0000000000003302

AUTHOR

Alfredo De Diego

0000-0002-8371-0141

showing 8 related works from this author

Role of tetrahydrobiopterin in pulmonary vascular remodelling associated with pulmonary fibrosis

2013

[Background]: Pulmonary hypertension in idiopathic pulmonary fibrosis (IPF) is indicative of a poor prognosis. Recent evidence suggests that tetrahydrobiopterin (BH4), the cofactor of nitric oxide synthase (NOS), is involved in pulmonary hypertension and that pulmonary artery endothelial-to-mesenchymal transition (EnMT) may contribute to pulmonary fibrosis. However, the role of BH4 in pulmonary remodelling secondary to pulmonary fibrosis is unknown. This study examined the BH4 system in plasma and pulmonary arteries from patients with IPF as well as the antiremodelling and antifibrotic effects of the BH4 precursor sepiapterin in rat bleomycin-induced pulmonary fibrosis and in vitro EnMT mod…

MalePulmonary and Respiratory Medicinemedicine.medical_specialtySepiapterinPathologyNitric Oxide Synthase Type IIIHypertension PulmonaryPulmonary FibrosisNitric Oxide Synthase Type IIEnzyme-Linked Immunosorbent AssayPulmonary ArteryReal-Time Polymerase Chain ReactionEndothelial NOSchemistry.chemical_compoundIdiopathic pulmonary fibrosisInternal medicinemedicine.arteryPulmonary fibrosismedicineAnimalsHumansRats WistarGTP CyclohydrolaseSepiapterin reductaseChromatography High Pressure LiquidAgedbusiness.industryNitrotyrosineMiddle Agedmedicine.diseaseBiopterinImmunohistochemistryPulmonary hypertensionRatsAlcohol OxidoreductasesDisease Models AnimalEndocrinologychemistryPulmonary arteryTyrosineFemaleEndothelium Vascularbusiness
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Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

2016

Background: Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD patients were used to compare the anti-inflammatory effects of aclidinium bromide (a long-acting muscarinic antagonist) with corticosteroids and their potential additive effect. Methods: Human sputum and blood neutrophils were isolated from healthy individuals ( n = 37), patients with stable COPD ( n = 52) and th…

Male0301 basic medicineNeutrophilsVesicular Acetylcholine Transport ProteinsAnti-Inflammatory AgentsDrug ResistanceNon-neuronal cholinergic systemPulmonary Disease Chronic Obstructive0302 clinical medicineMuscarinic acetylcholine receptorCOPDDrug SynergismAclidinium bromideMuscarinic acetylcholine receptor M2Middle AgedReceptors MuscarinicBronchodilator AgentsCorticosteroidDrug Therapy CombinationFemaleInflammation Mediatorsmedicine.drugPulmonary and Respiratory Medicinemedicine.medical_specialtyCombination therapymedicine.drug_classCorticosteroid resistanceMuscarinic AntagonistsFluticasone propionateCholine O-Acetyltransferase03 medical and health sciencesAclidinium bromideInternal medicinemedicineHumansCOPDAgedDose-Response Relationship Drugbusiness.industryResearchSputumMuscarinic antagonistmedicine.disease030104 developmental biologyEndocrinology030228 respiratory systemCase-Control StudiesFluticasonebusinessTropanesRespiratory Research
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In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /β2-adrenoceptor agonist (MABA) comp…

2019

Recent evidence indicates that AZD8999 (LAS190792), a novel muscarinic acetylcholine receptor antagonist and β2-adrenoceptor agonist (MABA) in development for chronic respiratory diseases, induces potent and sustained relaxant effects in human bronchi by adressing both muscarinic acetylcholine receptors and β2-adrenoceptor. However, the anti-inflammatory effects of the AZD8999 monotherapy or in combination with corticosteroids are unknown. This study investigates the anti-inflammatory effects of AZD8999 in monotherapy and combined with fluticasone propionate in neutrophils from healthy and chronic obstructive pulmonary disease (COPD) patients. Peripheral blood neutrophils from healthy and C…

MalePulmonologyNeutrophilsPhysiologyAnti-Inflammatory AgentsPharmacologyPathology and Laboratory MedicineBiochemistryPulmonary Disease Chronic ObstructiveWhite Blood CellsGlucocorticoid receptorAnimal CellsMuscarinic acetylcholine receptorMedicine and Health SciencesPost-Translational ModificationPhosphorylationReceptorImmune ResponseMultidisciplinaryPharmaceuticsQRDrug SynergismMiddle AgedReceptors MuscarinicHealthy VolunteersBody FluidsChemistryBloodPhysical SciencesQuinolinesMedicineDrug Therapy CombinationFemalemedicine.symptomCellular TypesAnatomymedicine.drugResearch ArticleSignal TransductionAgonistTransmembrane Receptorsmedicine.drug_classp38 mitogen-activated protein kinasesChronic Obstructive Pulmonary DiseaseImmune CellsScienceImmunologyInflammationMuscarinic AntagonistsThiophenesFluticasone propionateSigns and SymptomsDrug TherapyCyclohexanesDiagnostic MedicinemedicineHumansAdrenergic beta-2 Receptor AgonistsAgedInflammationBlood CellsDose-Response Relationship Drugbusiness.industryAntagonistChemical CompoundsBiology and Life SciencesProteinsCell BiologyAcetylcholine ReceptorsFluticasoneMuscarinic Acetylcholine ReceptorsReceptors Adrenergic beta-2PropionatesbusinessReceptor Antagonist TherapyPLoS ONE
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Determinants of Dyspnea in Patients with Different Grades of Stable Asthma

