75 research outputs found

    An Overview of the Obese-Asthma Phenotype in Children

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    Asthma is the most common chronic disease in childhood. Overweight and obesity are included among the comorbidities considered in patients with difficult-to-treat asthma, suggesting a specific phenotype of the disease. Therefore, the constant increase in obesity prevalence in children and adolescents raises concerns about the parallel increase of obesity-associated asthma. The possible correlation between obesity and asthma has been investigated over the last decade by different authors, who suggest a complex multifactorial relationship. Although the particular non-eosinophilic endotype of obesity-related asthma supports the concept that high body weight precedes asthma development, there is ongoing debate about the direct causality of these two entities. A number of mechanisms may be involved in asthma in combination with obesity disease in children, including reduced physical activity, abnormal ventilation, chronic systemic inflammation, hormonal influences, genetics and additional comorbidities, such as gastroesophageal reflux and dysfunctional breathing. The identification of the obesity-related asthma phenotype is crucial to initiate specific therapeutic management. Besides the cornerstones of asthma treatment, lifestyle should be optimized, with interventions aiming to promote physical exercise, healthy diet, and comorbidities. Future studies should clarify the exact association between asthma and obesity and the mechanisms underlying the pathogenesis of these two related conditions with the aim to define personalized therapeutic strategies for asthma management in this population

    Vaccines in children with inflammatory bowel disease: Brief review

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    Incidence of inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. Children with IBDs have a dysfunctional immune system and they are frequently treated with immunomodulating drugs and biological therapy, which significantly impair immune system functions and lead to an increased risk of infections. Vaccines are essential to prevent at least part of these infections and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended. However, several factors might lead to insufficient immunization. In this paper, present knowledge on the use of vaccines in children with IBDs is discussed. Literature review showed that despite a lack of detailed quantification of the risk of infections in children with IBDs, these children might have infections more frequently than age-matched healthy subjects, and at least in some cases, these infections might be even more severe. Fortunately, most of these infections could be prevented when recommended schedules of immunization are carefully followed. Vaccines given to children with IBDs generally have adequate immunogenicity and safety. Attention must be paid to live attenuated vaccines that can be administered only to children without or with mild immune system function impairment. Vaccination of their caregivers is also recommended. Unfortunately, compliance to these recommendations is generally low and multidisciplinary educational programs to improve vaccination coverage must be planned, in order to protect children with IBD from vaccine-preventable diseases

    Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis

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    Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SSc(Fib+)) with that obtained from six SSc patients without pulmonary fibrosis (SSc(Fib-)) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SSc(Fib+ )patients and SSc(Fib- )patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SSc(Fib+ )patients compared with SSc(Fib- )patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SSc(Fib+ )patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease

    Kinin B(1) receptor deficiency leads to leptin hypersensitivity and resistance to obesity

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    OBJECTIVE-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.RESEARCH DESIGN and METHODS-Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity.RESULTS-Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.CONCLUSIONS-Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.Universidade Federal de SĂŁo Paulo, Dept Biophys, BR-04023062 SĂŁo Paulo, BrazilUniv Mogi das Cruzes, Mogi Das Cruzes, BrazilUniversidade Federal de SĂŁo Paulo, Dept Physiol, BR-04023062 SĂŁo Paulo, BrazilSanofi Aventis, Montpellier, FranceUniversidade Federal de SĂŁo Paulo, Dept Med, BR-04023062 SĂŁo Paulo, BrazilInst Natl Sante & Rech Med, Dept Renal & Cardiac Remodeling, U858 I2MR, Toulouse, FranceUniv Toulouse 3, Inst Med Mol Rangueil, F-31062 Toulouse, FranceInst Natl Rech Agron AgroParisTech, UMR914 Nutr Physiol & Ingest Behav, Paris, FranceMax Delbruck Ctr Mol Med, Berlin, GermanyUniversidade Federal de SĂŁo Paulo, Dept Biophys, BR-04023062 SĂŁo Paulo, BrazilUniversidade Federal de SĂŁo Paulo, Dept Physiol, BR-04023062 SĂŁo Paulo, BrazilUniversidade Federal de SĂŁo Paulo, Dept Med, BR-04023062 SĂŁo Paulo, BrazilWeb of Scienc

