177,145 research outputs found
Bronchodilator effects of exercise hyperpnea and albuterol in mild-to-moderate asthma
No full textJ Appl Physiol. 2009 Aug;107(2):494-9. Epub 2009 Jun 18.
Bronchodilator effects of exercise hyperpnea and albuterol in mild-to-moderate asthma.
Milanese M, Saporiti R, Bartolini S, Pellegrino R, Baroffio M, Brusasco V, Crimi E.
Source
S.C. Pneumologia, Ospedale S. Corona, Pietra Ligure, Italy.
Abstract
In asthmatic patients, either bronchodilatation or bronchoconstriction may develop during exercise. In 18 patients with mild-to-moderate asthma, we conducted two studies with the aims to 1) quantify the bronchodilator effect of hyperpnea induced by incremental-load maximum exercise compared with effects of inhaled albuterol (study 1, n=10) and 2) determine the time course of changes in airway caliber during prolonged constant-load exercise (study 2, n=8). In both studies, it was also investigated whether the bronchodilator effects of exercise hyperpnea and albuterol are additive. Changes in airway caliber were measured by changes in partial forced expiratory flow. In study 1, incremental-load exercise was associated with a bronchodilatation that was approximately 60% of the maximal bronchodilatation obtainable with 1,500 microg of albuterol. In study 2, constant-load exercise was associated with an initial moderate bronchodilatation and a late airway renarrowing. In both studies, premedication with inhaled albuterol (400 microg) promoted sustained bronchodilatation during exercise, which was additive to that caused by exercise hyperpnea. In conclusion, in mild-to-moderate asthmatic individuals, hyperpnea at peak exercise was associated with a potent yet not complete bronchodilatation. During constant-load exercise, a transient bronchodilatation was followed by airway renarrowing, suggesting prevalence of constrictor over dilator effects of hyperpnea. Finally, the bronchodilator effect of hyperpnea was additive to that of albuterol.
PMID: 19541736 [PubMed - indexed for MEDLINE
Desarrollo de herramientas para enfrentar la resistencia de la garrapata Rhipicephalus microplus
No full textLa parasitosis por la garrapata Rhipicephalus microplus (R. microplus) puede representar una limitante para la producción bovina desde el punto de vista sanitario, así como económico. Por lo tanto, es muy importante su control, el cual se ha visto desafiado por la selección hacia la resistencia a los diferentes principios activos habilitados en Uruguay al punto de diagnosticarse poblaciones multirresistentes. Para sortear esta dificultad es que existen diferentes bioensayos que se utilizan de rutina y permiten determinar el perfil de resistencia de una población de R. microplus, lo que brinda una orientación más precisa para su tratamiento. Sin embargo, estos llevan aproximadamente 60 días en brindar resultados. La resonancia magnética nuclear es una técnica que nos permite elucidar las moléculas de una muestra, como pueden ser los metabolitos. De esta manera, mediante un estudio metabolómico, se podrían identificar diferencias entre muestras de garrapatas resistentes y susceptibles a los diferentes grupos químicos garrapaticidas. Disponer de esta herramienta para el diagnóstico de resistencia podría acortar los tiempos de obtención de resultados. Además de abordar el diagnóstico es necesario contar con nuevas entidades químicas para el tratamiento garrapaticida. Para ello el estudio de moléculas en proteínas blanco es un camino a seguir. En este sentido las enzimas Triosa fosfato isomerasa y la Glutatión S transferasa son importantes en el metabolismo de la garrapata. Por lo tanto, identificar moléculas que presenten actividad inhibitoria de estas, resulta en un importante primer paso en la búsqueda y detección de moléculas con poder garrapaticida. En este trabajo se logró desarrollar un método de diagnóstico que diferencia garrapatas susceptibles de resistentes en 7 días, además se identificaron moléculas con inhibición selectiva de enzimas esenciales de la garrapata que demostraron actividad garrapaticida en larvas y adultas.Parasitosis caused by Rhipicephalus microplus (R. microplus) tick can signify a limitation for bovine production systems from a health and economic point of view. However, its control, which turns out to be a very important issue, has been challenged by the emergence of resistance to the different active ingredients registered in Uruguay. So much so that currently multi-resistant populations have been diagnosticated. In order to get around this problem different bioassays exist that are routinely used and allow us to determine the resistance profiles of a R. microplus population, giving a more precise orientation for its treatment. However, these results take approximately 60 days in giving the results. Nuclear magnetic resonance is a technique that allows the elucidation of molecules of a sample, such as metabolites. This way, differences between samples of susceptible and resistant ticks, to the different active