0000000000124119
AUTHOR
J. L. Ortiz
Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary endothelial cells under oxidative stress.
Several clinical studies have shown that smoking in asthmatics and chronic obstructive pulmonary disease patients is closely associated with corticosteroid refractoriness. In this work, we have analyzed glucocorticoid insensitivity in human pulmonary artery endothelial cells (HPAECs) under cigarette smoke extract (CSE) exposure as well as the possible additive effects of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were measured by colorimetric assays and enzyme immunoassay, respectively. PDE4 isotypes and glucocorticoid rec…
Effects of low temperature and pharmacological interventions on the responses of the isolated guinea-pig trachea
Cooling the guinea-pig isolated trachea from 37°C to 20°C virtually abolished the response to CaCl2 (in K+-depolarized tissues) and depressed that to histamine (about 75% reduction), KCl and 5-hydroxytryptamine (around 50% inhibition) while the response to acetylcholine remained unaffected. A further cooling to 10°C was necessary to inhibit acetylcholine-induced contractions. Hyporesponsiveness to spasmogens by cooling was not associated with subsensitivity (increased EC50) except for 5-hydroxytryptamine. Contractile responses to KCl (50 mmol/l), histamine (1 mmol/l) and 5-hydroxytryptamine (0.1 mmol/l) in a Ca2+-free EGTA (0.1 mmol/l)-containing solution were inhibited by cooling to 20°C b…
Relaxation by Calcium Antagonists of Potassium-contracted Trachea from Normal and Sensitized Guinea-pigs: Influence of Epithelium and the Surface of Drug Entry
Abstract A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K+-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact…
LEUKOTRIENE RECEPTORS ON HUMAN PULMONARY VASCULAR ENDOTHELIUM
1. Cysteinyl-leukotrienes cause contractions and/or relaxations of human isolated pulmonary vascular preparations. Although, the localization and nature of the receptors through which these effects are mediated have not been fully characterized, some effects are indirect and not mediated via the well-described LT1 receptor. 2. In human pulmonary veins (HPV) with an intact endothelium, leukotriene D4 (LTD4) induced contraction above basal tone. This response was observed at lower concentrations of LTD4 in the presence of nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NOARG). Contractions (in the absence and presence of L-NOARG) were partially blocked by the LT1 antagonists (MK 5…
Effects of dantrolene on the responses to methylxanthines in the isolated guinea-pig trachea.
The effect of dantrolene on the responses to methylxanthines (caffeine and theophylline) and a beta-adrenoceptor agonist (salbutamol) was studied in isolated guinea-pig trachea. Caffeine and theophylline (1 microM-10 mM) and salbutamol (1 nM-10 microM) produced concentration-dependent relaxation of spontaneous and stimulated (acetylcholine 1 mM) tone. Responses to high concentrations (10 mM) of caffeine and theophylline added to tracheal strips either unstimulated (spontaneous tone) or indomethacin (2.8 microM)-treated were reversed to contractions in the presence of dantrolene (3 microM-0.3 mM). This effect was not observed for salbutamol or when relaxant responses to the agonists were gen…
ROLIPRAM INHIBITS PAF-INDUCED AIRWAY MICROVASCULAR LEAKAGE IN GUINEA-PIG - A COMPARISON WITH MILRINONE AND THEOPHYLLINE
The effects of 3 phosphodiesterase (PDE) inhibitors, rolipram (PDE IV), milrinone (PDE III) and theophylline (non-selective) on PAF (50 ng kg-1; iv)-induced airway vascular leakage have been evaluated in guinea-pigs. Rolipram (3-300 micrograms kg-1; iv) reduced the increase in permeability induced by PAF at all airway levels whereas milrinone (10-1000 micrograms kg-1; iv) and theophylline (30 mg kg-1; iv) were without effects. The anti-leakage activity of rolipram may be of therapeutic value in asthma.
