UMLS:C0155339 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
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An animal disease model of allergic rhinitis was developed with Brown Norway (BN) rat, a high immunoglobulin E responder strain. BN rats were immunized with ovalbumin (OA) and made to suffer from allergic rhinitis. The severity of allergic rhinitis was assessed by determining the extent of the three kinds of markers, Evan's blue, histamine and N-acetyl-beta-D-glucosaminidase, released into the nasal perfusate following the OA challenge to the nasal cavity of OA-sensitized BN rats. This experimental system was appreciated by antiallergic drugs; chlorpheniramine maleate inhibited the release of Evan's blue and elevated that of histamine, but did not affect the N-acetyl-beta-D-glucosaminidase level. Halopredone acetate inhibited the releases of all the three markers. The estimation of the released markers using allergic rhinitis brought about in BN rats was found to be a useful experimental system for evaluating the effect of drugs on allergic rhinitis.
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PMID:Allergic rhinitis model with Brown Norway rat and evaluation of antiallergic drugs. 170 88

Platelet-activating factor (PAF) may be an important mediator of allergic rhinitis. In the present study we evaluated the effectiveness of a recently described PAF antagonist (ABT-491) in rat and guinea pig models of allergic rhinitis. PAF, when perfused through the nasal passages of anesthetized Brown Norway rats, provoked an acute increase, measured as dye leakage, in nasal vascular permeability evident within 15 min after exposure to PAF. ABT-491, given orally 1 hr before PAF challenge, inhibited the response in a dose-related manner (ED50 = 0.3 mg/kg). Intranasal perfusion with ovalbumin in rats sensitized to the antigen 18 to 21 days before challenge also induced an increase in vascular permeability. The antigen-induced leakage was inhibited a maximum of 74% (P < or = .001) by pretreatment with ABT-491 (3 mg/kg p.o.). An antihistamine (mepyramine, 10 mg/kg i.p.), a serotonin antagonist (methysergide) and a 5-lipoxygenase inhibitor (A-79175) also exhibited efficacy in this model (56%, 87% and 65% inhibition, respectively). Nearly complete inhibition (93%, P < or = .001) of the response was achieved by coadministration of ABT-491 and methysergide. In guinea pigs intranasal administration of PAF resulted in increased airway resistance that was inhibited in a dose-dependent manner by oral administration of ABT-491 (ED50 = 1 mg/kg). Antigen-induced nasal airway resistance, triggered by exposure of sensitized animals to aerosolized ovalbumin, was also inhibited by ABT-491 (maximum inhibition 64%, P < or = .05, 10 mg/kg p.o.). The effectiveness of the antagonist was increased to 80% protection by coadministration with either an antihistamine or a 5-lipoxygenase inhibitor, agents which were separately insignificant in blocking the response to antigen. These results suggest a therapeutic utility for ABT-491, perhaps in combination with other anti-inflammatory agents, in the treatment of allergic rhinitis.
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PMID:The role of platelet-activating factor (PAF) and the efficacy of ABT-491, a highly potent and selective PAF antagonist, in experimental allergic rhinitis. 943 64

The purpose of this study is to examine the co-existence of asthma and allergic rhinitis among former college students who were diagnosed with these diseases either before or after their freshman year. A total of 738 former Brown University students (69% males and 31% females) who were evaluated and underwent skin testing during their freshman year completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma. The mean age of the participants at the time of the follow-up study was 40 years. In this group, the cumulative incidence of asthma was 11.3% (84/738), hay fever was 41.5% (306/738), and nonseasonal allergic rhinitis was 14.0% (103/738). The cumulative incidence of allergic rhinitis (hay fever) and/or nonseasonal allergic rhinitis (was 45.8% (338/738). Among the 84 individuals with a cumulative incidence of asthma, 63 (75.0%) had a history of hay fever, 27 (32.1%) had a history of nonseasonal allergic rhinitis, and 72 (85.7%) had a history of allergic rhinitis. Among the 306 participants with a cumulative incidence of hay fever, 63 (20.6%) had a history of asthma. Twenty-seven (26.2%) of the 103 individuals with a history of nonseasonal allergic rhinitis had a cumulative incidence of asthma. Among the 338 individuals with a cumulative incidence of allergic rhinitis 72 (21.3%) had a history of asthma. Among the participants with a history of both asthma and hay fever, 44.8% developed hay fever first, 34.5% developed asthma first, and 20.7% developed both diseases at the same time. Among the individuals with a history of asthma and nonseasonal allergic rhinitis, 38.5% developed nonseasonal allergic rhinitis first, 30.8% developed asthma first, and 30.8% developed both diseases at the same time. This study further demonstrates the frequent co-existence of asthma and allergic rhinitis. Among asthmatics, allergic rhinitis occurred in 85.7%. Only 14.3% of asthmatics did not have allergic rhinitis. Among individuals with allergic rhinitis, asthma occurred in 21.3%. Also, allergic rhinitis often precedes or occurs at the same time as asthma.
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PMID:Co-existence of asthma and allergic rhinitis: a 23-year follow-up study of college students. 972 49