    Characterization of HV-CMOS detectors in BCD8 technology and of a controlled hybridization technique

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    Radiation detectors built in high-voltage and high-resistivity CMOS technology are an interesting option for the large area pixel-trackers sought for the upgrade of the Large Hadron Collider experiments. A characterisation of the BCD8 technology by STMicroelectronics process has been performed to evaluate its suitability for the realisation of CMOS sensors with a depleted region of several tens of micrometer. Sensors featuring 50 7250 \u3bcm2 pixels on a 125 \u3a9cm resistivity substrate have been characterized. The response to ionizing radiation is tested using radioactive sources and an X-ray tune, reading out the detector with an external spectroscopy chain. Irradiation tests were performed up to proton fluences exceeding 5 c51015 p/cm2 and they show the depletion and breakdown voltages increases with irradiation. A hybridization process for capacitive coupling has been developed. Assemblies have been performed using the ATLAS FE-I4 readout ASIC and prototype CMOS sensors. Measurements show a planarity better than 1.5 \u3bcm peak-to-peak on the 5 mm length of the HV-CMOS chip. To evaluate more precisely the achievable uniformity dummy chips of FE-I4 sizes have been made on 6-inch wafers. The measurement of the 24 capacitors on each chip is expected to achieve a precise estimation of the real thickness uniformity. The goal is to achieve less then 10% variation on the glue thickness ( 3c0.5 \u3bcm)

    Polyamide-Scorpion Cyclam Lexitropsins Selectively Bind AT-Rich DNA Independently of the Nature of the Coordinated Metal

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    Cyclam was attached to 1-, 2- and 3-pyrrole lexitropsins for the first time through a synthetically facile copper-catalyzed “click” reaction. The corresponding copper and zinc complexes were synthesized and characterized. The ligand and its complexes bound AT-rich DNA selectively over GC-rich DNA, and the thermodynamic profile of the binding was evaluated by isothermal titration calorimetry. The metal, encapsulated in a scorpion azamacrocyclic complex, did not affect the binding, which was dominated by the organic tail

    Contribution to the knowledge of lichen flora of inland sand dunes in the western Po Plain (N Italy)

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    This paper describes the lichen flora surveyed in inland sand dunes, called dossi, in the western Po Plain (Lombardy region, Italy). Here, lichens were marginally known in comparison with the epigaeous component, but they were never studied before in relation to the epiphytic, epixylic and epilithic components. The floristic list includes 50 species; ecological and chorological analyses were carried out. Thirteen lichen species observed on various substrata were not reported in the lichen list of the Ticino Natural Park, which distances only few kilometres from our study area. Nine species are new for the Po phytoclimatic region and one species, Cladonia portentosa, is new for Lombardy. Particularly interesting are some species related to the Corynephorus grasslands, such as Cladonia sp. pl. and Stereocauloncondensatum, and three species usually absent, at our latitudes, beneath the montane belt: Cladonia digitata, Hypocenomyce scalaris and Parmeliopsis ambigua. These data confirm the importance of inland sand dunes for lichen diversity of the Po Plain. Some preliminary remarks concerning the management of the habitats hosting lichens are given, with particular emphasis to their conservation. Suggested actions include the possibility to keep woody coarse debris, to favour epixylic species, and mechanical disturbance, dispersal of lichen fragments and sheep grazing, to favour epigaeous species

    AgentService in a hand

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    In this paper we present AgentService Mobile: an infrastructure aimed to the execution of agents on devices with limited resources. The mobile device plays the role of a client which consumes a set of services exposed by the AgentService platform. This is the entry of AgentService in a SOA context, with the main goal to open the multi-agent platform to the outside, by using the most recent service oriented technologies
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