Circulating Antigens Levels in Different Clinical Forms of the Schistosoma mansoni Infection

With the aim to evaluate the circulating cathodic antigen (CCA) levels in relation to the different clinical phases of Schistosoma sp. infection a sandwich ELISA using monoclonal antibody 5H11 was performed. The sera of three groups of 25 Brazilian patients with acute, intestinal and hepatosplenic forms of S. mansoni infection were tested and compared to a non-infected control group. Patients and control groups were matched for age and sex and the number of eggs per gram of feces was equally distributed among the three patient groups. Sensitivity of 100%, 72%, 52% of the assay was observed for the intestinal, hepatosplenic and acute toxemic groups respectively. The specificity was 100%. Intestinal and hepatosplenic groups presented CCA levels significantly higher in comparison to those observed for acute patients (F-ratio = 2,524; p = 0.000 and F-ratio = 6,314; p = 0.015 respectively). There was no significant difference of CCA serum levels between hepatosplenic and intestinal groups (F-ratio = 1,026; p = 0.316).

Análisis de las formas clínicas de uveítis asociadas a esclerosis múltiple. Revisión retrospectiva de los casos atendidos en el servicio de oftalmología del Hospital Universitario Vall d`Hebron

Objectiu: Analitzar les diferents formes clíniques d’uveïtis en pacients amb esclerosi múltiple (EM), el seu tractament i resultats. Mètode: Estudi retrospectiu de 18 pacients diagnosticats d’EM que van presentar episodis d’inflamació intraocular clínicament rellevants. Resultats: La forma clínica predominant va ser la uveïtis intermèdia (14 casos), seguida de la forma vasculítica (2 casos). El tractament mèdic va aconseguir una milloria global de 1’68 ± 1,47 línies de visió; mentre que la cirurgia va mostrar una milloria de 3,36 ± 2,46 línies de visió rere la facoemulsificació, i de 2,25 ± 0,56 línies de visió rere la vitrectomia. Conclusions: El tractament amb corticoides locals o sistèmics assoleix un adequat control de la majoria dels episodis d’inflamació intraocular. Els resultats de la cirurgia son molt satisfactoris en aquest grup de pacients, un cop controlats mèdicament els brots d’activitat inflamatòria intraocular.

Effects of a dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240, on endocrine and renal functions in healthy volunteers.

OBJECTIVE: To investigate the endocrine and renal effects of the dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240. DESIGN: A randomized, placebo-controlled, crossover study was performed in 12 healthy volunteers. METHODS: MDL 100,240 was administered intravenously over 20 min at single doses of 6.25 and 25 mg in subjects with a sodium intake of 280 (n = 6) or 80 (n = 6) mmol/day. Measurements were taken of supine and standing blood pressure, plasma angiotensin converting enzyme activity, angiotensin II, atrial natriuretic peptide, urinary atrial natriuretic peptide and cyclic GMP excretion, effective renal plasma flow and the glomerular filtration rate as p-aminohippurate and inulin clearances, electrolytes and segmental tubular function by endogenous lithium clearance. RESULTS: Supine systolic blood pressure was consistently decreased by MDL 100,240, particularly after the high dose and during the low-salt intake. Diastolic blood pressure and heart rate did not change. Plasma angiotensin converting enzyme activity decreased rapidly and dose-dependently. In both the high- and the low-salt treatment groups, plasma angiotensin II levels fell and renin activity rose accordingly, while plasma atrial natriuretic peptide levels remained unchanged. In contrast, urinary atrial natriuretic peptide excretion increased dose-dependently under both diets, as did urinary cyclic GMP excretion. Effective renal plasma flow and the glomerular filtration rate did not change. The urinary flow rate increased markedly during the first 2 h following administration of either dose of MDL 100,240 (P < 0.001) and, similarly, sodium excretion tended to increase from 0 to 4 h after the dose (P = 0.07). Potassium excretion remained stable. Proximal and distal fractional sodium reabsorption were not significantly altered by the treatment. Uric acid excretion was increased. The safety and clinical tolerance of MDL 100,240 were good. CONCLUSIONS: The increased fall in blood pressure in normal volunteers together with the preservation of renal hemodynamics and the increased urinary volume, atrial natriuretic peptide and cyclic GMP excretion distinguish MDL 100,240 as a double-enzyme inhibitor from inhibitors of the angiotensin converting enzyme alone. The differences appear to be due, at least in part, to increased renal exposure to atrial natriuretic peptide following neutral endopeptidase blockade.

