Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis.

Background: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. Patients and methods: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. Results: Three Crohn¿s disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. Conclusions: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.

RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection

Objective: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccinedemonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. Design: P. falciparum DNA from isolates collected during the trial was used for genotype studies. Setting: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. Participants: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. Outcome: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. Results: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at studymonth 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p 1/4 0.035, p 1/4 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p 1/4 0.478). Conclusions: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections.

Aeromonas surface glucan attached throught the O-antigen ligase represents a new way to obtain UDP-Glucose

We previously reported that A. hydrophila GalU mutants were still able to produce UDP-glucose introduced as a glucose residue in their lipopolysaccharide core. In this study, we found the unique origin of this UDP-glucose from a branched α-glucan surface polysaccharide. This glucan, surface attached through the O-antigen ligase (WaaL), is common to the mesophilic Aeromonas strains tested. The Aeromonas glucan is produced by the action of the glycogen synthase (GlgA) and the UDP-Glc pyrophosphorylase (GlgC), the latter wrongly indicated as an ADP-Glc pyrophosphorylase in the Aeromonas genomes available. The Aeromonas glycogen synthase is able to react with UDP or ADP-glucose, which is not the case of E. coli glycogen synthase only reacting with ADP-glucose. The Aeromonas surface glucan has a role enhancing biofilm formation. Finally, for the first time to our knowledge, a clear preference on behalf of bacterial survival and pathogenesis is observed when choosing to produce one or other surface saccharide molecules to produce (lipopolysaccharide core or glucan).

Distortion of surface groups in Cat (0) free-by-cyclic groups

Given a non-positively curved 2-complex with a circle-valued Morse function satisfying some extra combinatorial conditions, we describe how to locally isometrically embed this in a larger non- positively curved 2-complex with free-by-cyclic fundamental group. This embedding procedure is used to produce examples of CAT(0) free-by-cyclic groups that contain closed hyperbolic surface subgroups with polynomial distortion of arbitrary degree. We also produce examples of CAT(0) hyperbolic free-by-cyclic groups that contain closed hyperbolic surface subgroups that are exponentially distorted.

A topological proof that surface relators are test words

Vegeu el resum a l'inici del document del fitxer adjunt.

A proof that all Seifert 3-manifold groups and all virtual surface groups are conjugacy separable

We prove that the fundamental group of any Seifert 3-manifold is conjugacy separable. That is, conjugates may be distinguished infinite quotients or, equivalently, conjugacy classes are closed in the pro-finite topology.

Addressing Sea Surface Salinity retrieval at different spatial resolution. Feasibility study using OCCAM data within SEPS simulator and L2 processor tools

Projecte de recerca elaborat a partir d’una estada a la National Oceanography Centre of Southampton (NOCS), Gran Bretanya, entre maig i juliol del 2006. La possibilitat d’obtenir una estimació precissa de la salinitat marina (SSS) és important per a investigar i predir l’extensió del fenòmen del canvi climàtic. La missió Soil Moisture and Ocean Salinity (SMOS) va ser seleccionada per l’Agència Espacial Europea (ESA) per a obtenir mapes de salinitat de la superfície marina a escala global i amb un temps de revisita petit. Abans del llençament de SMOS es preveu l’anàlisi de la variabilitat horitzontal de la SSS i del potencial de les dades recuperades a partir de mesures de SMOS per a reproduir comportaments oceanogràfics coneguts. L’objectiu de tot plegat és emplenar el buit existent entre les fonts de dades d’entrada/auxiliars fiables i les eines desenvolupades per a simular i processar les dades adquirides segons la configuració de SMOS. El SMOS End-to-end Performance Simulator (SEPS) és un simulador adhoc desenvolupat per la Universitat Politècnica de Catalunya (UPC) per a generar dades segons la configuració de SMOS. Es va utilitzar dades d’entrada a SEPS procedents del projecte Ocean Circulation and Climate Advanced Modeling (OCCAM), utilitzat al NOCS, a diferents resolucions espacials. Modificant SEPS per a poder fer servir com a entrada les dades OCCAM es van obtenir dades de temperatura de brillantor simulades durant un mes amb diferents observacions ascendents que cobrien la zona seleccionada. Les tasques realitzades durant l’estada a NOCS tenien la finalitat de proporcionar una tècnica fiable per a realitzar la calibració externa i per tant cancel•lar el bias, una metodologia per a promitjar temporalment les diferents adquisicions durant les observacions ascendents, i determinar la millor configuració de la funció de cost abans d’explotar i investigar les posibiltats de les dades SEPS/OCCAM per a derivar la SSS recuperada amb patrons d’alta resolució.

What is the Jacobian of a Riemann surface with boundary?

We define the Jacobian of a Riemann surface with analytically parametrized boundary components. These Jacobians belong to a moduli space of "open abelian varieties" which satisfies gluing axioms similar to those of Riemann surfaces, and therefore allows a notion of "conformal field theory" to be defined on this space. We further prove that chiral conformal field theories corresponding to even lattices factor through this moduli space of open abelian varieties.

Paper dels exosomes en la comunicació entre cèl•lules presentadores d'antigen

Projecte de recerca elaborat a partir d’una estada al Institut Gustave-Roussy, França, entre febrer i març del 2007. L'objectiu principal del projecte consisteix en estudiar la interacció dels exosomes , obtinguts a partir d'un model in vitro com són les cél•lules dendrítiques derivades de monòcits, amb els subtipus de cel•lules dendrítiques mieloides i plasmacitoides, valorant la seva capacitat de captació i evaluant els canvis fenotípics i funcionals per part de les cèl•lules diana.

Desenvolupament de vacunes peptídiques y dendrímers basats en polietilenglicol per al tractament del càncer

El principal problema de les teràpies actuals contra el càncer es la baixa especificitat envers les cèl•lules tumorals, cosa que comporta gran quantitat d’efectes secundaris. Per això es important el desenvolupament de nous tipus de teràpies i sistemes d’alliberament efectius per als fàrmacs ja existents al mercat. En la immunoteràpia contra el càncer es pretén estimular el sistema immunològic per a eliminar les cèl•lules canceroses de manera selectiva. En aquest projecte s’han sintetitzat derivats de l’antigen peptídic de melanoma NY-ESO1 i s’ha estudiat la seva capacitat per a estimular el sistema immunològic com a vacunes contra el càncer. També s’han encapsulat el antígens peptídics en liposomes com a adjuvants i sistemes d’alliberament. De totes les variants peptídiques la que resultà més immunogènica fou la que contenia el grup palmitoil i el fragment toxoide tetànic en la seva estructura. La utilització de liposomes com a sistema adjuvant sembla una estratègia interessant per al disseny de vacunes contra el càncer donat que l’encapsulació del pèptid en liposomes va augmentar notablement la resposta immunològica de l’antigen. Per altra banda, s’han desenvolupat dendrímers basats en polietilenglicol com a sistemes alliberadors de fàrmacs per al tractament de tumors. El polietilenglicol és àmpliament utilitzat com a sistema d’alliberament de fàrmacs degut a les seves interessants propietats, augment de la solubilitat i dels temps de residència en plasma, entre d’altres. La metodologia química descrita permet la diferenciació controlada de varies posicions en la superfície del dendrímer a més del creixement del dendrímer fins a una segona generació. S’ha sintetitzat la primera generació del dendrímer contenint el fàrmac antitumoral 5-fluorouracil i s’han realitzat estudis de citotoxicitat comprovant que l’activitat del nanoconjugat és del mateix ordre de magnitud que el 5-fluorouracil sense conjugar.