dinoprost and Hypersensitivity

Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown.. (1) To study the effect of montelukast, a LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with asthma and atopic children; (2) to measure exhaled nitric oxide.. An open-label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in 17 atopic children with asthma and 16 atopic children without asthma.. Pretreatment exhaled LTE(4) (P < .0001) and 8-isoprostane (P < .0001) values were higher in atopic children with asthma than in atopic children without asthma. In atopic children with asthma, montelukast reduced exhaled LTE(4) by 33% (P < .001), and this reduction was correlated with pretreatment LTE(4) values (r = -0.90; P = .0001). Posttreatment exhaled LTE(4) levels in children with asthma were higher than pretreatment LTE(4) values in atopic children without asthma (P < .004). Montelukast had no effect on exhaled LTE(4) in atopic children without asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P = .94; atopic children without asthma, P = .55) and PGE(2) (atopic children with asthma, P = .56; atopic children without asthma, P = .93) in both groups. In atopic children with asthma, exhaled nitric oxide concentrations were reduced by 27% (P < .05) after montelukast.. Leukotriene receptor antagonists decrease exhaled LTE(4) in atopic children with asthma. This reduction is dependent on baseline exhaled LTE(4) values.. Measurement of exhaled LTE(4) might help identify children with asthma most likely to benefit from LTRAs.

Topics: Acetates; Allergens; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Child; Cross-Sectional Studies; Cyclopropanes; Dinoprost; Dinoprostone; Humans; Hypersensitivity; Leukotriene Antagonists; Leukotriene E4; Nitric Oxide; Quinolines; Skin Tests; Spirometry; Sulfides

The dose-response (dose, 0.01, 0.05, 0.1, 0.5, 1, and 5 mg) profiles of 10 atopic and 10 nonatopic subjects were determined for nasal patency, secretion weight, pulmonary function, eustachian tube function, middle-ear function, and symptoms after intranasal inhalation challenges with histamine, bradykinin, methacholine, prostaglandin D2, and prostaglandin F2 alpha (PGF2 alpha). Results demonstrated that challenge with PGF2 alpha increased nasal patency, whereas challenge with all other substances decreased patency. The relationship between substances in eliciting a nasal congestive response was prostaglandin D2 greater than histamine greater than bradykinin greater than methacholine. A similar effect ordering was noted for the postchallenge development of eustachian tube dysfunction. Secretion weights were significantly greater after challenge with histamine compared to all other substances. A decrease in pulmonary function was observed only after challenge with PGF2 alpha, although the effect was not statistically significant. No changes in middle-ear pressure were observed for challenges with any of the substances. Only histamine challenge provoked sneezing, whereas challenge with either of the prostaglandins provoked cough. With the exception of methacholine, all substances caused symptoms of rhinorrhea, congestion, and sore throat. Bradykinin was particularly effective in provoking "pain/pressure"-related symptoms. With the exception of secretion weight, the differences between responses of atopic and nonatopic subjects were not statistically significant. These results document mediator specificity in the physiologic and symptomatic responses to intranasal challenge.

Topics: Adolescent; Adult; Bradykinin; Dinoprost; Dose-Response Relationship, Drug; Ear; Forced Expiratory Volume; Histamine; Humans; Hypersensitivity; Male; Methacholine Chloride; Nasal Mucosa; Nasal Provocation Tests; Prostaglandin D2; Pulmonary Ventilation; Reference Values; Rhinitis

Mast cell (MC) mediators, among them prostaglandin D2 (PGD2) and 9α,11β-PGF2, PGD2's metabolite, play a key role in allergic reactions, including bee venom anaphylaxis (BVA). Assessment of these mediators has never been performed in BVA. The aim of the study was to assess the activation of MC during in vivo provocation with bee venom (BV) and to measure PGD2 and 9α,11β-PGF2 in the course of an allergen challenge. The second aim was to determine if assessment of these mediators could be useful for predicting adverse events during venom immunotherapy (VIT). In 16 BV-VIT patients and 12 healthy subjects, levels of PGD2 and 9α,11β-PGF2 were assessed during BV provocation by means of the skin chamber method. Chamber fluids, collected at 5 and 15 min, were analyzed for both mediators by gas chromatography mass spectrometry negative ion chemical ionization. BVA in comparison to non-allergic patients had a significantly higher ratio of 9α,11β-PGF2 in allergen-challenged chambers to 9α,11β-PGF2 in allergen-free chambers after 15 min of provocation (p = 0.039). Allergen challenge resulted in a significant increase of 9α,11β-PGF2 levels between 5 and 15 min after provocation only in BVA patients (p < 0.05). Analysis of log-transformed PGD2 levels showed significant difference between changes in PGD2 concentration between BVA and healthy subjects. No study patient developed adverse reactions during. 9α,11β-PGF2 is actively generated during the early allergic response to BV. Skin chamber seems to be a promising, non-invasive and safe model of in vivo allergen provocation in BV-allergic patients. High or low levels of both mediators do not predict occurrence of adverse events during VIT.