Effects of physiological self-crowding of DNA on shape and biological properties of DNA molecules with various levels of supercoiling.

DNA in bacterial chromosomes and bacterial plasmids is supercoiled. DNA supercoiling is essential for DNA replication and gene regulation. However, the density of supercoiling in vivo is circa twice smaller than in deproteinized DNA molecules isolated from bacteria. What are then the specific advantages of reduced supercoiling density that is maintained in vivo? Using Brownian dynamics simulations and atomic force microscopy we show here that thanks to physiological DNA-DNA crowding DNA molecules with reduced supercoiling density are still sufficiently supercoiled to stimulate interaction between cis-regulatory elements. On the other hand, weak supercoiling permits DNA molecules to modulate their overall shape in response to physiological changes in DNA crowding. This plasticity of DNA shapes may have regulatory role and be important for the postreplicative spontaneous segregation of bacterial chromosomes.

Tratamiento de los hemangiomas infantiles con propranolol: estudio prospectivo abierto con 25 pacientes. Evolución y manejo”

Estudi observacional prospectiu obert sobre l’eficàcia del propranolol oral en 25 nens amb hemangiomes infantils que associen algun tipus de morbiditat. S’analitzen també els efectes secundaris, l’evolució de les lesions i les variables que influeixen en les recaigudes al finalitzar la medicació. L’estudi conclou que el propranolol és un fàrmac efectiu i ben tolerat en el tractament dels hemangiomes infantils. La duració del tractament és la única variable que demostra influir de forma estadísticament significativa en l’aparició de recidives al suspendre la medicació.

On the function of proton-gated ion channels ASICs and TRPV1 : a patch-clamp study