The purpose of this study is to examine the natural history of hay fever among former college students who were diagnosed with this disease either before or after their freshman year. The diagnosis of hay fever or seasonal allergic rhinitis was based on a history of watery, itchy eyes, rhinorrhea, and sneezing occurring for at least 2 consecutive years during the same seasonal period. A total of 738 former Brown University students (69% males and 31% females) who were evaluated and underwent skin testing during their freshman year completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma. The mean age of this group at the time of the follow-up study was 40 years. During the 23 years subsequent to the original study, 131 developed new hay fever in addition to the 175 who had hay fever as college freshman, totaling 306. At the time of the 23-year follow-up, improvement was noted by 84.8% (28/33) of those with hay fever onset 1-5 years, 63.6% (56/88) of those with onset 6-12 years, 55.6% (40/72) of those with onset 13-19 years, and 38.7% (41/106) of those with onset 20 years and older. Among those with an unknown age of onset, 42.9% (3/7) reported improvement of hay fever symptoms. The trend of increasing percentage of improvement with younger age of onset of hay fever is of statistical significance (p value of < 0.0001) using the chi-squared test for trend. A total of 54.9% (168/306) had noted improvement, of which 22.9% (70/306) reported being symptom free and 32.0% (98/306) reported being better but not symptom free. Of the remaining 45.1% (138/306), the hay fever was unchanged in 33.3% (102/306), worsened in 9.2% (28/306), and unknown in 2.6% (8/306). This study suggests that over a long period of time, hay fever symptoms will improve in the majority of individuals.
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PMID:Natural history of hay fever: a 23-year follow-up of college students. 980 40

During the last decades, the prevalence of allergy has increased worldwide. Allergic rhinitis ("hay fever") and asthma are two of the most common allergic diseases. A possible cause for increased allergy to pollen is air pollution. The increase of industrialization and the number of diesel engines associated with diesel exhaust particles (DEP) in the air parallel the increase in allergic airway diseases. To investigate the adjuvant effect of DEP in pollen allergy, Brown Norway (BN) rats were sensitized intranasally or intratracheally with timothy grass pollen (Phleum pratense) with or without DEP (3 mg/ml). Intranasal sensitization (200 microl, 10 mg/ml) was performed daily for 5 consecutive days and intratracheal sensitization (200 microl, 10 mg/ml) was performed once. Challenge with pollen was performed at day 21 similarly to the sensitization protocol. Blood samples were taken at day 28 after the first sensitization. The binding of DEP to pollen grains was studied by scanning electron microscopy and the inflammatory response in the lung was studied by light microscopy. Immunoglobulin E (IgE) and IgG(1) responses against pollen grains were measured by digoxigenin (DIG) enzyme-linked immunosorbent assay (ELISA). Scanning electron microscopy revealed a mixture of free DEP and DEP associated with pollen grains. Both intranasal and intratracheal routes of administration of pollen grains induced inflammatory reactions in the lung with an influx of macrophages, eosinophilic granulocytes, and granuloma formation. Pollen grains were localized in the alveoli after both intranasal and intratracheal administration and were surrounded by macrophages. The number and localization of pollen grains were similar for both routes of administration. After coexposure with DEP, DEP-loaded macrophages were found around the pollen. Localization, inflammatory reaction, and integrity of pollen were similar to those seen without DEP. At day 28, specific IgE and IgG(1) antibodies were found in serum of rats immunized intranasally or intratracheally. IgE antibody response was higher in rats immunized with pollen grains and DEP than in rats immunized with pollen only (dilution mean +/- SEM: 59.4 +/- 4.6 vs. 27 +/- 5.1). The IgG(1) antibody response was much higher compared to the IgE response (factor of 10(4)), but the level of IgG(1) antibodies was only slightly increased by DEP (dilution mean +/- SEM: 24.2 +/- 2.0 x 10(4) vs. 16.1 +/- 2.1 x 10(4)). In conclusion, the intranasal application of pollen in the BN rat is a suitable and elegant method to evoke inflammatory reactions in the lung and pollen-specific IgE responses measured by DIG ELISA. Finally, this model gives similar results on adjuvant activity of DEP found in the ovalbumin models presented previously.
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PMID:A pollen model in the rat for testing adjuvant activity of air pollution components. 1056 99