Topics: Adolescent; Adult; Aged; Allergens; Asthma; Bee Venoms; Biomarkers; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypersensitivity; Immunotherapy; Male; Mast Cells; Middle Aged; Multivariate Analysis; Prostaglandin D2; ROC Curve; Skin Tests; Young Adult

The importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs.. Guinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). The animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies.. Ovalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. The 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. The activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001).. In this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma. This functional alteration may be due to a high expression of 8-isoprostane, which had a procontractile effect. The mechanism involved in this response is likely related to the modulation of NF-kB expression, which contributed to the activation of the arginase and iNOS pathways. The association of both inhibitors potentiated the reduction of 8-isoprostane expression in this animal model.

Topics: Administration, Inhalation; Animals; Arginase; Chronic Disease; Dinoprost; Disease Models, Animal; Guinea Pigs; Hypersensitivity; Lung; Male; NF-kappa B; Nitric Oxide Synthase Type II; Ovalbumin; Oxidative Stress; Pneumonia; Respiratory Mechanics

To evaluate markers of mast cell and basophil activation in children undergoing the initial phase of honeybee venom immunotherapy (VIT).. Five children (four boys and one girl) aged 9.5-18 years with severe systemic bee sting reactions and confirmed IgE-mediated allergy were enrolled. Plasma and urine concentrations of 9α,11β-PGF2 and serum tryptase levels were measured at four time points and peripheral blood basophil count and CD63 expression were measured at three time points in the course of VIT, including 5-day rush initial immunotherapy (cumulative dose of 223 µg of bee venom allergen) and two subsequent maintenance doses of 100 µg.. In the first 40 days of VIT, there was a decrease in mean plasma levels of 9α,11β-PGF2 (from 41.5 to 27.9 pg/ml; p < 0.05), accompanied by an increase in baseline basophil activation (from 2 to 15%; p < 0.05). The median serum tryptase levels increased from 3.45 to 4.40 ng/ml during rush phase and subsequently returned to initial values (statistically not significant). In four patients, the basophil activation test in response to bee venom allergens remained positive throughout the study. The fifth patient was basophil activation test-negative at all three measurements, and a post hoc analysis revealed clinical peculiarities that are discussed in the paper.. Our preliminary results indicate that plasma levels of 9α,11β-PGF2 decrease while numbers of activated basophils increase during the initial phase of bee venom rush immunotherapy in children.

Topics: Adolescent; Basophils; Bee Venoms; Biomarkers; Cell Count; Cell Degranulation; Child; Desensitization, Immunologic; Dinoprost; Female; Humans; Hypersensitivity; Male; Mast Cells; Monitoring, Physiologic; Tetraspanin 30; Tryptases

Enhanced oxidative stress has been described in adults who suffer from symptoms of asthma and poor lung function. This study assessed the relation between markers of oxidative stress and antioxidant status and lung function, symptoms of asthma, atopy and bronchial hyperresponsiveness (BHR) in young adults.. A sub-sample of 589 individuals aged 22-28 years, selected from a total of 1232 included in a survey assessing early and current risk factors for chronic diseases, participated in the study. Participants were from an agricultural area of Chile, responded to a Spanish version of the European Community Respiratory Health Survey questionnaire, were skin tested to eight allergens, and challenged with methacholine to assess BHR. Five hundred and eighty-five individuals had measures of plasma biomarkers ferric reducing ability of plasma, uric acid, protein carbonyls and 564 had 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) assessed.. All participants had detectable plasma 8-iso-PGF(2alpha) and carbonyl levels. There was no indication for an association between markers of antioxidant status or oxidative stress with any of the outcomes studied.. The levels of oxidative stress-related biomarkers and antioxidant status in plasma may not be related to asthma in the general population in the absence of more severe symptoms or exacerbations.

