ovalbumin and Dyspnea

The present investigation aimed to evaluate the activity of the essential oil of Mentha arvensis L. on exogenously induced bronchoconstriction in experimental animals. The anti-asthmatic effect of M. arvensis essential oil (MAEO) was studied using histamine aerosol-induced bronchoconstriction in guinea pigs and ovalbumin (OVA) sensitised albino mice. Treatment with M. arvensis oil significantly (p < 0.001) increased the time of preconvulsive dyspnoea in histamine-induced guinea pigs. Oral treatment of MAEO significantly (p < 0.001) decreased absolute eosinophil count, serum level of IgE and the number of eosinophils, neutrophils in BALF. Histopathological examination of lungs showed that essential oil rescinded bronchial asthma. The present investigation provides evidence that MAEO relaxes bronchial smooth muscles and suppressed immunological response to OVA.

Topics: Animals; Asthma; Bronchoconstriction; Disease Models, Animal; Dyspnea; Eosinophils; Female; Guinea Pigs; Histamine; Immunoglobulin E; Lung; Mentha; Mice; Neutrophils; Oils, Volatile; Ovalbumin

Topics: Animals; Antigens; Asthma; Bronchial Hyperreactivity; Cough; Dyspnea; Guinea Pigs; Histamine Antagonists; Inflammation; Male; Ovalbumin; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Respiratory Mucosa

In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.

Topics: Administration, Inhalation; Animals; Antigens; Asthma; Bronchi; Cough; Dyspnea; Guinea Pigs; Lung; Male; Ovalbumin; Relaxin; Respiration

Respiratory viral infections not only exacerbate asthma symptoms but may also be important in the pathogenesis of the disease. We therefore explored the effects of respiratory viral infection on the respiratory response of sensitized guinea pigs to antigen challenge. Lung tissue obtained from uninfected guinea pigs sensitized to ovalbumin aerosol released histamine upon incubation with the antigen in vitro. After antigen challenge in vivo, sensitized animals had significantly greater numbers of eosinophils in their bronchoalveolar lavage fluid than did nonsensitized animals and exhibited airway hyperresponsiveness to methacholine aerosol. When ovalbumin sensitization was initiated 7 days after inoculation with parainfluenza virus type-3 (PI-3), antigen challenge elicited little histamine release from infected lung tissue in vitro. Likewise, subsequent to antigen challenge in vivo, animals failed to exhibit airway hyperresponsiveness or an increased eosinophil population in bronchoalveolar lavage fluid. Similar effects were observed when sensitization was begun 19 days after PI-3 virus inoculation. The mechanism(s) responsible for the attenuated responses to antigen in PI-3 infected animals are unknown but may involve virus-induced effects on immune cells.

Topics: Aerosols; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Count; Disease Models, Animal; Dyspnea; Eosinophils; Guinea Pigs; Histamine Release; In Vitro Techniques; Male; Methacholine Chloride; Ovalbumin; Parainfluenza Virus 3, Human; Paramyxoviridae Infections

A simple, noninvasive, bias-flow ventilated wholebody plethysmographic technique and noninvasive pulmonary analyzer (Buxco dyspnea monitor) were used to quantitate allergic dyspnea in chronically sensitized freely moving guinea pigs. In this study, the effect of azelastine on aeroallergen-induced dyspnea in allergic guinea pigs was investigated. Aeroallergen challenge produced severe dyspnea which was characterized by a 390% increase in the amplitude of pseudo flow signal, a 93% increase in box pressure (delta P) and a 68% decline in relaxation time; these changes signify a tremendous increase in the effort of breathing. The oral administration of azelastine (1 mg/kg) two hours before aeroallergen provocation significantly inhibited allergic dyspnea in this acute allergic asthma model. This technique permits quantitative measurement of the severity of the airway allergic responses in freely moving guinea pigs.

Topics: Aerosols; Allergens; Animals; Asthma; Bronchodilator Agents; Dyspnea; Guinea Pigs; Male; Ovalbumin; Phthalazines; Plethysmography

The pharmacological actions of the new xanthine, isbufylline, were evaluated in several models of airway hyperresponsiveness and airway inflammation in guinea pigs. At a dose (106 mumol kg-1 i.p.) providing complete protection against acetylcholine aerosol-induced dyspnea in the guinea pig, isbufylline inhibited platelet activating factor (PAF)- and antigen-induced eosinophil infiltration into bronchoalveolar lavage fluid 24 h after challenge of normal and actively immunized guinea pigs, respectively. In addition, this dose of isbufylline also inhibited capsaicin-induced extravasation of protein into bronchoalveolar lavage fluid. Isbufylline, 4.2 mumol kg-1 i.v., significantly inhibited PAF-induced bronchial hyper-responsiveness to i.v. histamine, without exerting evident bronchodilator activity. On the other hand the bronchodilator, salbutamol, at a dose (10.4 mumol kg-1 i.p.) shown to be equieffective to isbufylline (106 mumol kg-1 i.p.) for blocking acetylcholine aerosol-induced dyspnea, had no protective action against PAF- or antigen-induced eosinophil recruitment in bronchoalveolar lavage fluid, or against capsaicin-induced plasma protein extravasation. Furthermore, salbutamol (3.5 mumol kg-1) significantly potentiated allergen-induced cell infiltration and PAF-induced bronchial hyperresponsiveness. The results suggest that isbufylline can exert significant anti-inflammatory actions in guinea pig airways, in addition to its bronchodilator activity. These pharmacological activities are not shared by the beta 2-adrenoceptor agonist, salbutamol.