The effect of a newly synthesized compound, HSR-609, on rat experimental rhinitis was investigated. In the first part of the study, a new experimental nasal allergic late phase eosinophilia model in Brown Norway (BN) rats was investigated. The increase in the number of antigen inhalations resulted in the proportional increase in the number of inflammatory cells such as macrophages, eosinophils and neutrophils in the nasal cavity lavage fluid (NCLF) at 5 h after each inhalation. The number of inflammatory cells reached a maximum 8 h after the antigen perfusion. Submaximum response was observed at 5 h after the antigen provocation. In this system, the serum IgG and IgE antibody titers measured by homologous passive cutaneous anaphylaxis were 160 and 640, respectively. In the second part of the study, the effects of prednisolone, cetirizine and a newly synthesized amphoteric antiallergic agent, HSR-609, on this allergic late nasal eosinophilia and neutrophilia in BN rats were investigated. Prednisolone and HSR-609 significantly inhibited the increase in the number of eosinophils in the NCLF but not cetirizine. Furthermore, prednisolone showed the inhibition of the increase in the number of macrophages and neutrophils in NCLF. These results suggest that this late phase eosinophilia model in the nose of BN rats may be useful for investigating the therapeutic drugs for nasal allergy and a newly synthesized amphoteric antiallergic agent, HSR-609, may be useful for the treatment of allergic rhinitis with eosinophilia.
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PMID:Effects of an amphoteric antiallergic agent, HSR-609, on antigen-induced late phase nasal eosinophilia in brown Norway rats. 1109 74

The purpose of this study is to examine the relationship between the course of asthma and allergic rhinitis among former Brown University students who were diagnosed with these diseases either before or after their freshman year of 1962 or 1963. A total of 738 former students, who were evaluated and underwent skin testing during their freshman year, completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma and are the focus of this study. The activity of asthma as related to the course of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis) was examined. Among 44 asthmatic subjects with purely seasonal allergic rhinitis (hay fever and no history of nonseasonal allergic rhinitis), asthma was active in 75% of those with worse hay fever, 70% of those with unchanged hay fever, 50% of those with better (but not symptom-free) hay fever, and 10% of those with symptom-free hay fever. The resolution of asthma symptoms correlated significantly with improvement in hay fever (p = 0.0053). Among 70 asthmatics with any form of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis), asthma was active in 75.0% of those with worse allergic rhinitis, 66.7% of those with unchanged allergic rhinitis, 53.3% of those with better (but not symptom-free) allergic rhinitis, and 20.0% of those with symptom-free allergic rhinitis. The resolution of asthma symptoms correlated significantly with improvement in allergic rhinitis (p = 0.0052). The activity of allergic rhinitis as related to the course of asthma was also examined. Among 44 asthmatic subjects with purely seasonal allergic rhinitis (hay fever and no history of nonseasonal allergic rhinitis), hay fever was active in 100% of those with worse asthma, 100% of those with unchanged asthma, 90.9% of those with better (but not symptom-free) asthma, and 60.9% of those with symptom-free asthma. The resolution of hay fever symptoms correlated significantly with improvement in asthma (p = 0.0109). Among 71 asthmatic subjects with any form of allergic rhinitis (hay fever and/or nonseasonal allergic rhinitis), allergic rhinitis was active in 91.9% of those with active asthma and 64.7% of those with symptom-free asthma. The resolution of allergic rhinitis symptoms correlated significantly with improvement in asthma (p = 0.0078). In summary, among individuals with asthma and allergic rhinitis, improvement of allergic rhinitis was associated with a resolution of asthma symptoms, whereas a worsening of allergic rhinitis was associated with the persistence of asthma symptoms. Likewise, among asthmatic subjects with allergic rhinitis, improvement of asthma was associated with a resolution of allergic rhinitis symptoms, whereas a worsening of asthma was associated with the persistence of allergic rhinitis symptoms.
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PMID:The course of asthma parallels that of allergic rhinitis: a 23-year follow-up study of college students. 1119 Nov 4