AbstractAcidosis is encountered during tissue inflammation and triggers pain in humans. H+-gated ion channels are expressed at high levels in sensory neurons of the peripheral nervous system. Ion channels from two different families present the required pH sensitivity to detect the acidosis associated with peripheral inflammation: Acid-Sensing Ion Channels (ASICs) and the Transient Receptor Potential Vanilloid-1 (TRPV1) channel.ASICs are members of the Degenerin/Epithelial Na+ Channel family of ion channels. Six ASIC subunits have been identified in mammals (ASICla, -lb, -2a, -2b, -3 and -4). ASICs form In-activated voltage-insensitive homo- or heterotrimeric Na+ channels. TRPV1 is a member of the TRP family of ion channels and forms non-selective cation channels that mediate a sustained current. TRPV1 is activated by H+, heat (T>43°C), lipids, capsaicin, voltage and other stimuli. A stimulus can increase TRPV1 response to a different stimulus. For example H+ can shift the capsaicin concentration dependence of TRPV1 to lower values. ASICs and TRPV1 have been shown to be involved in inflammatory pain. Using the patch-clamp technique, we studied different aspects of the function of ASICs and TRPV1 in the physiological context of pain.In the first part of this thesis, we characterize the effect of a temperature increase from 25 to 35°C on the function of ASICs and TRPV1 in transfected CHO cells and primary cultures of rat DRG sensory neurons. ASICs give rise to transient currents while TRPV1 mediates a sustained current. In addition, ASICs and TRPV1 respond to H+ with distinct pH dependences. We assess the relative contribution of ASICs and TRPV1 to H+-evoked electrical signaling in rat DRG neurons and we conclude that ASICs are the most important pH sensors in the pH range 7.4 to 6.0 at 35°C in sensory neurons.ASICs and TRPV1 are expressed in the epithelium lining the lumen of the bladder (urothelium). The Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) is a painful condition associated with a dysfunction of the urothelial barrier and with inflammation. In the second part of this thesis, we show that human urothelial cells -the cell line TEU2 and primary cultures of human bladder urothelium- express functional ASICs but no functional TRPV1 channels. In addition, we show that the levels of ASIC2 and ASIC3 mRNA are increased in the urothelium of patients suffering from BPS/IC. These data suggest that ASICs are involved in the pathology of BPS/IC.Finally, we demonstrate that APETx2 inhibits the sensory neuron specific voltage-dependent Na+ channel Nav1.8. APETx2 was previously shown to inhibit homo- or heterotrimeric ASIC3- containing channels with IC5o from 0.08 to 1 μΜ. We show that APETx2 also inhibits Nav1.8 with an ICsoof «2.6 μΜ. APETx2 reduces the maximal conductance and induces a depolarizing shift in the voltage dependence of activation of Nav1.8. In current-clamp experiments, APETx2 reduces the number of action potentials (APs) evoked by a current ramp. Nav1.8 mediates most of the current during the AP upstroke and has been shown to be an important mediator of inflammatory pain. The fact that APETx2 inhibits two ion channels involved in inflammatory pain suggests that APETx2 or derivatives may represent novel analgesic compounds.RésuméL'acidose tissulaire est observée durant l'inflammation et entraine la douleur chez l'humain. Des canaux ioniques activés par les protons (H+) sont fortement exprimés dans les neurones sensoriels du système nerveux périphérique. De ceux-ci, les Acid-Sensing Ion Channels [ASICs) et Transient Receptor Potential Vanilloid-1 (TRPV1) présentent une sensibilité adéquate à l'acidité pour servir de détecteurs d'acidose.Les ASICs sont membres de la famille Degenerin/Epithelial Na* Channel. Six sous-unités ASIC ont été identifiées chez les mammifères (ASICla, -lb, -2a, -2b, -3 et -4). Les ASICs forment des canaux sélectifs au Na\ insensibles au voltage et activés par les H+. Les canaux fonctionnels sont des homo- ou hétérotrimères de sous-unités ASIC. TRPV1 est un membre de la famille TRP de canaux ioniques. Les canaux TRPV1 sont activés par les H+, la chaleur (T>43°Ç), les lipides, la capsaicine, le voltage et d'autres stimulus. L'activation de TRPV1 entraine un courant soutenu non-sélectif. Un stimulus peut augmenter la réponse de TRPV1 à un autre stimulus. Les H+ peuvent, par exemple, induire un décalage vers des valeurs plus faibles de la courbe de dépendance à la concentration de TRPV1 pour la capsaicine. Il a été démontré que les ASICs et TRPV1 sont impliqués dans la douleur inflammatoire. En utilisant la technique du patch-clamp, nous avons étudié différents aspects de la fonction des ASICs et de TRPV1 dans des contextes associés à la douleur.Dans la première partie de cette thèse, nous caractérisons l'effet d'une augmentation de température de 25 à 35°C sur la fonction des canaux ASICs et TRPV1, dans des cellules CHO transfectées et dans des cultures primaires de neurones sensoriels (DRG) de rat. L'activation des ASICs entraine l'apparition d'un courant transitoire tandis que l'activation de TRPV1 entraine un courant soutenu. De plus, les ASICs et TRPV1 possèdent des dépendances au pH différentes. Nous évaluons la contribution relative des ASICs et de TRPV1 au signalement électrique induit par les H+ et nous concluons que les ASICs sont les senseurs d'acidité les plus importants dans les neurones sensoriels, dans le domaine de pH de 7.4 à 6.0, à température corporelle.Les ASICs et TRPV1 sont exprimés dans l'épithélium recouvrant l'intérieur de la vessie (l'urothélium). Le Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) est une condition médicale douloureuse associée à une dysfonction de la barrière urothéliale et à une inflammation. Dans la seconde partie de cette thèse, nous démontrons que des cellules urothéliales (de la lignée cellulaire TEU2) et des cellules provenant de cultures primaires d'épithéliums de vessies humaines expriment des canaux ASIC fonctionnels mais pas de TRPV1 fonctionnels. De plus, nous montrons que le niveau d'expression de ASIC2 et -3 est augmenté dans l'urothélium de la vessie de patients souffrant de BPS/IC. Ces données suggèrent que les ASICs sont impliqués dans la pathologie BPS/IC.Pour finir, nous démontrons que la toxine APETx2 inhibe le canal spécifique aux neurones sensoriels Nav1.8, un membre de la famille des canaux sodiques dépendants du potentiel. Il a été démontré précédemment que la toxine APETx2 inhibe les canaux contenant une ou plusieurs sous-unités ASIC3 avec un ICso entre 0.08 et 1 μΜ. Nous montrons que la toxine APETx2 inhibe Nav1.8 avec un IC50 de «2.6 μΜ. La toxine APETx2 réduit la conductance maximale et induit un décalage de la dépendance au potentiel de Nav1.8 vers des valeurs plus positives. Dans des expériences de courant imposé sur des neurones sensoriels, la toxine APETx2 réduit le nombre de potentiels d'action induits par une rampe de courant. Nav1.8 est responsable de la majeure partie du courant durant la phase ascendante du potentiel d'action et a été démontré comme étant un médiateur important de la douleur inflammatoire. L'inhibition de deux types de canaux, impliqués dans la douleurs inflammatoire, par la toxine APETx2, suggère que cette dernière ou ses dérivés représentent des composés analgésiques prometteurs.