Topics: 1-Methyl-3-isobutylxanthine; Acetylcholine; Albuterol; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Capsaicin; Dextrans; Dyspnea; Fluorescein-5-isothiocyanate; Guinea Pigs; Histamine; Leukocytes; Male; Ovalbumin; Platelet Activating Factor

Guinea pigs were sensitized and boostered with i.p. injections of ovalbumin (OA) 10 micrograms + Al(OH)3 100 mg. Thirteen days after the last injection animals (800-1100 g) were placed in bias flow ventilated whole body plethysmographs and allowed to stabilize for 2 h. Lung function was recorded for up to 2 h before and 5 h after aeroallergen challenge (OA 20 mg/ml, 60 s, 20 psi) by a noninvasive pulmonary analyzer for unrestrained rodents. Aeroallergen challenge produced immediate dyspnea and gasping (peaking between 8 and 17 min). Gasping was associated with an increase in amplitude in the box pressure fluctuations (93%), and in the slope of the fluctuations (391%). Respiratory rate increased (103 to 175 breaths/min, 78%), the product of breathing rate times box pressure amplitude increased (161 to 432, 180%). Relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value) declined (0.16 to 0.05 s, 72%). All of these lung dysfunction changes were highly significant (p < 0.001). Lung dysfunction persisted for 60 to 120 min after challenge. One of 8 animals tested died within 10 min. None of the animals exhibited late asthmatic responses during the 5 h post-challenge period. Based on these data we conclude that this technique allows quantitative analysis of dyspnea, gasping, and an abnormal pattern (waveform) of breathing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bronchial Provocation Tests; Dyspnea; Evaluation Studies as Topic; Guinea Pigs; Hypersensitivity, Immediate; Male; Ovalbumin; Plethysmography, Whole Body; Respiratory Function Tests; Respiratory Hypersensitivity

Aeroallergen-induced dyspnea in guinea pigs was associated with an increase in amplitude in the box pressure fluctuations (212%) and pseudo-flow signal (604%) and an 80% decline (from 0.19 to 0.04 s) in relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value). All of these lung dysfunction changes were highly significant (P < 0.001). Pyrilamine (1 mg/kg, p.o., -2 h) inhibited dyspnea (delta P and delta F) by 50-53%. This technique allows quantitative analysis of allergic dyspnea in conscious, unrestrained guinea pigs.

Topics: Aerosols; Allergens; Animals; Dyspnea; Guinea Pigs; Male; Ovalbumin; Plethysmography, Whole Body; Pyrilamine; Respiratory Function Tests

Acute airway hyperresponsiveness can be induced after exposure to aerosolized ovalbumin in sensitized guinea pigs. The purpose of the present studies was to determine if "pro-inflammatory agents" would potentiate and prolong antigen-induced pulmonary hyperresponsiveness to histamine in guinea pigs. Guinea pigs were sensitized to aerosolized ovalbumin by exposing them to a 3 min aerosol, generated ultrasonically from a 10% ovalbumin solution on day 0 and day 7. On day 13 the guinea pigs were exposed to a 3 min aerosol of deionized water or a pro-inflammatory agent (1 microgram/ml PAF, 1 mg/ml LPS, or 4% B. pertussis vaccine). Twenty-four hours later, on day 14, the conscious guinea pigs were challenged with a 3 min aerosolized ovalbumin exposure (under isoproterenol cover) and the individual guinea pig responsiveness to aerosolized histamine was determined 2 and 24 h later in an anesthetized modified Konzett-Rossler preparation. Under these experimental conditions, ovalbumin challenge to sensitized guinea pigs produced only an acute hyperresponsiveness (about a 3-10-fold shift) to aerosolized histamine, which lasted less than 24 h. The pro-inflammatory agents neither potentiated nor prolonged the duration of the hyperresponsiveness.

