascular Endothelial Growth Factor (VEGF) is required to maintain functional integrity of the hepatic microcirculation, we developed a transgenic mouse system for a liver-specific-, reversible VEGF inhibition. The system is based on conditional induction and de-induction of a VEGF decoy receptor that sequesters VEGF and preclude signaling. VEGF blockade results in sinusoidal endothelial cells (SECs) fenestrations closure and in accumulation and transformation of the normally quiescent hepatic stellate cells, i.e. provoking the two processes underlying sinusoidal capillarization. Importantly, sinusoidal capillarization was sufficient to cause PH and its typical sequela, ascites, splenomegaly and venous collateralization without inflicting parenchymal damage or fibrosis. Remarkably, these dramatic phenotypes were fully reversed within few days from lifting-off VEGF blockade and resultant re-opening of SECs' fenestrations. This study not only uncovered an indispensible role for VEGF in maintaining structure and function of mature SECs, but also highlights the vasculo-centric nature of PH pathogenesis. Unprecedented ability to rescue PH and its secondary manifestations via manipulating a single vascular factor may also be harnessed for examining the potential utility of de-capillarization treatment modalities.

Organizational Frames for Professional Claims: Private Military Corporations and the Rise of the Military Paraprofessional

Corporations, nongovernmental organizations, and other organizational forms are major players in the sodal world. Recently, sociological scholarship on organizations has converged with research on the professions to discuss the ways in which professions are shaped or influenced by different organizational forms. In this article, I borrows from the notion of framing within social movement research to argue that organizational forms frame the bids of aspiring professionals. More specifically, I argue that certain organizational forms-such as that of the modern corporation-can aid would-be professionals in making their claims for professional recognition. Organizations do this, I argue, by providing aspiring professionals with a ready-made setting, rationale, and guarantees that make the newcomers more easily recognizable as professionals to outside audiences. I explore this argument by examining how the corporate form has facilitated private military contractors in their attempts to legitimate and develop this highly controversial new industry. The data are drawn from my interviews with private military contractors, state officials, and other interested parties surrounding private military corporations, as well as from archival data that detail the rise of the private military industry.