Fonaments i actuacions de lideratge sistèmic d'un equip de bàsquet professional i futures aplicacions

El treball de recerca “Fonaments i actuacions de lideratge sistèmic d’un equip de bàsquet professional i futures aplicacions” fa l’anàlisi d’una experiència real vinculada al món de l’esport professional. Es pretén donar a conèixer com l’estructuració del coneixement de l’entrenador pot afavorir el bon funcionament de l’equip. L’estructuració ens genera criteri i coherència a l’hora de prendre decisions.Es reconeix a l’entrenador com una persona treballadora, apassionada per la seva feina i en constant creixement individual. Valors com la humilitat, l’entusiasme, el compromís, la generositat i l’autoexigència es converteixen en adjectius fonamentals del nostre entrenador.L’estudi en l’autoconeixement en conceptes com lideratge, nivells neurològics, talent i motivació esdevenen el pal de paller en la construcció de l’equip. Un equip amb identitat pròpia, on el benefici pel bé comú (equip) està per sobre de tot, cooperatiu, compromès, i on la figura de l’entrenador intuïtiu amb coneixement influeix més per convenciment que per autoritat.El treball del dia a dia de l’entrenador i de l´equip es fonamenta en l’organització dels pilars de l’entrenador: flexibilitat, creixement de l’entrenador, equip, marges col·lectiu i individual són els motors del bon funcionament del col·lectiu. En el treball presentat, es destaca la importància de saber diferenciar, en el rendiment d’un equip, dues vessants: una més objectiva (tècnica, tàctica, estratègia i física) i l’altra on el factor humà és determinant. La investigació aprofundeix en aquest segon factor i el reconeix com a preferent. Per acabar es presenten tot un seguit d’actuacions utilitzades al llarg de la investigació amb la finalitat de generar, mantenir i millorar l’equip al mateix temps que es mostren diferents eines per tal d’optimitzar l’eficiència de les actuacions. La investigació pretén ser una experiència útil i enriquidora a l’hora d’estructurar el coneixement per tal de poder ser utilitzat en futures aplicacions.

Like milk or wine: Does firm performance improve with age?

