Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions

Cell motility is an essential process that depends on a coherent, cross-linked actin cytoskeleton that physically coordinates the actions of numerous structural and signaling molecules. The actin cross-linking protein, filamin (Fln), has been implicated in the support of three-dimensional cortical actin networks capable of both maintaining cellular integrity and withstanding large forces. Although numerous studies have examined cells lacking one of the multiple Fln isoforms, compensatory mechanisms can mask novel phenotypes only observable by further Fln depletion. Indeed, shRNA-mediated knockdown of FlnA in FlnB¿/¿ mouse embryonic fibroblasts (MEFs) causes a novel endoplasmic spreading deficiency as detected by endoplasmic reticulum markers. Microtubule (MT) extension rates are also decreased but not by peripheral actin flow, because this is also decreased in the Fln-depleted system. Additionally, Fln-depleted MEFs exhibit decreased adhesion stability that appears in increased ruffling of the cell edge, reduced adhesion size, transient traction forces, and decreased stress fibers. FlnA¿/¿ MEFs, but not FlnB¿/¿ MEFs, also show a moderate defect in endoplasm spreading, characterized by initial extension followed by abrupt retractions and stress fiber fracture. FlnA localizes to actin linkages surrounding the endoplasm, adhesions, and stress fibers. Thus we suggest that Flns have a major role in the maintenance of actin-based mechanical linkages that enable endoplasmic spreading and MT extension as well as sustained traction forces and mature focal adhesions.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Telemedicine Experience for Chronic Care in COPD

Information and telecommunication technologies are called to play a major role in the changes that healthcare systems have to face to cope with chronic disease. This paper reports a telemedicine experience for the home care of chronic patients suffering from chronic obstructive pulmonary disease (COPD) and an integrated system designed to carry out this experience. To determine the impact on health, the chronic care telemedicine system was used during one year (2002) with 157 COPD patients in a clinical experiment; endpoints were readmissions and mortality. Patients in the intervention group were followed up at their homes and could contact the care team at any time through the call center. The care team shared a unique electronic chronic patient record (ECPR) accessible through the web-based patient management module or the home visit units. Results suggest that integrated home telemedicine services can support health professionals caring for patients with chronic disease, and improve their health.We have found that simple telemedicine services (ubiquitous access to ECPR, ECPR shared by care team, accessibility to case manager, problem reporting integrated in ECPR) can increase the number of patients that were not readmitted (51% intervention, 33% control), are acceptable to professionals, and involve low installation and exploitation costs. Further research is needed to determine the role of telemonitoring and televisit services for this kind of patients.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.

Les competències genèriques en l’educació superior. Recerca sobre la percepció dels estudiants respecte l’impacte que té la metodologia de Seminari de Blanquerna en l’adquisició de competències genèriques.

L'objectiu de l'article és contribuir a la reflexió actual sobre les competències genèriques en l'educació superior. Es va desenvolupar una investigació sobre l'adquisició de competències genèriques en els programes de ciències socials de llicenciatura (Psicologia) de Blanquerna-Universitat Ramon Llull. Per a aquests estudis s’ha estat desenvolupant una metodologia innovadora anomenada Seminari. El seu propòsit se centra, entre altres qüestions, en el desenvolupament de competències genèriques. En primer lloc, les competències genèriques són avaluades respecte si són o no són percebudes com a importants per part dels estudiants d'últim curs, i respecte quin és el context principal per la seva adquisició. La metodologia de Seminari, que es caracteritza en aquest estudi, correlaciona més estretament amb la percepció de la importància de les competències en el món professional que els altres contextos, fins i tot les assignatures o l’adquisició de competències fora de la universitat. La investigació té com a objectiu el contribuir a aconseguir una millor comprensió dels millors contextos per a l'adquisició de competències genèriques en l'educació superior i de la importància d’aquestes en el món professional. Es desenvolupa implícitament una metodologia per a l'estudi de l'adquisició de competències i per a la caracterització d'un model educatiu centrat en competències.

Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Microvariation in the languages of the Iberian Peninsula

This issue of the Catalan Journal of Linguistics was conceived with the idea to promote comparative studies of the languages spoken in the Iberian Peninsula. The importance of comparison in linguistics dates back to neogrammarians in the xix century due to their interest of discovering the common roots of most of the languages spoken in Europe. In order to get to that objective, comparison of phonological patterns were crucial to retrieve the common Indo-European origins

La viabilidad económica de una Cataluña independiente

El objetivo del presente artículo es demostrar la viabilidad económica de Cataluña como Estado independiente, analizando en particular los aspectos comerciales y hacendísticos. Los datos demuestran que Cataluña tiene un nivel de PIB per cápita por encima de la media UE-15, y a pesar de ser un país de pequeña dimensión cuenta con una economía muy abierta que le permite obtener efectos de escala en el crecimiento y ser un país competitivo. Asimismo, en términos hacendísticos, se estima que una Cataluña independiente tendría una ganancia fiscal de alrededor del 7% del PIB, lo que le permitiría no sólo mantener el actual Estado del Bienestar sino incluso incrementarlo.

Integració docència i investigació: automedicació i ús de teràpies complementàries en estudiants universitaris

Integrar docencia e investigación en el ámbito del consumo de fármacos y el uso de terapias complementarias por los estudiantes universitarios de Enfermería y de Administración y Dirección de Empresas (ADE) frente a los trastornos de salud. El objetivo docente es fomentar la competencia transversal “Capacidad de aprendizaje y Responsabilidad” relacionada con la integración los conocimientos necesarios para poder cuidarse y prevenir riesgos. Los resultados del estudio se comunicarán a través del Campus Virtual a los alumnos de las dos facultades (asignaturas a concretar por los profesores de los dos centros) e irán acompañados de un feed-back con recomendaciones sobre el uso responsable de fármacos y terapias complementarias.

Integració docència i investigació: automedicació i ús de teràpies complementàries en estudiants universitaris

Integrar docencia e investigación en el ámbito del consumo de fármacos y el uso de terapias complementarias por los estudiantes universitarios de Enfermería y de Administración y Dirección de Empresas (ADE) frente a los trastornos de salud. El objetivo docente es fomentar la competencia transversal “Capacidad de aprendizaje y Responsabilidad” relacionada con la integración los conocimientos necesarios para poder cuidarse y prevenir riesgos. Los resultados del estudio se comunicarán a través del Campus Virtual a los alumnos de las dos facultades (asignaturas a concretar por los profesores de los dos centros) e irán acompañados de un feed-back con recomendaciones sobre el uso responsable de fármacos y terapias complementarias.

Grup d'Innovació Docent en Farmacologia (GIDOF)

Podeu consultar la Setena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/43352

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'

Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogeneic enzymes by modifying nutrient sensing factors in rats

High consumption of fructose-sweetened beverages has been linked to a high prevalence of chronic metabolic diseases. We have previously shown that a short course of fructose supplementation as a liquid solution induces glucose intolerance in female rats. In the present work, we characterized the fructose-driven changes in the liver and the molecular pathways involved. To this end, female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14 days. Glucose and pyruvate tolerance tests were performed, and the expression of genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways was evaluated. Fructose-supplemented rats showed increased plasma glucose excursions in glucose and pyruvate tolerance tests and reduced hepatic expression of several genes related to insulin signaling, including insulin receptor substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to an increase in its acetylation state driven by a reduced expression and activity of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose consumption elevated liver expression of the spliced form of X-box-binding-protein-1 as a consequence of an increase in the activity of the mammalian target of rapamycin 1 and protein 38-mitogen activated protein kinase (p38-MAPK). Liquid fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling without increasing the expression of key gluconeogenic enzymes.

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