Repeated exposures to ozone cause inflammation and mucous cell metaplasia (MCM) in the nasal mucosa of laboratory animals. Similar cellular responses occur in humans during allergic rhinitis. We tested the hypothesis that exposure to ozone will enhance the inflammatory and epithelial responses associated with allergic rhinitis. Ovalbumin (OVA)-sensitized Brown Norway rats were exposed to ozone (0.5 ppm, 8 h/day) for 1 day or 3 consecutive days. Immediately after each ozone exposure, animals were challenged intranasally (IN) with either sterile saline or OVA dissolved in saline (1%, 50 microg/nasal passage). Twenty-four h after the last IN challenge rats were sacrificed; nasal tissues were removed and processed for light microscopic examination and morphometric analysis of numeric densities of inflammatory and epithelial cell populations and volume densities of intraepithelial mucosubstances. A single OVA challenge caused a significant influx of neutrophils and eosinophils into the submucosa of all nasal tissues. Ozone exposure further enhanced the appearance of eosinophils in the maxilloturbinates of OVA-challenged rats but did not increase inflammation in other nasal tissues. After 3 days of ozone/OVA coexposures, the nasal transitional epithelium lining the maxilloturbinates had increased numbers of epithelial cells as well as the appearance of mucus-containing cells in areas normally absent of these secretory cells (i.e., MCM). Multiple challenges with OVA caused increased epithelial mucosubstances in the respiratory epithelium lining the septum without increasing the number of epithelial cells. Multiple exposures to both ozone and OVA caused greater increases in intraepithelial mucosubstances in the septum than those elicited by OVA alone. These results demonstrate that exposure to ozone exacerbates epithelial and inflammatory responses associated with allergen challenge. In addition, coexposure of these agents enhanced the induced production of nasal mucosubstances caused by either agent alone.
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PMID:Enhancement of nasal inflammatory and epithelial responses after ozone and allergen coexposure in Brown Norway rats. 1201 88

The aim of this study was to develop and characterize a new model for evaluating nasal congestion in rats by using whole body plethysmography (WBP)-free moving application. Brown Norway rats were sensitized with 10% toluene-2, 4-diisocyanate (TDI) solution, and nasal congestion was provoked with 5% TDI. An increase in the enhanced pause (Penh) was recognized after being challenged with TDI. In addition, a significant increase in the Penh was observed following the intranasal application of histamine in TDI sensitized rats. Histamine H1 antagonists, such as chlorpheniramine and ketotifen suppressed the increase of Penh during the early-phase response. On the other hand, epinastine suppressed the increase of Penh in both the early and late phase responses. In conclusion, we developed an allergic rhinitis model that includes nasal congestion symptoms in Brown Norway rats, and this model may be useful for evaluating the effects of drugs on nasal congestion.
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PMID:Nasal congestion model in Brown Norway rats and the effects of some H1-antagonists. 1654 6

Fluticasone furoate (FF) is a novel enhanced-affinity glucocorticoid that has been developed as topical therapy for allergic rhinitis. The pharmacological properties of FF have been investigated using a number of in vitro experimental systems. FF demonstrated very potent glucocorticoid activity in several key pathways downstream of the glucocorticoid receptor (GR) as follows: the transrepression nuclear factor-kappaB (NF-kappaB) pathway, the transactivation glucocorticoid response element pathway, and inhibition of the proinflammatory cytokine tumor necrosis factor-alpha. Furthermore, FF showed the greatest potency compared with other glucocorticoids for preserving epithelial integrity and reducing epithelial permeability in response to protease- and mechanical-induced cell damage. FF showed a 30- to >330,000-fold selectivity for GR-mediated inhibition of NF-kappaB vs. the other steroid hormone receptors, substantially better than a number of other clinically used glucocorticoids. In studies examining the respiratory tissue binding properties of glucocorticoids, FF had the largest cellular accumulation and slowest rate of efflux compared with other clinically used glucocorticoids, consistent with greater tissue retention. The in vivo anti-inflammatory activity of FF was assessed in the Brown Norway rat ovalbumin-induced lung eosinophilial model of allergic lung inflammation. At a dose of only 30 microg, FF achieved almost total inhibition of eosinophil influx in the lung, an inhibition that was greater than that seen with the same dose of fluticasone propionate. In conclusion, the potent and selective pharmacological profile of FF described here could deliver an effective, safe, and sustained topical treatment of respiratory inflammatory diseases such as allergic rhinitis and asthma.
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PMID:Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease. 1757 11

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