tranilast and Asthma

Topics: Administration, Inhalation; Administration, Oral; Anti-Allergic Agents; Asthma; Contraindications; Cromolyn Sodium; Cystitis; Dermatitis, Atopic; Digestive System Diseases; Drug Eruptions; Hematologic Diseases; Humans; Kidney Diseases; ortho-Aminobenzoates

Since tranilast, the first inhibitor of chemical mediator (ICMR), had been assessed to be as effective as disodium cromogycate in asthma, several orally active ICMRs, which have no antihistamine or bronchodilator effect, have been developed and prescribed for asthma control in Japan. On the other hand, as histamine H1-antagonists (H1-antagonists) have been shown to inhibit mediator release from mast cells in vitro, these drugs are sometimes classified as ICMR. ICMRs are effective in 40% of asthmatics but it takes 6 or more months for these drugs to improve the symptoms clearly. Although H1-antagonists are effective in only about 30% of asthmatics, they have been shown to be more effective on cough of asthma, cough variant asthma and atopic cough. H1-antagonists have been shown to strongly inhibit alcohol-induced asthma which is evoked in 60% of Japanese asthmatics.

Topics: Asthma; Clinical Trials as Topic; Depression, Chemical; Double-Blind Method; Histamine H1 Antagonists; Humans; Inflammation Mediators; Ketotifen; Mast Cells; ortho-Aminobenzoates; Phthalazines; Terfenadine

Topics: Asthma; Cromolyn Sodium; Drug Hypersensitivity; Flavonoids; Histamine Release; Humans; Hypersensitivity, Delayed; Metyrapone; ortho-Aminobenzoates

Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β. In the current study, we examine the contribution of TGF-β activity to the GC-resistance caused by viral infection. We demonstrate that viral infection of human bronchial epithelial cells with RSV, RV or IAV impairs GC anti-inflammatory action. Poly(I:C), a synthetic analog of double-stranded RNA, also impairs GC activity. Both viral infection and poly(I:C) increase TGF-β expression and activity. Importantly, the GC impairment was attenuated by the selective ALK5 (TGFβRI) inhibitor, SB431542 and prevented by the therapeutic agent, tranilast, which reduced TGF-β activity associated with viral infection. This study shows for the first time that viral-induced glucocorticoid-insensitivity is partially mediated by activation of endogenous TGF-β.

Topics: Anti-Inflammatory Agents; Antiviral Agents; Asthma; Benzamides; Cell Line; Dioxoles; Drug Resistance, Viral; Enzyme Activation; Epithelial Cells; Glucocorticoids; Humans; Influenza A virus; Influenza, Human; ortho-Aminobenzoates; Picornaviridae Infections; Poly I-C; Protein Serine-Threonine Kinases; Pulmonary Disease, Chronic Obstructive; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Rhinovirus; Transforming Growth Factor beta

The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice.. Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done.. Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation.. Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.

Topics: Airway Remodeling; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoalveolar Lavage Fluid; Chronic Disease; Collagen; Disease Models, Animal; Drug Evaluation, Preclinical; Interleukin-13; Leukocyte Count; Lung; Male; Mice; Nitric Oxide; ortho-Aminobenzoates; Transforming Growth Factor beta1

Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder (RP) of TL for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). In the CSD/TL, wet-milled crystalline TL particles with a mean diameter of 122 nm were dispersed, and there was a marked improvement in dissolution behavior of the CSD/TL-RP compared with that of a physical mixture of TL and carrier. Laser diffraction and cascade impactor analyses on the CSD/TL-RP demonstrated high dispersibility and deposition in the respiratory organs with emitted dose and fine particle fraction of ca. 98 and 60%, respectively. Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by histochemical analyses and inflammatory biomarkers such as lactate dehydrogenase, eosinophil peroxidase, and myeloperoxidase. The CSD/TL-RP seemed to be more potent than the physical mixture in inhibiting inflammatory responses, possibly due to the improved dissolution behavior. Systemic exposure of TL after intratracheal administration of CSD/TL-RP at a pharmacologically effective dose (100 μg of TL/rat) was found to be fivefold less than that of the oral TL dosage form at clinical dose (1.67 mg/kg). Given the improved pharmacodynamics and lower systemic TL concentration, the inhalable TL formulation might provide an interesting alternative to oral therapy with a better safety margin for the treatment of asthma and other airway inflammatory diseases.

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Crystallization; Lung; Male; Nanoparticles; ortho-Aminobenzoates; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; Solubility

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.