Topics: Adult; Allergens; Antioxidants; Asthma; Biomarkers; Blood Proteins; Body Mass Index; Dinoprost; Female; Ferric Compounds; Forced Expiratory Volume; Humans; Hypersensitivity; Male; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Respiratory Function Tests; Respiratory Sounds; Uric Acid; Vital Capacity; Young Adult

We investigated the role of antioxidants in airway hyperresponsiveness to acetylcholine using young asthma model mice, which were sensitized and stimulated with ovalbumin.. The mice had been fed either a normal diet, an alpha-tocopherol-supplemented diet or a probucol-supplemented diet 14 days before the first sensitization. They were immunized with antigen at intervals of 12 days and, starting from 10 days after the second immunization, they were exposed to antigen 3 times every 4th day using an ultrasonic nebulizer. Twenty-four hours after the last antigen inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was collected. A blood and lung tissue study was also carried out.. Twenty-four hours after the last antigen challenge, both IL-4 and IL-5 in the BALF of alpha-tocopherol-supplemented mice were significantly decreased. The IL-5 level in probucol-supplemented mice was also decreased, but there was no difference in IL-4 levels. The serum IgE level was decreased in probucol-supplemented mice. Differential cell rates of the fluid revealed a significant decrease in eosinophils due to antioxidant supplementation. Airway hyperresponsiveness to acetylcholine was also repressed in antioxidant-supplemented mice. In histological sections of lung tissue, inflammatory cells and mucus secretion were markedly reduced in antioxidant-supplemented mice. We investigated the antioxidant effect on our model mice by examining 8-isoprostane in BALF and lung tissue, and acrolein in BALF; however, our experiment gave us no evidence of the antioxidant properties of either alpha-tocopherol or probucol contributing to the reduction of airway inflammation.. These findings indicate that alpha-tocopherol and probucol suppress allergic responses in asthma model mice, although these two drugs cause suppression in different ways that are unrelated to antioxidation.

Topics: Acrolein; Allergens; alpha-Tocopherol; Animals; Antioxidants; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Dietary Supplements; Dinoprost; Disease Models, Animal; Eosinophils; Female; Hypersensitivity; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Probucol

Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F2-isoprostanes (F2-IsoPs), free radical-catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoP-M), the major urinary metabolite of the F2-IsoP, 15-F2t-IsoP (8-iso-PGF2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F2-IsoPs in urine and plasma. To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15-F2t-IsoP-M. Analysis of 15-F2t-IsoP-M by GC-NICI-MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine. Urinary excretion of 15-F2t-IsoP-M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8-h period of the study compared to the baseline value (ANOVA, and Student-Newman-Keuls multiple comparisons test). No increase in the urinary excretion of 15-F2t-IsoP-M occurred after inhalation of methacholine. Allergen challenge causes an oxidant injury in human atopic asthmatics. 15-F2t-IsoP-M is a valuable marker of oxidant stress in vivo.

Topics: Allergens; Asthma; Dinoprost; F2-Isoprostanes; Humans; Hypersensitivity; Oxidative Stress

Topics: Antibodies; Antibody Specificity; Aspirin; Asthma; Biomarkers; Chromatography, High Pressure Liquid; Dinoprost; Forced Expiratory Volume; Humans; Hypersensitivity; Immunoenzyme Techniques; Mast Cells; Sensitivity and Specificity

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.

Topics: Adult; Asthma; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Humans; Hypersensitivity; Lysophospholipids; Male; Methacholine Chloride; Prostaglandin D2; Reference Values; Rhinitis; Time Factors

Topics: Chymases; Dinoprost; Histamine Release; Humans; Hypersensitivity; Mast Cells; Nasal Provocation Tests; Prostaglandin D2; Serine Endopeptidases; Time Factors; Tryptases

In asthmatics, both the continuous release of mast cell-derived inflammatory mediators and damage of the airway epithelium may be related to the degree of bronchial responsiveness. We therefore evaluated the effect of inflammatory mediators and mast cell activation on the cholinergic responsiveness of strips of human bronchioles with and without epithelium. Cumulative concentration-response curves to methacholine were generated from strips with or without epithelium before, during and after incubation with threshold doses of either methacholine (3 x 10(-7) M, controls), histamine (3 x 10(-7) M), the thromboxane A2 analogue, U46619 (10(-9) M), prostaglandin (PG) D2 (3 x 10(-7) M), PGF2 alpha (3 x 10(-7) M), leukotriene (LT) C4 (10(-9) M), or anti-human immunoglobulin E (24.4 +/- 4.0 micrograms.ml-1). Strips without epithelium were 1.6 times more sensitive to methacholine than strips with epithelium (-log EC50:5.76 +/- 0.04 vs. 5.97 +/- 0.04, P less than 0.0001). The average contraction in response to identical doses of anti-IgE in strips without epithelium was 3 times greater than the contraction in strips with epithelium (P less than 0.05). Threshold concentrations of histamine, U44619 and PGD2 caused a similar non-parallel leftward shift of the concentration-response curve of strips with or without epithelium to methacholine (P less than 0.05). Together, epithelial denudation and low levels of mediators caused a 4.0- to 9.1-fold increase in sensitivity based on the -log EC10 and a 1.8- to 3.0-fold increase in sensitivity based on the -log EC50.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aged; Aged, 80 and over; Antibodies, Anti-Idiotypic; Dinoprost; Epithelium; Histamine; Humans; Hypersensitivity; Immunoglobulin E; In Vitro Techniques; Inflammation; Kinetics; Lung; Male; Mast Cells; Methacholine Chloride; Middle Aged; Muscle Contraction; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; SRS-A

