Effect of thromboxane antagonists on ozone-induced airway responses in dogs

1990 ◽  
Vol 69 (3) ◽  
pp. 880-884 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
P. M. O'Byrne

Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.

1994 ◽  
Vol 76 (4) ◽  
pp. 1583-1588 ◽  
Author(s):  
W. H. Stevens ◽  
C. G. Lane ◽  
M. J. Woolley ◽  
R. Ellis ◽  
P. Tagari ◽  
...  

We used the 5-lipoxygenase-activating protein (FLAP) antagonist MK-0591 to investigate the importance of leukotrienes (LT) in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs. Six random source dogs were studied. On one day, dogs were treated with MK-0591 (2 mg/kg iv) followed by a continuous intravenous infusion of 8 micrograms.kg-1.min-1. On the other day, the diluent was infused. Acetylcholine airway responsiveness was measured before and 1 h after ozone inhalation (3 ppm for 30 min). On each day, whole blood and bronchoalveolar lavage (BAL) cells were challenged with calcium ionophore to stimulate LTB4 production. Urinary LTE4 levels were measured before and after ozone. MK-0591 inhibited LTB4 production in whole blood by 96% (P = 0.001) and that from BAL cells by 91% (P = 0.001). By contrast, MK-0591 had no effect on ozone-induced bronchoconstriction, airway hyperresponsiveness, or influx of neutrophils into BAL. The mean log difference of the pre- to post-acetylcholine provocative concentration was 0.64 +/- 0.40 during MK-0591 treatment and 0.68 +/- 0.40 during diluent treatment (P = 0.71). These results indicate that peptidoleukotrienes are produced during ozone inhalation and that MK-0591 inhibits LT production in dogs. However, LTs do not play a role in ozone-induced bronchoconstriction, airway inflammation, or airway hyperresponsiveness in dogs.


1987 ◽  
Vol 63 (3) ◽  
pp. 1174-1179 ◽  
Author(s):  
G. L. Jones ◽  
C. G. Lane ◽  
P. J. Manning ◽  
P. M. O'Byrne

Airway hyperresponsiveness develops in dogs after ozone inhalation. This study examined the role of the parasympathetic nervous system in ozone-induced airway hyperresponsiveness in dogs. Dose-response curves to acetylcholine (n = 8) and histamine (n = 4) were measured before and after exposure to ozone (3 ppm for 30 min). The provocative concentration of each agonist was measured on two randomly assigned days separated by at least 1 wk. On one day a control experiment was performed, and on the other day the dogs were pretreated with the ganglionic blocker hexamethonium bromide in doses that block ganglionic transmission. The acetylcholine provocative concentration decreased on the control day from 5.5 mg/ml (%SE 1.8) before ozone to 0.5 mg/ml (%SE 2.0) after ozone (P less than 0.0001). After pretreatment with hexamethonium the acetylcholine provocative concentration decreased from 9.0 mg/ml (%SE 1.8) before ozone to 1.0 mg/ml (%SE 2.0) after ozone (P = 0.002). The results were similar when histamine was used as the agonist. Therefore, ganglionic blockade does not prevent airway hyperresponsiveness after ozone inhalation, and a parasympathetic reflex mechanism is not responsible for airway hyperresponsiveness after ozone inhalation in dogs.


2018 ◽  
Vol 69 (8) ◽  
pp. 2232-2235
Author(s):  
Marius Moga ◽  
Mark Edward Pogarasteanu ◽  
Antoine Edu

The role of arthroscopy in incipient and mild arthrosis, even combined with proximal tibial ostetomy, is well known and well documented. On the other hand, its role in the treatment of advanced arthrosis of the large joints, especially the knee, is a subject of controversy. The proponents of the use of arthroscopy in advanced arthrosis claim that meniscectomy, synovectomy, ostophytectomy, chondral lesion stabilization, arthroscopic release, plica and loose body removal greatly improve the quality of life for most patients, especially if followed by the use of viscoelastic injection, by diminishing pain and improving joint range of motion. The opponents claim that, even though the advantages are clear in the cases that refuse arthroplasty, in all the other cases the surgical indication should be total knee arthroplasty, as the clinical relief is temporary, but with all the risks of a surgical intervention. We have conducted an overview of the recent literature, in order to find objective evidence to sustain either point of view. We focused on articles published that included an objective measurement of before and after clinical status through clinical scores and objective measurements. We also focused on the follow-up period and on the evolution of the pathology after arthroscopy.