Topics: Administration, Inhalation; Animals; Anti-Allergic Agents; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Cyclooxygenase 2; Drug Compounding; Drug Stability; Dry Powder Inhalers; Granulocytes; Inflammation Mediators; Lung; Male; Nanoparticles; NF-kappa B; ortho-Aminobenzoates; Ovalbumin; Powders; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; RNA, Messenger

Tranilast has been used in allergic diseases because of its inhibitory effect on mast cells; it also has an anti-fibrotic effect in several diseases. Pentoxifylline (PTX), a methylxanthine derivative, is a potent anti-inflammatory drug that is known to manifest its effect through the inhibition of Th1 cytokine, but with an uncertain effect on Th2 cytokine. Seven-week-old female BALB/c mice were studied as a chronic asthma model. The mice were challenged with house dust mite (HDM) antigen for 7 weeks. Each group of mice was given an intraperitoneal injection of tranilast, PTX, or tranilast plus PTX before antigen administration. In this mouse model of chronic asthma, tranilast, and PTX each had an inhibitory effect on airway remodeling as well as on airway hyperresponsiveness (AHR) and airway inflammation. The improved events of these drugs were related with the inhibition of the Th2 cytokine IL-13 and TGF-beta 1. Immunohistochemical analysis showed that decreases in the peribronchial trichrome stained area in each treatment group were associated with improvements in the peribronchial smooth muscle hyperplasia, collagen type I, and collagen type III deposition. These drugs could have potential beneficial effects on chronic asthma, especially with respect to airway remodeling.

Topics: Animals; Anti-Allergic Agents; Antigens, Dermatophagoides; Asthma; Bronchial Hyperreactivity; Bronchioles; Bronchoalveolar Lavage Fluid; Cell Count; Drug Therapy, Combination; Eosinophils; Female; Fibrillar Collagens; Goblet Cells; Hyperplasia; Immunoglobulin E; Interleukin-13; Leukocytes; Mice; Mice, Inbred BALB C; Muscle, Smooth; ortho-Aminobenzoates; Pentoxifylline; Pulmonary Fibrosis; Specific Pathogen-Free Organisms; Transforming Growth Factor beta1

Cell suspension cultures of Luffa cylindrica, Citrullus lanatus, and related cucurbitaceous plants accumulate large quantities of bryonolic acid (3 beta-hydroxy-D:C-friedoolean-8-en-29-oic acid) [1], an acidic, pentacyclic triterpene found exclusively in the roots of the intact plants. This compound could readily be isolated from cultured cells with CHCl3 and purified simply by recrystallization. Pharmacological tests using mice demonstrated that bryonolic acid or its derivative is active against at least three types of allergies and that its activity could be increased significantly by preparing synthetic derivatives, in particular a potassium salt of its succinate ester. The biosynthesis of bryonolic acid from mevalonic acid via isomultiflorenol has been elucidated by tracer and enzymological experiments using cultured cells of watermelon both in vitro and in vivo. Furthermore, cell fractionation and electron microscopic studies on subcellular structures of luffa cells suggested that minute vesicles originating from elongated, rough endoplasmic reticulum probably play an important role in the transport of bryonolic acid which largely accumulates in the cell wall of cultured cells. The results obtained from the present study indicate that plant cell culture would be useful not only as a biological system for elucidating biosynthetic mechanisms but also as a potential source of new pharmacologically active compounds.

Topics: Animals; Arthus Reaction; Asthma; Dermatitis; Erythrocytes; Hypersensitivity; Male; Mice; Mice, Inbred Strains; Passive Cutaneous Anaphylaxis; Plants; Triterpenes

We tested the effect of Tranilast [N-(3',4'-dimethoxycinnamoyl anthranilic acid)], one of the anti-allergic agents, on the induction of interleukin 2 (IL2) responsiveness of lymphocytes from patients with bronchial asthma or hen-egg allergy following stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA), respectively. Mononuclear cells pretreated with Tranilast for 12 h failed to respond to IL2 following incubation with Df or OVA. Also Tranilast inhibited purified protein derivative (PPD)-induced IL2 responsiveness of normal lymphocytes but not the Con A-induced IL2 responsiveness of normal or allergen-sensitized lymphocytes. These results suggested that Tranilast has some immunosuppressive effect in that it inhibits antigen-induced IL2 responsiveness. Separation of potential target cells of Tranilast disclosed that antigen-presenting adherent cells were more susceptible to Tranilast than IL2-responding T-cell rich populations. Expression of HLA-DR and -DQ antigens but not DP antigens on macrophages, was significantly suppressed by treatment with Tranilast, although Tranilast scarcely decreased HLA class II antigens expression on B-cells. The suppression was overcome by interferon-gamma, which was known as an inducer for class II antigen expression. Taken together, Tranilast may suppress antigen-induced IL2 responsiveness by inhibiting HLA-DR and HLA-DQ antigens on macrophages.