The ability of arachidonic acid (AA) metabolites to regulate I-region-associated (Ia) antigen expression on macrophages from schistosome-egg-induced pulmonary granulomas was examined. The prostaglandin (PG) analog 15-S-15-CH3-PGE1 (M-PGE1) and PGF2 alpha were found to modulate the kinetics of Ia expression when administered in vivo. Methyl-PGE1 significantly suppressed Ia antigen expression by hypersensitivity granuloma macrophages, while PGF2 alpha appeared to potentiate the expression. Lymphokine-induced Ia antigen expression by cultured granuloma macrophages was likewise dramatically inhibited by M-PGE1. Further analysis using systemically administered inhibitors of AA metabolism demonstrated that the cyclooxygenase inhibitor indomethacin caused augmentation of Ia expression. In contrast, lipoxygenase inhibitors significantly reduced both Ia expression and granuloma size. The role of AA metabolites in modulating chronic inflammation is discussed.

Topics: Alprostadil; Animals; Arachidonic Acids; Cells, Cultured; Dinoprost; Female; Granuloma; Histocompatibility Antigens Class II; Hypersensitivity; Kinetics; Lung Diseases, Parasitic; Lymphokines; Macrophages; Mice; Mice, Inbred CBA; Prostaglandins E, Synthetic; Prostaglandins F; Schistosoma mansoni; Schistosomiasis

The effects of prostaglandins E2 and F2 alpha on renal lesions induced by an anti-rat serum were investigated in rats. It was found that these prostaglandins, administered concomitantly with the antiserum, were able to prevent or remarkably attenuate these lesions. A very interesting finding is that, after prostaglandin administration, no or insignificant morphological alterations of the kidney occurred, in spite of the fact that its mononuclear cell infiltration was somewhat persistent. Hence, in addition to the known effects of these prostaglandins on the immune response components, the blockade of cellular receptors for immunoglobulins is to be considered as a main mechanism in explaining their preventive action in allergic nephritis.

Topics: Animals; Blood Proteins; Dinoprost; Dinoprostone; Female; Hypersensitivity; Immune Sera; Male; Nephritis; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains

The airway effects of adrenergic receptor stimulation/inhibition were investigated in sets of normal (N) and natively ascaris-sensitized (S) beagle dogs. In one group, the effect of beta-adrenergic stimulation/alpha-adrenergic inhibition in airway conductance (Gaw) and dynamic lung compliance (CDYN) were observed. For both N and S dogs, thymoxamine pretreatment served to enhance an isoproterenol inhibition of PGF2 alpha-induced Gaw decreases. No effect was observed in CDYN. In another set of animals, the effects of i.v. administration of norepinephrine (NE), epinephrine (EPI) and phenylephrine (PE), before and after pretreatment with propranolol/indomethacin were observed. For N dogs, all three alpha-adrenergic agents failed to produce bronchospasm; however, propranolol/indomethacin pretreatment significantly potentiated the effects of all three alpha-agents. No significant changes were observed in the CDYN response either prior to or after pretreatment with propranolol/indomethacin. In contrast, for S dogs, all three alpha-agonists produced moderate bronchoconstriction with or without propranolol/indomethacin pretreatment. In addition, the Gaw response to i.v. PE was statistically greater in S dogs than that observed in the N group. Finally, only i.v. PE produced significant decreases in the CDYN response in the S group of animals. These data suggest the presence of alpha-adrenergic influence in the canine airways and elaboration of this action appears to occur best in propranolol/indomethacin-pretreated animals.

Topics: Adrenergic alpha-Agonists; Animals; Ascaris; Dinoprost; Dogs; Female; Hypersensitivity; In Vitro Techniques; Indomethacin; Isoproterenol; Male; Moxisylyte; Muscle Contraction; Prostaglandins F; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Respiratory System