2002 ◽  
Vol 283 (1) ◽  
pp. L198-L204 ◽  
Author(s):  
Jane M. Schuh ◽  
Kate Blease ◽  
Steven L. Kunkel ◽  
Cory M. Hogaboam

Eotaxin/CCL11 is a major chemoattractant for eosinophils and Th2 cells. As such, it represents an attractive target in the treatment of allergic disease. The present study addresses the role of eotaxin/CCL11 during acute and chronic allergic airway responses to the fungus Aspergillus fumigatus. Mice lacking the eotaxin gene (Eo−/−) and wild-type mice (Eo+/+) were sensitized to A. fumigatus and received either an intratracheal challenge with soluble A. fumigatusantigens (acute model) or an intratracheal challenge with live A. fumigatus spores or conidia (chronic model). Airway hyperresponsiveness and eosinophil, but not T cell, recruitment were significantly decreased at 24 h after the soluble allergen in A. fumigatus-sensitized Eo−/− mice compared with similarly sensitized Eo+/+ mice. In contrast, the development of chronic allergic airway disease due to A. fumigatus conidia was not altered by the lack of eotaxin. Together, these data suggest that eotaxin initiates allergic airway disease due to A. fumigatus, but this chemokine did not appear to contribute to the maintenance of A. fumigatus-induced allergic airway disease.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ali Abdulkareem Al-Shabkhon ◽  
Adel Ahmed Halim Emam ◽  
Ahmed Abd Elfattah Afify

Abstract Background Immunologic background of vitiligo, role of vitamin D on its pathogenesis, role of NB-UVB on its treatment and its stimulatory effect NB-UVB on VDR expression are challenging area of research. The current study will focus on evaluating the effect of NB-UVB on serum and tissue level of vitamin D in vitiligo patients and correlating it with the degree of improvement. Aim of the study The aim of the present study is to evaluate and compare the serum and tissue vitamin D level in vitiligo patients before and after NB- UVB therapy and correlate them together and with the degree of improvement. Patients and methods A case-control study included 16 vitiligo patients and 16 age and sex matched healthy controls. All patients will be examined by one dermatologist (demonstrating the extent of depigmentation according to rule of nines), and photographs will be taken before and after phototherapy to be evaluated by two different dermatologists to document the extent of repigmentation. Estimation of serum level of vitamin D by ELISA Results Five of the 15 patients achieved more than 55% repigmentation; the mean duration of disease was 13 months. The remaining 10 patients had 30% - 40% repigmentation.


2002 ◽  
Vol 282 (1) ◽  
pp. L44-L49 ◽  
Author(s):  
Brian Morse ◽  
Joseph P. Sypek ◽  
Debra D. Donaldson ◽  
Kathleen J. Haley ◽  
Craig M. Lilly

Levels of interleukin (IL)-13 are increased in asthmatic airways. IL-13 has been shown to be necessary and sufficient for allergen-induced airway hyperresponsiveness and increased inflammatory cell counts in bronchoalveolar lavage (BAL) fluid in a murine model of asthma but is thought to protect against airway inflammation when low doses are provided to the guinea pig lung. To determine the role of IL-13 in the guinea pig, we studied the effects of a 360-μg/kg dose of nebulized IL-13 in naive animals and of IL-13 abrogation after airway challenge of sensitized animals. Nebulized IL-13 significantly decreased the dose of histamine required to double baseline respiratory system resistance (ED100, 22 ± 3 vs. 13 ± 2 nmol/kg; P < 0.05) and was associated with recovery of significantly greater numbers of macrophages, lymphocytes, eosinophils, and neutrophils in BAL fluid. Guinea pigs pretreated with a fusion protein that binds IL-13 [soluble IL-13 receptor α2 (sIL-13Rα2)] were protected from developing antigen-induced airway hyperresponsiveness (ED100, 210 ± 50 vs. 20 ± 10 nmol/kg; P <0.01). sIL-13Rα2 (2 doses of 20 mg/kg) significantly reduced the histological grade of allergen-induced lung eosinophil accumulation, whereas the effects of two doses of 10 mg/kg were not significant. These findings demonstrate that the tissue levels of IL-13 induced by allergen challenge of sensitized animals induce airway hyperresponsiveness and inflammation and that IL-13 is required for the expression of allergen-induced airway hyperresponsiveness in the guinea pig ovalbumin model.