Topics: Adult; Animals; Antigens, Dermatophagoides; Asthma; Child, Preschool; Food Hypersensitivity; Glycoproteins; Histamine H1 Antagonists; HLA-D Antigens; Humans; In Vitro Techniques; Infant; Interleukin-2; Lymphocytes; Macrophages; Mites; ortho-Aminobenzoates; Ovalbumin

We report 2 cases of eosinophilic cystitis induced by Tranilast, which was used for the treatment of bronchial asthma. In case 2 Tranilast itself and its metabolic derivative proved to be inciting agents by a drug-induced lymphocyte stimulation test. The literature on this association is reviewed.

Topics: Aged; Asthma; Cystitis; Eosinophilia; Female; Histamine H1 Antagonists; Humans; Male; ortho-Aminobenzoates

Topics: Asthma; Cromolyn Sodium; Histamine Antagonists; Humans; Ketotifen; ortho-Aminobenzoates; Phthalazines; Platelet Activating Factor; SRS-A

The effect of antiallergic agents with no antihistamine activity on bronchial hypersensitivity to histamine inhalation was studied in 37 asthmatic patients. Improvement in bronchial hypersensitivity to histamine was observed in 11 out of the 24 (46 percent) antiallergic agents-treated patients, but in none of the 13 (0 percent) untreated patients. The 11 patients whose bronchial hypersensitivity improved with antiallergic agents consisted of eight short-term cases of less than one year's duration and three long-term cases of more than one year's duration. Thus, improvement in bronchial hypersensitivity was observed in 8 of 11 (73 percent) short-term cases, and 3 of 13 (23 percent) long-term cases. A significant improvement in %FEV1 was observed only in the short-term cases treated with antiallergic agents, but the improvement of baseline FEV1 did not seem to explain entirely the improvement in bronchial hypersensitivity seen. The decrease in bronchial hypersensitivity was in parallel with that of other asthmatic symptoms. These results suggest that antiallergic agents might be most effective in the treatment of asthmatic patients with a short-term disease duration.

Topics: Adult; Aged; Asthma; Bronchial Provocation Tests; Cromolyn Sodium; Female; Forced Expiratory Volume; Histamine; Histamine Antagonists; Humans; Male; Middle Aged; ortho-Aminobenzoates; Quinolones

Topics: Asthma; Chemotactic Factors, Eosinophil; Cromolyn Sodium; Cytokines; Depression, Chemical; Histamine; Humans; Hypersensitivity; Ketotifen; Mast Cells; ortho-Aminobenzoates; Phthalazines; SRS-A

A 38-year-old man with asthma developed eosinophilic polymyositis following the administration of Tranilast, an antiasthmatic agent. Low grade fever, erythematous rashes on the entire body, dysphagia, blood eosinophilia, elevations of serum creatine phosphokinase and myoglobin levels, and inverted T waves in the electrocardiogram were noted. A muscle biopsy showed focal degeneration of muscle fibers with an infiltrate of eosinophils and lymphocytes. A rechallenge with Tranilast resulted in erythema formation, blood eosinophilia, and elevations of some serum muscle enzymes and myoglobin levels. Tranilast was considered to be the causative agent. This is the first reported case of Tranilast-induced eosinophilic polymyositis.

Topics: Asthma; Drug Eruptions; Eosinophilia; Humans; Male; Middle Aged; Myositis; ortho-Aminobenzoates

Blood eosinophils obtained from 25 patients with bronchial asthma were reacted with anti-IgG or with normal rabbit serum as the control. Morphological changes were examined by light microscopy, scanning electron microscopy and transmission electron microscopy. Reactive eosinophils in morphology with anti-IgG (27.8 per cent) were significantly higher (p less than 0.001) than those with the control (1.2 per cent). We also examined the effects of ketotifen and tranilast, both of which have eosinophil chemotactic inhibitory functions, on the morphological changes. Ketotifen altered the morphological reactivation of eosinophils and the generation of leukotrienes induced by anti-IgG, and this inhibition occurred in a concentration-dependent manner. Tranilast had no effect on the morphology of eosinophils and the generation of leukotrienes. These results suggest that eosinophil IgG receptors may have a role in the pathogenesis of asthma and that ketotifen may prevent their reactivity and, thus, could be of potential use in the treatment of asthma.