Young, active radio stars in the AB Doradus moving group
Context. Precise determination of stellar masses is necessary to test the validity of pre-main-sequence (PMS) stellar evolutionary models, whose predictions are in disagreement with measurements for masses below 1.2 M. To improve such a test, and based on our previous studies, we selected the AB Doradus moving group (AB Dor-MG) as the best-suited association on which to apply radio-based high-precision astrometric techniques to study binary systems. Aims. We seek to determine precise estimates of the masses of a set of stars belonging to the AB Dor-MG using radio and infrared observations. Methods. We observed in phase-reference mode with the Very Large Array (VLA) at 5 GHz and with the Eur…
Effects of Calcium Antagonists on Rat Normal and Skinned Fundus
Abstract Calcium chloride (CaCl2) (0·1−25 Mm, in K+-depolarized tissue), KCl (10−112 Mm) and acetylcholine (1 × 10−9 m−1 Mm) produced concentration-dependent contractions of rat isolated fundus. Verapamil (0·01−100 μm), cinnarizine (1−100 μm), trifluoperazine (10−500 μm) and dantrolene (50−250 μm) each produced a concentration-related rightward and downward shift of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (25 Mm)-induced contraction of depolarized fundus, was verapamil (2.5 μm) > cinnarizine (8·7 μm) > trifluoperazine (85·1 μm) > dantrolene (> 250 μm). Cinnarizine (0·5 Mm) a…
Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences
BACKGROUND AND PURPOSE Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH ETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phal…
β-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E 2 -inhibitory effects in human neutrophils
Human neutrophils were treated for 4 h with a combination of salbutamol (1 µM), a β2-adrenoceptor agonist, and rolipram (30 µM), a selective phosphodiesterase 4 inhibitor, to investigate whether this treatment produces up-regulation of phosphodiesterase activity with functional consequences. Anion-exchange chromatography coupled with the use of selective activators and inhibitors demonstrated that a phosphodiesterase activity with characteristics of the isoenzyme type 4 was increased in drug-treated cells. Kinetic analysis showed a ~1.5-fold increase in V max without alteration of K m values. The augmented phosphodiesterase activity in drug-treated cells was abolished by actinomycin D. Cycl…
The large trans-Neptunian object 2002 TC 302 from combined stellar occultation, photometry, and astrometry data
All authors: Ortiz, J. L.; Santos-Sanz, P.; Sicardy, B.; Benedetti-Rossi, G.; Duffard, R.; Morales, N.; Braga-Ribas, F.; Fernández-Valenzuela, E.; Nascimbeni, V.; Nardiello, D.; Carbognani, A.; Buzzi, L.; Aletti, A.; Bacci, P.; Maestripieri, M.; Mazzei, L.; Mikuz, H.; Skvarc, J.; Ciabattari, F.; Lavalade, F. Scarfi, G.; Mari, J. M.; Conjat, M.; Sposetti, S.; Bachini, M.; Succi, G.; Mancini, F.; Alighieri, M.; Dal Canto, E.; Masucci, M.; Vara-Lubiano, M.; Gutiérrez, P. J.; Desmars, J.; Lecacheux, J.; Vieira-Martins, R.; Camargo, J. I. B.; Assafin, M.; Colas, F.; Beisker, W.; Behrend, R.; Mueller, T. G.; Meza, E.; Gomes-Junior, A. R.; Roques, F.; Vachier, F.; Mottola, S.; Hellmich, S.; Campo …
Non-specific Hyperreactivity to Pharmacological Stimuli in Tracheal and Lung Parenchymal Strips of Actively Sensitized Guinea-pigs
Abstract The responsiveness of tracheal and lung parenchymal strips isolated from actively sensitized guinea-pigs to CaCl2 (in K+-depolarized tissue), KCl, acetylcholine and histamine was compared with that of strips from unsensitized animals. The concentration-response curves to the mentioned agonists exhibited, in the sensitized group, a left upward displacement (greater maximal effect, lesser effective concentration 50% and a steeper slope) compared with those obtained in the unsensitized group. These results indicate the existence of a non-specific increase in responsiveness in the airway smooth muscle from sensitized animals.
Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils.