Our empirical literature review shows that little is known about how firm performance changes with age, presumably because of the paucity of data on firm age. For Spanish manufacturing firms, we analyse the firm performance related to firm age between 1998 and 2006. We find evidence that firms improve with age, because ageing firms are observed to have steadily increasing levels of productivity, higher profits, larger size, lower debt ratios, and higher equity ratios. Furthermore, older firms are better able to convert sales growth into subsequent growth of profits and productivity. On the other hand, we also found evidence that firm performance deteriorates with age. Older firms have lower expected growth rates of sales, profits and productivity, they have lower profitability levels (when other variables such as size are controlled for), and also that they appear to be less capable to convert employment growth into growth of sales, profits and productivity. Keywords: firm age, firm growth, LAD, financial structure, vector autoregression JEL CODES: L25, L20

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Figures d'un ancêtre

Parmi les personnages de la Bible hébraïque, Abraham occupe une place privilégiée. Avec Moïse il est en quelque sorte le fondateur du judaïsme. Contrairement à Moïse, Abraham est devenu l'ancêtre commun des trois religions monothéistes : judaïsme, christianisme, islam. Ce patriarche semble jouir d'un incontestable pouvoir d'intégration, puisque des courants théologiques différents peuvent se reconnaître en lui. Il existe donc plusieurs lectures possibles de la figure de cet ancêtre. Le fondement de toutes ces lectures, à savoir le cycle d'Abraham, qui se trouve dans le livre de la Genèse (Gn 11,27-25,18), contient lui-même déjà une diversité de vues et de représentations du patriarche.

Innovation and absorptive capacity: What is the role of technological frontier?

This paper explores how absorptive capacity affects the innovative performance and productivity dynamics of Spanish firms. A firm’s efficiency levels are measured using two variables: the labour productivity and the Total Factor Productivity (TFP). The theoretical framework is based on the seminal contributions of Cohen and Levinthal (1989, 1990) regarding absorptive capacity; and the applied framework is based on the four-stage structural model proposed by Crépon, Duguet and Mairesse (1998) for setting the determinants of R&D, the effects of R&D activities on innovation outputs, and the impacts of innovation on firm productivity. The present study uses a twostage structural model. In the first stage, a probit estimation is used to investigate how the sources of R&D, the absorptive capacity and a vector of the firm’s individual features influence the firm’s likelihood of developing innovations in products or processes. In the second phase, a quantile regression is used to analyze the effect of R&D sources, absorptive capacity and firm characteristics on productivity. This method shows the elasticity of each exogenous variable on productivity according to the firms’ levels of efficiency, and thus allows us to distinguish between firms that are close to the technological frontier and those that are further away from it. We used extensive firm-level panel data from 5,575 firms for the 2004-2009 period. The results show that the internal absorptive capacity has a strong impact on the productivity of firms, whereas the role of external absorptive capacity differs according to nature of the each industry and according the distance of firms from the technological frontier. Key words: R&D sources, innovation strategies, absorptive capacity, technological distance, quantile regression.

Factores Asociados a Deficiencia de Vitamina D y a Niveles Elevados de PTH en Pacientes con Infección VIH Atendidos en Barcelona

Estudi transversal de pacients VIH en els que es va determinar colecalciferol (25-OH- Vit.D3) i PTH, excloint a pacients amb insuficiència renal, hepàtica i nivells plasmàtics anormals de calci i/o fósfor Es van incloure 566 pacients, amb una exposició a tenofovir del 56,4%. La prevalència de vitamina D insuficient va der del 71,2% i la deficiència del 39,6% . La PTH es va determinar en 228 casos, presentant nivells elevats 86 d’ells (37,7%). Els factors de risc ajustats de deficiència de vitamina D van ser, ésser de raza no blanca i la morbilitat psiquiàtrica, essent la lipoatròfia, un factor protector. Els factors de risc independents de nivells elevats de PTH van ser: Vitamina D&12 ng/ml: OR: 2,14 (IC95%: 1,19-3,82, p: 0,01) i l’ exposició a tenofovir: OR: 3,55 (IC95%: 1,62-7,7, p: 0,002).