Topics: Adolescent; Adult; Antibodies, Anti-Idiotypic; Asthma; Eosinophils; Humans; Immunoglobulin G; Ketotifen; Middle Aged; ortho-Aminobenzoates; Receptors, Immunologic

We treated bronchial asthma patients with anti-allergic agents for more than three months, and examined their effects on the airway hyperreactivity in 15 cases; five were short cases (disease duration was less than one year from the onset) and 10 were long cases (disease duration was more than one year). A significant improvement in airway hyperreactivity to histamine inhalation was observed in all five short cases. In 4 out of 5 short cases, the threshold of histamine concentration reached to the normal level of 10,000 micrograms/ml. On the other hand, the significant improvement was observed only in 2 out of 10 cases. We suggested that in "short asthma cases" the airway hyperreactivity could improve with the use of anti-allergic agents in a relatively short period and at a high rate.

Topics: Adult; Asthma; Bronchi; Cromolyn Sodium; Drug Therapy, Combination; Female; Histamine; Humans; Ketotifen; Male; Middle Aged; ortho-Aminobenzoates; Phthalazines; Time Factors

We investigated the difference in the influence on 10 allergic factors of 3 anti-allergic drugs: azelastine, tranilast, ketotifen. We determined the ranking of 10 allergic factors using the relative range ratio calculated by Multiple factor analysis. The ranking as follows: (1) Eosinophil count (2) IgE RAST score to H.D. (3) IgG4 antibody titers to egg white (4) IgE RAST score to egg white (5) IgE RAST score to D.f. (6) IgG4 antibody titers to milk (7) IgE RIST (8) IgG4 antibody titers to soybean (9) IgE RAST score to soybean (10) IgE RAST score to milk. Then we split 122 asthmatic children (mean age: 9.3) into 3 groups and gave each group a different one of the 3 anti-allergic drugs for one year. From daily records of asthma attacks and clinical findings, we classified the children into improved and not-improved groups within their respective anti-allergic drug group, and we investigated the changes in and the change ratios of the 10 allergic factors by the Student t method over this one year. The results were as follows. 1) There was no difference in the chang of 3 allergic factors (Eosinophil count, IgG4 antibody titers to egg white and IgE RIST) among the 3 anti-allergic drug treated groups. 2) The specific IgE antibodies to H.D. and D.f. had a remarkable decline tendency in treated groups by azelastine and tranilast. 3) The specific IgE antibody to egg white had a remarkable decline tendency in treated group by ketotifen.

Topics: Adolescent; Asthma; Child; Child, Preschool; Eosinophils; Female; Histamine H1 Antagonists; Humans; Immunoglobulin G; Ketotifen; Leukocyte Count; Male; Multivariate Analysis; ortho-Aminobenzoates; Phthalazines; Prognosis; Pyridazines; Radioallergosorbent Test

Topics: Allergens; Animals; Asthma; Child, Preschool; Epitopes; Humans; Infant; Interleukin-2; Lymphocyte Activation; Mites; ortho-Aminobenzoates

Effects of antiallergic agents on 2,4-dinitrophenylated Ascaris extract (DNP-As)-induced bronchial asthma were studied in Lewis rats, and compared with those on passive cutaneous anaphylaxis (PCA). Effects of methysergide and chlorpheniramine on the bronchial asthma model were also investigated. Rats were actively sensitized with DNP-As antigen and with killed Bordetella pertussis. After 8 d, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As caused a marked asthmatic bronchoconstriction without significant effect on systemic blood pressure and heart rate. Disodium cromoglycate (DSCG), 10 mg/kg, i.v., trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) and tranilast at doses of 30 and 100 mg/kg, intraduodenally, significantly inhibited the asthmatic response. Chlorpheniramine and methysergide at a dose of 1 mg/kg, i.v. also significantly inhibited it. The above doses of NCO-650 and tranilast significantly inhibited 48 h PCA, while DSCG almost abolished the PCA. These results indicate that 1) NCO-650 and tranilast inhibited both the asthmatic response and PCA in almost the same degree, 2) DSCG inhibited PCA much more strongly than asthmatic response, and 3) histamine and 5-hydroxytryptamine may be involved in this asthmatic response.

