A5024080563- Asthma and respiratory diseases
- Nitric Oxide and Endothelin Effects
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Phosphodiesterase function and regulation
- Respiratory and Cough-Related Research
- Ion channel regulation and function
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Pulmonary Hypertension Research and Treatments
- Neuroscience of respiration and sleep
- Mast cells and histamine
- Neonatal Respiratory Health Research
- Eicosanoids and Hypertension Pharmacology
- Pharmacological Effects and Assays
- Glycosylation and Glycoproteins Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neuroendocrine regulation and behavior
- Atherosclerosis and Cardiovascular Diseases
- Inflammatory mediators and NSAID effects
- Chemokine receptors and signaling
- Pneumonia and Respiratory Infections
- Aldose Reductase and Taurine
- Renin-Angiotensin System Studies
Universitat de València
2011-2024
INCLIVA Health Research Institute
2011-2024
Instituto de Salud Carlos III
2008-2019
Universitat Politècnica de València
2018
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
2009-2018
Centro de Investigación Biomédica en Red
2009-2016
Centro de Cirugía de Mínima Invasión Jesús Usón
2014
Ministry of Health
2007-2012
Hospital de Manises
2012
Hospital Clínico Universitario de Valencia
2007-2012
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer activator of transcription 3 (STAT3) protein activated in lung fibroblasts alveolar type II cells (ATII), thereby contributing to IPF. Although activation Janus kinase 2 (JAK2) has been implicated proliferative disorders, its role IPF unknown. aim this study was analyze JAK2 IPF, determine whether JAK2/STAT3 inhibition a potential therapeutic...
The incidence of cardiovascular diseases in premenopausal women is lower than men or postmenopausal women. This study reports the discovery a low grade systemic inflammation, including monocyte adhesion to arterial endothelium, elicited by menopause estrogen depletion. Chronic treatment with dose 17-beta-estradiol inhibition renin-angiotensin system reduced this inflammation. Using an vitro flow chamber human and venous endothelial cells, we found that leukocytes from healthy were more...
<h3>Background</h3> Idiopathic pulmonary fibrosis (IPF) is characterised by the aberrant epithelial to mesenchymal transition (EMT) and myofibroblast accumulation. Sphingosine-1-phosphate (S1P) sphingosine kinase 1 (SPHK1) have been implicated in lung transition, but their role EMT expression patients with IPF unknown. <h3>Methods results</h3> S1P levels were measured serum (n=27) bronchoalveolar lavage (BAL; n=15) from controls (n=30 for n=15 BAL studies). SPHK1 was tissue (n=12) (n=15)....
Aclidinium bromide is a novel potent, long-acting inhaled muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease. showed subnanomolar affinity five human receptors (M<sub>1</sub>–M<sub>5</sub>). [<sup>3</sup>H]Aclidinium dissociated slightly faster from M<sub>2</sub> and M<sub>3</sub> than [<sup>3</sup>H]tiotropium but much more slowly [<sup>3</sup>H]ipratropium. Its association rate receptor was similar to [<sup>3</sup>H]ipratropium 2.6 times...
Angiotensin II (Ang II) is implicated in the development of cardiac ischemic disorders which prominent neutrophil accumulation occurs. Ang can be generated intravascularly by renin-angiotensin system or extravascularly mast cell chymase. In this study, we characterized ability to induce accumulation.Intraperitoneal administration (1 nmol/L) induced significant recruitment within 4 hours (13.3+/-2.3x10(6) neutrophils per rat versus 0.7+/-0.5x10(6) control animals), disappeared 24 hours....
The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin-induced lung injury were explored in 'preventive' and 'therapeutic' protocols compared with glucocorticoids.Roflumilast (1 5 mg.kg(-1).d(-1), p.o.) or dexamethasone (2.5 was given to C57Bl/6J mice from day 1 14 (preventive) 7 21 (therapeutic) after intratracheal bleomycin (3.75 U.kg(-1)). In Wistar rats, roflumilast methylprednisolone (10 10 (therapeutic), following instillation (7.5 Analyses performed at the...
Abstract Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- trans (t)-resveratrol (RESV) two vivo models vascular inflammation identifies cardioprotective mechanisms that underlie them. In vivo, Ang-II–induced arteriolar leukocyte adhesion was inhibited by 71% t-RESV (2.1 mg/kg, i.v.), but not affected cis-RESV. Because estrogens influence rennin-angiotensin system, chronic treatment with (15...