2012 ◽  
Vol 24 (3) ◽  
pp. 229-248
Author(s):  
Tim Carter

AbstractBy the last quarter of the eighteenth century, the typical Metastasian two-stanza aria text could be set to music in one of two ways: in the ternary form typical of the earlier da capo aria (stanzas 1–2–1) or in a binary one (stanzas 1–2–1–2). Why did Mozart choose one form over the other in Idomeneo (1781); what does this tell us about the role of his librettist, Giovanni Battista Varesco, both before and after the composer left Salzburg for Munich to finish composing the opera and to prepare its performance; and how might these issues enable some rational inquiry into questions of music and drama?


1997 ◽  
Vol 83 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Zhong-Xin Wu ◽  
Robert F. Morton ◽  
Lu-Yuan Lee

Wu, Zhong-Xin, Robert F. Morton, and Lu-Yuan Lee. Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs. J. Appl. Physiol. 83(3): 958–965, 1997.—Acute exposure to ozone (O3) induces airway hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (Rl) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (ΔRl= 67 ± 19%, ΔCdyn = −29 ± 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (ΔRl = 620 ± 224%, ΔCdyn = −35 ± 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of Rl and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.


1981 ◽  
Vol 61 (6) ◽  
pp. 781-784 ◽  
Author(s):  
J. Savoy ◽  
S. Dhingra ◽  
N. R. Anthonisen

1. in 10 patients with pulmonary fibrosis and in seven control subjects, we measured the pressure at the mouth 0.1 s after onset of an inspiration against occluded airway (P0.1), minute ventilation (VI), breathing frequency (fr), tidal volume (VT), inspiratory duration (Tl) and calculated the mean inspiratory flow (VT/Tl) and the fraction of the breath cycle devoted to inspiration (Tl/Ttot.). in the patients measurements were made at normal arterial oxygen saturations (Sao2), before and after lignocaine airway anaesthesia. 2. Efficacy of airway anaesthesia was tested by the cough response to citric acid inhalation. 3. in pulmonary fibrosis P0.1, f1 and VT/Tl were greater than in the control subjects, VT and Tl, were smaller and Tl/Ttot. and VI were not different. 4. Effective airway anaesthesia did not modify P0.1 and breathing pattern parameters observed in pulmonary fibrosis. 5. These results suggest that airway receptors do not contribute to a major extent to the control of breathing in pulmonary fibrosis.


2019 ◽  
Vol 7 (3) ◽  
pp. 99-104 ◽  
Author(s):  
Farzaneh Rassam ◽  
Leila Khedmat ◽  
Farnaz Khatami

Introduction: The increasing prevalence of overweight and obesity is one of the most critical issues of urban health. The current study investigated the effects of community-based interventions on modification of overweight and obesity. Methods: A program based on the Urban Health Equity Assessment and Response Tool (Urban HEART) was developed and implemented in 2013-2014. A total of 166 Iranian females aged 15 years or older who were classified as overweight or obese using body mass index (BMI) were randomly selected and gave verbal consent to participate in this study. The intervention was carried out for a duration of 4 months. Results: The mean age of subjects was 43.6±12.2 years. The total number of overweight and obese individuals were 75 (45.2%) and 91 (54.8%), respectively. The mean BMI of the patients before and after the intervention was 30.3±2.7 and 29.4±2.7 kg/m2 , respectively (P < 0.05). Higher education level and greater floor area were recognized as valid predictors for reduced BMI after the intervention (P < 0.001). Conclusion: This study successfully represents the collaborative role of the community in improving health status by reducing overweight and obesity. The Urban HEART provided distinct opportunities for presenting the promising results of interventions to health policymakers and managers so they can adjust macro and micro policies for achieving better community health outcomes.


Sign in / Sign up

Export Citation Format

Share Document