Topics: Anaphylaxis; Animals; Asthma; Chlorpheniramine; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Disease Models, Animal; Histamine H1 Antagonists; Methysergide; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Lew; Ventilation-Perfusion Ratio

We encountered 8 cases of cystitis probably caused by Tranilast. Bladder biopsy performed on 6 of the 8 cases revealed eosinophilic cystitis in 3 cases. In the lymphocyte stimulation test using Tranilast as an antigen, a positive and false positive reaction was seen in one case each. This disease seemed to occur as a result of allergy of the bladder specific to Tranilast.

Topics: Adult; Aged; Asthma; Cystitis; Eosinophilia; Female; Humans; Lymphocyte Activation; Male; Middle Aged; ortho-Aminobenzoates

Topics: Asthma; Child; Child, Preschool; Desensitization, Immunologic; Factor Analysis, Statistical; Female; Humans; Ketotifen; Male; ortho-Aminobenzoates; Prognosis

Topics: Adolescent; Adult; Animals; Asthma; Child; Female; Guinea Pigs; Histamine; Humans; Male; Middle Aged; ortho-Aminobenzoates; SRS-A

Topics: Adult; Aged; Asthma; Cromolyn Sodium; Female; Humans; Ketotifen; Male; Middle Aged; ortho-Aminobenzoates; Phthalazines; Terbutaline; Theophylline

Antiallergic asthma effect of trans-4-guanidinomethylcyclohexane-carboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650), a new anti-allergic drug, was investigated in comparison with those of tranilast and disodium cromoglycate (DSCG) in anesthetized dogs. The asthmatic bronchoconstriction was induced by inhalation of Ascaris suum antigen (Asc-Ag) to naturally Ascaris-sensitive dogs. The airway resistance was determined using the modified Konzett-Rössler method. Both intravenous (1 and 5 mg/kg) and intraduodenal (10, 30 and 100 mg/kg) administrations of NCO-650 prior to the antigen challenge markedly inhibited the asthmatic bronchoconstriction induced by Asc-Ag inhalation. The antiasthmatic effect of NCO-650 was much stronger than that of DSCG (10 mg/kg, i.v.) and was about three-fold stronger than that of tranilast. On the other hand, when NCO-650 was administered after the antigen challenge, the agent had no inhibitory effect on the Asc-Ag induced bronchoconstriction. As for the effects on increased airway secretion at the time of asthmatic attack, NCO-650 inhibited the excessive secretions without any remarkable change in the viscosity of the secretions. NCO-650 had no effect on the bronchoconstriction induced by inhalation of acetylcholine, suggesting that NCO-650 appears to have no anti-cholinergic effect and thus no effect on the vagal reflex that occurred during the asthmatic responses. The above findings show that NCO-650 may be useful for the treatment of bronchial asthma as an orally active drug.

Topics: Acetylcholine; Animals; Antigens, Helminth; Ascaris; Asthma; Bronchi; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Dogs; Hypersensitivity, Immediate; Male; ortho-Aminobenzoates; Protease Inhibitors; Skin Tests

Development of a nonimmunologically induced experimental asthma model using compound 48/80 was attempted. Male mongrel dogs anesthetized with pentobarbital-Na were immobilized with decamethonium bromide under artificial respiration. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of compound 48/80 caused no change in VO even in high concentrations up to a 1% solution. Infusion of compound 48/80 into the bronchial artery at a dose of 0.2 mg/min for 10 min by using the right bronchial perfusion method caused a marked increase in VO accompanied by decreases in perfusion pressure and systemic blood pressure. The compound 48/80-induced bronchoconstriction was inhibited 58% by surgical vagotomy and was almost abolished by chlorpheniramine (10 mg/kg, intraduodenally (i.d.)). Disodium cromoglycate (inhalation of 1% solution along with 5 mg/kg, i.v.), tranilast (300 mg/kg, i.d.) and NCO-650, a new antiallergic drug (100 mg/kg, i.d.) significantly inhibited the compound 48/80-induced bronchoconstriction. These results indicate that compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, the main chemical mediator involved in this response would be histamine acting through H1-receptors, and effects of mast cell stabilizers can be evaluated with this model.