2003

Dyspnea is a main feature of symptomatology in asthma, and its perception does not necessarily correlates well with airway obstruction. The aim of this study was twofold: (1) to identify factors determining the subjective degree of dyspnea in patients with different grades of stable bronchial asthma and (2) to compare various clinical methods existing for grading dyspnea. The investigation comprised 153 outpatients with stable asthma. The parameters studied were the following: demographic characteristic of subjects, baseline dyspnea score by means of three clinical instruments (baseline dyspnea index [BDI], Medical Research Council [MRC] scale, and modified Borg scale), asthma severity, sta…

AdultLung DiseasesMalePulmonary and Respiratory Medicinemedicine.medical_specialtyActivities of daily livingAdolescentSeverity of Illness IndexQuality of lifeHumansImmunology and AllergyMedicineDepression (differential diagnoses)AgedAsthmabusiness.industryMental DisordersRespiratory diseaseAge FactorsBaseline Dyspnea IndexMiddle AgedAirway obstructionmedicine.diseaseAsthmarespiratory tract diseasesDyspneaPediatrics Perinatology and Child HealthPhysical therapyAnxietyFemalemedicine.symptombusinessJournal of Asthma
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Mucin 1 deficiency mediates corticosteroid insensitivity in asthma

2019

BACKGROUND: The loss of corticosteroid efficacy is an important issue in severe asthma management and may lead to poor asthma control and deterioration of airflow. Recent data indicate that Mucin 1 (MUC1) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis, but the role of MUC1 in uncontrolled severe asthma is unknown. The objective was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in asthma. METHODS: Mucin 1 expression was evaluated by real-time PCR in human bronchial epithelial cells (HBEC) and blood neutrophils from uncontrolled severe asthma (n=27), controlled mild asthma (n=16), and healthy subjects (n=13). IL-8, MMP9, and GM-CSF …

severe asthma0301 basic medicineLipopolysaccharideNeutrophilsmedicine.drug_classcorticosteroid insensitivityImmunologyAnti-Inflammatory AgentsDrug ResistanceMUC1DexamethasoneMice03 medical and health scienceschemistry.chemical_compoundReceptors Glucocorticoid0302 clinical medicineGlucocorticoid receptorAdrenal Cortex Hormonesimmune system diseasesmedicineAnimalsHumansImmunology and AllergyCells CulturedMUC1DexamethasoneAsthmabiologybusiness.industryMucin-1MucinEpithelial Cellsmedicine.diseaseAsthmarespiratory tract diseasesOvalbumin030104 developmental biology030228 respiratory systemchemistryCase-Control StudiesImmunologybiology.proteinCorticosteroidbusinessmedicine.drugAllergy
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Gender Differences in Health‐Related Quality of Life Among Patients with Asthma

2004

This study has a twofold objective: 1) to explore to what extent suffering from asthma affects the HRQL of men and women differently at several stages of disease severity and 2) to analyze whether the informed poorer HRQL of asthmatic women is related to their higher scores on instruments measuring emotionally disordered symptoms. One hundred fifty-one outpatient asthmatics (84 women and 67 men) completed the Spanish versions of the Asthma Quality of Life questionnaire (AQL), as well as anxiety and depression inventories. A full history, physical examination, and pulmonary function test were performed on all subjects. Patients were classified into one of four asthma severity categories foll…

AdultMalePulmonary and Respiratory Medicinemedicine.medical_specialtyAdolescentPhysical examinationmacromolecular substancesSeverity of Illness IndexPulmonary function testingSex FactorsQuality of lifeSeverity of illnessmedicineHumansImmunology and AllergyDepression (differential diagnoses)AsthmaDepressive Disordermedicine.diagnostic_testbusiness.industryRespiratory diseaseMiddle Agedmedicine.diseaseAnxiety DisordersAsthmarespiratory tract diseasesDyspneaPediatrics Perinatology and Child HealthQuality of LifePhysical therapyAnxietyFemalemedicine.symptombusinessClinical psychologyJournal of Asthma
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Additional file 1: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

2016

Supplementary Table S1. Maximal percentage of inhibition of IL-8, MMP-9, CCL-5, GM-CSF and IL-1β release from neutrophils of healthy subjects and COPD patients. Neutrophils were incubated with aclidinium (Acl; 0.1nM-1 μM), fluticasone (Flut; 0.1nM-1 μM), formoterol (Form; 0.01nM-100nM) or salmeterol (Salm; 0.1nM-1 μM) in response to LPS (1 μg/ml) or cigarette smoke extract (CSE 5 %). The levels of different cytokines in the cell supernatant were determined and the maximal percent of inhibitions were calculated. Values are mean ± SD of 3 independent experiments run in triplicate. *p 

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Additional file 2: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

2016

Supplementary Figure E1. Effects of formoterol and salmeterol on pro-inflammatory markers. Concentration-dependent inhibition of lipopolysaccharide (LPS)-induced cytokines or MMP-9 release by formoterol (Form) and salmeterol (Salm) from peripheral blood neutrophils of healthy subjects and COPD patients. Neutrophils were preincubated with Salm (0.1nM-1 μM) or form (0.01nM-100nM) for 1 h followed by cell stimulation with LPS (1 μg/ml) for 6 h. Results are expressed as means ± SD of n = 3 (3 cell healthy and 3 cell COPD populations run in triplicate) independent experiments. Two-way ANOVA was followed by the post hoc Bonferroni test. *p 

respiratory tract diseases
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