Objective: To investigate whether histamine produces up-regulation of phosphodiesterase (PDE) activity with functional consequences in human peripheral blood neutrophils.¶Methods: PDE activity was studied by a radioisotopic method following anion-exchange chromatography. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of mRNA transcripts of PDE4 subtypes. Cyclic AMP (cAMP) levels were measured by enzyme-immunoassay, and superoxide generation by cytochrome c reduction.¶Treatment: Neutrophils were incubated for 4 h with histamine (1 μM).¶Results: PDE4 was the only isoenzyme activity increased in treated neutrophils. Kinetic analysis showed a ∼1.5-fold increase …
The 2017 May 20 stellar occultation by the elongated centaur (95626) 2002 GZ32
Full list of authors: Santos-Sanz, P.; Ortiz, J. L.; Sicardy, B.; Benedetti-Rossi, G.; Morales, N.; Fernández-Valenzuela, E.; Duffard, R.; Iglesias-Marzoa, R.; Lamadrid, J. L.; Maícas, N.; Pérez, L.; Gazeas, K.; Guirado, J. C.; Peris, V.; Ballesteros, F. J.; Organero, F.; Ana-Hernández, L.; Fonseca, F.; Alvarez-Candal, A.; Jiménez-Teja, Y. Vara-Lubiano, M.; Braga-Ribas, F.; Camargo, J. I. B.; Desmars, J.; Assafin, M.; Vieira-Martins, R.; Alikakos, J.; Boutet, M.; Bretton, M.; Carbognani, A.; Charmandaris, V.; Ciabattari, F.; Delincak, P.; Fuambuena Leiva, A.; González, H.; Haymes, T.; Hellmich, S.; Horbowicz, J.; Jennings, M.; Kattentidt, B.; Kiss, Cs; Komžík, R.; Lecacheux, J.; Marciniak, …
Responses to histamine and selective H2-receptor agonists in lung parenchymal strips from normal and sensitized guinea-pigs.
Histamine produces concentration-dependent contractions of lung parenchyma strips obtained from normal and sensitized guinea-pigs. The responsiveness of the sensitized lung strips to histamine was significantly increased compared to normal tissues. Clemizole (0.1 microM) was equally effective as an H1-antagonist in normal (dose-ratio 9.12) and sensitized (dose-ratio 9.77) tissues. The concentration-response curves to histamine were displaced to the left by cimetidine (0.1 microM to 0.1 mM) with similar dose-ratios in normal and sensitized tissues. Cimetidine enhanced maximal responses to histamine only in normal lung strips. The effects of submaximal equieffective concentrations of histamin…
Effect of dantrolene sodium in isolated guinea-pig trachea.
The effect of dantrolene sodium (3 microM-0.3 mM) on the spontaneous tone and responses to various contractile agonists was studied in isolated guinea-pig trachea. Dantrolene produced a concentration-related inhibition of the spontaneous tracheal tone, reaching a value of 94.8 +/- 4.8% of the relaxation induced by caffeine 10 mM. Removal of the epithelium did not affect the dantrolene-induced relaxation. Dantrolene did not alter the concentration-response curve for KCl and produced only small displacements of the concentration-response curves for CaCl2, acetylcholine and histamine, without affecting their maximal effects. Dantrolene dose relatedly inhibited the contraction induced by caffei…
COOLING-INDUCED CONTRACTION OF TRACHEA ISOLATED FROM NORMAL AND SENSITIZED GUINEA-PIGS
Fast (−7°C/min) cooling of guinea-pig isolated trachea produced a rapidly developing, transient contraction followed by relaxation. Cooling-induced contraction was dependent on temperature (30, 20 or 10°C) and responses in trachea obtained from actively sensitized guinea pigs were significantly greater (20 and 10°-C) than those observed in normal trachea. Cooling to 20°C was selected for subsequent experiments. Pre-treatment with sufficient concentrations of atropine, clemastine, cromoglycate, indomethacin, or nordihydroguaiaretic acid did not depress contraction to cooling in either normal or sensitized trachea. This indicates a direct effect of cooling. The contraction. produced by coolin…
EFFECTS OF CROMAKALIM (BRL-34915) IN TRACHEA ISOLATED FROM ACTIVELY SENSITIZED GUINEA-PIGS
Abstract The effects of cromakalim were examined in tracheal strips isolated from normal (unsensitized) guinea-pigs and from animals actively sensitized to bovine serum albumin. Sensitized tracheae exhibited hyper-responsiveness to KCl, acetylcholine and histamine. In normal and sensitized tracheae, cromakalim (0·01–10 μm) produced a concentration-related suppression of spontaneous tone. The ability of cromakalim to relax tracheal strips was reduced when tone was raised by KCl (25 Mm), acetylcholine (0·1 Mm) or histamine (0·1 Mm) and lost against KCl (120 Mm)-induced spasm. Procaine (5 Mm) abolished the relaxant effect of cromakalim whilst tetraethylammonium (8 Mm) was without effect. These…