Topics: Airway Resistance; Animals; Asthma; Blood Pressure; Chlorpheniramine; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Disease Models, Animal; Dogs; Histamine; Histamine H1 Antagonists; Male; Mast Cells; ortho-Aminobenzoates; p-Methoxy-N-methylphenethylamine; Vagotomy

Topics: Administration, Inhalation; Administration, Oral; Animals; Asthma; Child, Preschool; Cromolyn Sodium; Guinea Pigs; Histamine H1 Antagonists; Humans; Ketotifen; ortho-Aminobenzoates; Phthalazines; Piperazines; Rats

Topics: Asthma; Depression, Chemical; Histamine Release; Humans; In Vitro Techniques; Leukocytes; Lung; ortho-Aminobenzoates; SRS-A

The cytomorphologic features of voided urine specimens from two patients with antiallergic drug (Tranilast)-induced eosinophilic cystitis are described. The urothelial cells tend to occur in clusters and are of variable size. The remarkable vacuolization is observed in the cytoplasm. The markedly vacuolated cytoplasm which may be infiltrated by polymorpho-nuclear leucocytes is unremarkable. Some nuclei usually show transparent center surrounded by a rim of chromatin. The nucleoli are prominent. Marked vacuoles in the nucleus is observed. These findings are very important cytomorphologic characteristics for differential diagnosis between eosinophilic cystitis and malignant bladder tumor and cystitis due to bacterial infection.

Topics: Aged; Asthma; Cystitis; Diagnosis, Differential; Eosinophils; Female; Humans; Male; Middle Aged; ortho-Aminobenzoates; Urinary Bladder Neoplasms; Urine

The effects of 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), a new antiallergic drug, on both bronchial asthma and active cutaneous anaphylaxis (ACA) reaction induced by Ascaris suum antigen in dogs were investigated. The airway resistance was determined using the modified Konzett-Rössler method. Sm 857 in doses of 30 and 100 mg/kg intraduodenally (i.d.) produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris antigen in naturally sensitized dogs. Intravenous administration of Sm 857 (10 mg/kg) also strongly inhibited the Ascaris-induced bronchial asthma. Sm 857 had a more powerful antiasthmatic activity than tranilast. In ACA reactions, 10 dilutions of Ascaris extract and histamine were injected intradermally to dogs and each wheal provoked was determined. Sm 857 (100 and 300 mg/kg i.d.) had little or no inhibitory effect on the antigen-induced wheals, while tranilast only in a high dose (300 mg/kg i.d.) showed an inhibitory effect. Chlorpheniramine (10 mg/kg i.d.) prevented the ACA reaction completely. Sm 857 thus appeared to have no antihistaminic effect. Above findings suggest that Sm 857 may be useful for the treatment of bronchial asthma as an orally active drug, exerting its action probably through a mast cell stabilizing effect.

Topics: Animals; Antigens, Helminth; Ascaris; Asthma; Bronchi; Dogs; Dose-Response Relationship, Drug; Hypersensitivity; Immunization; Male; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Quinazolines; Respiration

First, the cases of two patients with intractable cystitis are presented. The first case was a 72-year old man who was admitted to our clinic with bladder symptoms (pollakisuria, pain on urination, hematuria and so forth) for about one month. These symptoms were not relieved by several kinds of antibiotic therapy. For the previous three months he had been suffering from asthma bronchiale. Rizaben (tranilast) was administered for more than two months. An excretory urogram showed normal renal function, but a small bladder with trabeculation. Voiding cystourethrograms revealed bilateral VUR. Cystoscopy disclosed remarkable red areas in the bladder mucosa. A bladder biopsy was done and the pathological finding was cystitis chronica. Intravesical installation of AgNO3, steroid administration, anti-histamic and anti-allergic therapy did not resolve these symptoms. However, Chinese medicines (Chorêto and Ryutanshakantõ) were effective. The second case was a 39-year old woman who visited our clinic complaining of bladder symptoms with hematuria for more than two months. In the past, she had suffered from asthma bronchiale. Rizaben (tranilast) was administered for three months. On cystoscopic examination, a small amount of intravesical coagula and erythematous, edematous areas with petechiae, were observed. The intravesical installation of AgNO3, anti-histamic and antiallergic therapy and gamma-globulin were not effective, but Chinese medicine was effective. Two other cases of cystitis due to Rizaben are presented briefly. Including our cases, 24 cases of cystitis chronica or eosimophilic cystitis due to Rizaben have been reported recently.

Topics: Adult; Aged; Asthma; Cystitis; Female; Humans; Male; ortho-Aminobenzoates; Urinary Bladder

Topics: Aerosols; Animals; Antigens; Asthma; Bronchial Provocation Tests; Guinea Pigs; Injections, Intravenous; Male; ortho-Aminobenzoates; Ovalbumin; SRS-A