Background Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends poor prognosis. Recent studies using vasodilators approved for PH have failed improving IPF mainly due to ventilation ( V )/perfusion Q ) mismatching oxygen desaturation. Janus kinase type 2 (JAK2) non-receptor tyrosine activated by broad spectrum of profibrotic vasoactive mediators, but its role associated unknown. Objective The study JAK2 as potential target treat...
This study examines the activity of antioxidant N ‐acetylcysteine on bleomycin‐induced pulmonary fibrosis in rats with emphasis early inflammatory phase. Rats receiving (300 mg kg −1 day , intraperitoneal) had less augmented lung wet weight, and lower levels proteins, lactate dehydrogenase, neutrophil macrophage counts bronchoalveolar lavage fluid myeloperoxidase a betterment histological score at 3 days postbleomycin. A diminished GSH/GSSG ratio lipid hydroperoxides were observed These...
We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDEIV) in relaxation human bronchus and guinea‐pig trachea vitro guinea‐pigs vivo . Functional studies showed that selective PDE inhibitors, rolipram denbufylline, relaxed preparations Two clinically used xanthine non‐selective theophylline pentoxifylline, were also effective these preparations, but much less potent than agents used. The rank order potency for four inhibitors both species was similar. Biochemical...
Abstract Angiotensin II (Ang-II) is associated with atherogenesis and arterial subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang-II causes the initial attachment of cells to arteriolar endothelium. now report on contribution CC chemokines this response. Intraperitoneal administration 1 nM induced MCP-1, RANTES, MIP-1α generation, maximal at 4 h, followed by recruitment 8 24 h. Using intravital microscopy within rat mesenteric microcirculation h after exposure...
Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect of N -acetylcysteine (NAC) on bleomycin-induced lung fibrosis rats. NAC (3 mmol·kg −1 ; oral) was given daily from 1 week prior to a single intratracheal instillation bleomycin (2.5 U·kg ) or saline, until 14 days postinstillation. partially decreased augmented collagen deposition bleomycin-exposed rats (hydroxyproline content 4,354±386 and...
Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect aclidinium, a new long-acting muscarinic antagonist, on expression in human airway epithelial cells. mRNA (RT-PCR) protein (ELISA immunohistochemistry) were studied bronchial tissue differentiated cells activated with carbachol (100 μM) or cigarette smoke extract absence presence aclidinium. Carbachol increased bronchus...
<h3>Background</h3> Fibroblast to myofibroblast transition is believed contribute airway remodelling in lung diseases such as asthma and chronic obstructive pulmonary disease. This study examines the role of aclidinium, a new long-acting muscarinic antagonist, on human fibroblast transition. <h3>Methods</h3> Human bronchial fibroblasts were stimulated with carbachol (10<sup>−8</sup> 10<sup>−5</sup> M) or transforming growth factor-β1 (TGF-β1; 2 ng/ml) presence absence aclidinium...
Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be therapeutic value. Clinical work indicates that N ‐acetylcysteine (NAC) beneficial this disease. The activity antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression rats. NAC (3 mmol·kg −1 ·day ) or saline given orally to Sprague-Dawley rats for 1 week prior a single intratracheal instillation bleomycin (2.5 U·kg 14 days...
Background: Infection remains a drawback of parenteral nutrition (PN), probably related, among other factors, to immunosuppressive effects its lipid component. Newer preparations may have lesser impact. This study examines the an olive oil–based emulsion (long‐chain triacylglycerols‐monounsaturated fatty acids [LCT‐MUFA]; ClinOleic) on various functions human neutrophils in vitro and rat leukocyte–endothelial cell interactions vivo compared with LCT (Intralipid) 50% LCT–50% medium‐chain...
The present study addressed the effects of investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo vitro.In vivo, intravital video-microscopy was used to determine p.o. microvascular rat mesenteric venules. In vitro, N-oxide, active metabolite humans, other inhibitors neutrophil adhesion tumour necrosis factor alpha (TNFalpha)-activated human umbilical vein cells (HUVEC), E-selectin expression thrombin-induced evaluated. Flow...
Abstract Activation of the nuclear receptor PPARb/d inhibits acute inflammatory responses in vitro with human primary cells and vivo by targeting endothelial cell-leukocyte interaction. The infiltration PMNs into tissues is a prominent feature inflammation. mechanism underlying PMN recruitment depends on release chemotactic mediators CAM expression cells. PPARβ/δ widely expressed many tissues, including vascular endothelium; however, its role inflammation remains unclear. Using intravital...