Topics: Aerosols; Animals; Dyspnea; Guinea Pigs; Histamine; Inflammation; Lipopolysaccharides; Male; Ovalbumin; Pertussis Vaccine; Respiratory Hypersensitivity

We wanted to study the effect of anti-asthma drugs on antigen-induced dyspnea in conscious Sprague Dawley (S.D.) rats. A line of dyspnea bred rats was produced, where all immunized animals respond with dyspnea when challenged with aerosolized ovalbumin (OA). The animals were immunized intraperitoneally (i.p.) with OA (10 micrograms) together with Al(OH)3 (100 mg) and challenged 2 to 3 weeks later with OA aerosol. We examined the effects of terbutaline (TERB), disodium cromoglycate (DSCG), atropine (ATRO), theophylline (THEO), a 5-HT receptor antagonist methysergide (METH), and two glucocorticosteroids (GCS) budesonide (BUD) and dexamethasone (DEX), on this response. The drugs were given locally either by intratracheal (i.t.) instillation or by aerosol. The rats were placed one by one in an air tight box and the breathing pattern was recorded. Parameters such as time of onset of dyspnea after end of challenge (elapsed time), duration and occurrence of dyspnea, were used to quantify the response. In the vehicle- treated group nearly all animals responded to OA with signs of dyspnea. TERB was the only drug effective when given as an aerosol, whereas when given i.t., also DEX and METH inhibited the dyspnea. Dyspnea is a serious response and can only be alleviated by the most effective anti-asthma drugs.

Topics: Animals; Bronchoconstriction; Bronchodilator Agents; Disease Models, Animal; Dyspnea; Female; Humans; Male; Ovalbumin; Rats; Rats, Inbred Strains

L-663,536 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2, 2-dimethylpropanoic acid) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human polymorphonuclear leukocytes (PMN) (IC50, 2.5 nM). Similarly, L-663,536 inhibited A23187-induced LTB4 formation by rat peripheral blood and elicited PMN. At concentrations where inhibition of leukotriene biosynthesis occurred in human whole blood (1.1 microM), no effect was seen on cyclooxygenase or 12-lipoxygenase, an effect also observed in washed human platelets. The compound had no effect on rat or porcine 5-lipoxygenase indicating that L-663,536 is not a direct 5-lipoxygenase inhibitor. When administered in vivo L-663,536 was a potent inhibitor of antigen-induced dyspnea in inbred rats pretreated with methysergide (ED50, 0.036 mg/kg p.o.) and of Ascaris-induced bronchoconstriction in squirrel monkeys (1 mg/kg p.o.). The compound inhibited leukotriene biosynthesis in vivo in a rat pleurisy model (ED50, 0.2 mg/kg p.o.), an inflamed rat paw model (ED50, 0.8 mg/kg), a model of leukotriene excretion in rat bile following antigen provocation, and a model in the guinea-pig ear where leukotriene synthesis was induced by topical challenge with ionophore A23187 (ED50, 2.5 mg/kg p.o. and 0.6 micrograms topically). The results indicate that L-663,536 is a potent inhibitor of leukotriene biosynthesis both in vitro and in vivo indicating that the compound is suitable for studying the role of leukotrienes in a variety of pathological situations.

Topics: Animals; Arachidonate 5-Lipoxygenase; Bile; Blood Platelets; Dyspnea; Guinea Pigs; Humans; In Vitro Techniques; Indoles; Leukotriene Antagonists; Leukotriene B4; Leukotrienes; Male; Neutrophils; Ovalbumin; Pleura; Rats; Rats, Inbred Strains; Saimiri; Species Specificity; Swine

Sensitized Sprague-Dawley rats developed respiratory impairment after challenge with aerosolized antigen. The response to challenge was heterogeneous. A proportion of each group of rats developed dyspnea and other symptoms similar to asthma; the remainder developed apnea but no other symptoms. Selective breeding from rats which developed dyspnea increased the incidence from 44% in F0 to 55% in F1 and greater than 90% in F2 and F3. Inbreeding also produced a significant increase in the duration of antigen-induced dyspnea. The results from the selective inbreeding suggest antigen-induced dyspnea is controlled genetically, possibly by multiple gene loci. These inbred rats constitute a population which have a predictable response to aerosolized antigen challenge. They should have utility in investigating allergic asthma and evaluating potential new drugs.

Topics: Aerosols; Animals; Antigens; Asthma; Disease Models, Animal; Dyspnea; Female; Immunization; Immunoglobulin E; Male; Ovalbumin; Rats; Rats, Inbred Strains

The preparation of the four isomeric azaxanthones 3 and a number of their aromatic ring substituted derivatives is described. These ketones were converted into the title compounds which were examined for their biological properties. The most interesting compound in this series, the 1-methyl-4-piperidylidene derivative of 1-azaxanthene, shows the profile of an orally effective potent bronchodilating agent as well as a moderate antihistamine. Biological properties of this compound were compared to a number of antihistamines as well as known bronchodilating agents. Structure-activity relationships are also discussed.

Topics: Airway Resistance; Animals; Antigen-Antibody Reactions; Aza Compounds; Bronchodilator Agents; Dyspnea; Guinea Pigs; Histamine H1 Antagonists; Histamine Release; Ileum; In Vitro Techniques; Lung Compliance; Male; Ovalbumin; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Xanthenes

Topics: Amines; Anaphylaxis; Anesthesia, Intravenous; Animals; Blood Pressure; Bronchi; Consciousness; Dyspnea; Female; Histamine H1 Antagonists; Histamine Release; Male; Methysergide; Ovalbumin; p-Methoxy-N-methylphenethylamine; Polymyxins; Pulmonary Circulation; Sheep; Trachea