ingredients, could be identified. Having this tool could shorten times for obtaining results once the sample has been received. Besides addressing the diagnosis problem, it is also necessary to count on new chemical entities for the tickicide treatments. Therefore, the study of molecules on the activity of blank proteins is one way to pursue. Thus Triosephosphate-isomerase and Glutathione S tranferase are two important enzymes on ticks´ metabolism. To identify molecules which present an inhibitory activity of these enzymes results on an important first step on the search and detection of molecules with a tickicide effect. This study managed to develop a diagnostic method that allows to differentiate susceptible from resistant tick populations on 7 days. Besides it has identified molecules with selective enzyme inhibition, on enzymes which are essential for ticks, as well as showing tickicide activity on adult and larvae ticks
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
On the existence of Nash equilibrium in electoral competition
No full textThis paper generalizes previous existence results on unidimensional electoral competition, by extending the traditional two-party electoral game to the case where parties have mixed motivations, in the sense that they are interested in winning the election, but also in the policy implemented after the contest. Although this game has discontinuous payoffs, it satisfies payoff security and reciprocally upper semi- continuity. However, conditional payoffs might violate quasi-concavity. Hence, our first result shows that the existence of a pure-strategy Nash equilibrium can be guaranteed only if parties' interests are symmetric. Instead, we prove that the mixed extension satisfies better reply security and, therefore, that a mixed-strategy equilibrium always exists. We also characterize the set of equilibria for a tractable version of the model. This shows that the interaction between the electoral uncertainty, the aggregate level of opportunism and its distribution among parties shape the equilibrium strategies. In particular, when the opportunism is large and asymmetrically distributed, the support of each mixed-strategy equilibrium is a closed interval located on one side of the median. Further, as the uncertainty increases, the probability distributions concentrate on the extremes of the support. And the mixed-strategy equilibrium vanishes above a critical level, over which each party plays a pure strategy in its own ideological side.Electoral competition, mixed motivations, discontinuous games, Nash equilibrium.
Volumetric spine BMD impairement in diabetic children and adolescents is not related to change in calcium homeostasis
No full textAutimmune thyroiditis (AT) in T1DM: role of TPO and TG Ab as predictor of thyroid failure
No full textIn silico identification of small molecules engaging the TNFR2-TNF-α interaction: a novel approach for targeting demyelinating diseases
No full textTumor necrosis factor alpha (TNF-α) is a cytokine secreted by macrophages, involved in immune and proinflammatory responses, cellular proliferation and differentiation. TNF-α exists in two isoforms: a soluble one, that participates to pathological mechanisms of demyelinating and neurodegenerative diseases preferably via TNF receptor 1 (TNFR1), and a transmembrane form, which can mediate neurorepair and remyelination via TNFR2.
Due to the protective role of TNFR2 in central nervous system (CNS), our aim was to identify ligands able to selectively enhance TNFR2::TNF-α engagement for promoting its reparative effects.
First, we characterized in silico the differences between TNFR1 and TNFR2 structures. We found that the interaction surfaces of both receptors show opposite electrostatic potential surfaces, suggesting that the selective engagement of the two TNF-α isoforms to TNFR1 or TNFR2 may depend on these electrostatic differences. Then, we tested a large library of commercially available drug-like compounds against the TNFR2::TNF-α complex, through virtual high-throughput screening. We identified 20 compounds with high affinity for the complex. Moreover, each TNFR2::TNF-α complex in association with the investigated ligands showed a G binding free energy gain with respect to the complex alone, suggesting that all the 20 compounds may enhance the affinity of TNF-α for TNFR2.
Finally, to assess if these compounds could be efficiently delivered to the brain, their ability to target CNS was predicted in silico by computing significant pharmacokinetic descriptors. Five out of the 20 selected compounds were characterized by a potential CNS activity.
To date, all the available approaches targeting the TNFR1/2: TNF-α axis for promoting TNFR2 neuroprotection are based on biotechnological drugs. On this basis, our data pave the way for the development of a new therapeutic strategy for demyelinating diseases based on TNFR2 engagement by small molecules with drug-like properties
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