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Background: Complementary and alternative medicine, including Japanese traditional medicine (JTM), has been used for various allergic diseases, but the evidence is limited. Shoseiryuto (Xiao-Qing-Long-Tang), one of the representative JTM drugs, is frequently used to treat allergic rhinitis (AR). However, its efficacy for seasonal AR has not been fully established. Using an Environmental challenge chamber (ECC), we evaluated the therapeutic effects of shoseiryuto on AR induced by Japanese cedar pollen (JCP). Methods: A placebo-controlled double-blind crossover study with shoseiryuto was conducted using the ECC. The shoseiryuto or placebo was orally administered from 2 weeks before the exposure test. The pollen exposure test was conducted for 3 h, and the pollen concentration was set at 8000 pollen/m3. The primary endpoint of the study was the total nasal symptom score (TNSS) during pollen exposure. A physician certified by the Japanese Society of Oriental Medicine as a specialist checked each participant's “pattern”, a comprehensive expression of signs obtained from individual patients' subjective symptoms and other personal findings. Blood samples collected just before the first pollen exposure were stimulated with cedar antigens and used for immunological studies. Results: The results of the 46 participants were analyzed, and no significant side effects were detected. There was no significant difference in TNSS during pollen exposure for 3 h in the ECC between the shoseiryuto and placebo groups. However, some symptoms were improved in the shoseiryuto group after leaving the ECC. There was no significant correlation between the “fluid retention pattern” and TNSS. In immunological studies, shoseiryuto did not inhibit Th2-type cytokine production and mRNA expression. Conclusions: Oral administration of shoseiryuto from 2 weeks before pollen exposure did not prevent or inhibit immediate symptoms of AR induced by JCP in the ECC. Further study is needed to reevaluate the shoseiryuto specific “pattern” in JTM.

Background: Recently, the role of the epigenome in allergies has been receiving increasing attention. Although several genes that are methylated in relation to serum immunoglobulin E (IgE) concentration have been reported by epigenome-wide association studies, little is known about the DNA methylation sites associated with the symptoms and severity of cedar pollinosis (CP). Objective: Our aim was to analyze the association between DNA methylation and the symptoms and severity of CP in peripheral blood mononuclear cells (PBMCs) and nasal mucosa scraping cells (NMSCs). Methods: We recruited 70 participants during the cedar pollen dispersal season. IgE levels were measured by a fluorescence enzyme immunoassay. We analyzed DNA methylation of acyl-CoA thioesterase 7 (ACOT7), mucin 4 (MUC4), schlafen 12 (SLFN12), lysophosphatidylcholine acyltransferase 2 (LPCAT2), and interleukin-4 (IL4) in PBMCs and NMSCs using bisulfite next-generation sequencing; the correlation of DNA methylation with non-specific IgE and cedar pollen-specific IgE levels in peripheral blood samples was also investigated. Symptom severity and DNA methylation were investigated in 15 untreated CP patients. Results: Non-specific IgE levels showed a significant negative correlation with average IL4 methylation in PBMCs (r = −0.46, P < 0.0001) but not with methylation of ACOT7, MUC4, SLFN12, and LPCAT2. Cedar pollen-specific IgE levels showed a significant negative correlation with average IL4 and MUC4 methylation in PBMCs (r = −0.31, P = 0.01 and r = −0.241, P = 0.046, respectively) but not with methylation of ACOT7, SLFN12, and LPCAT2. The methylation of some genes in NMSCs was not significantly correlated with IgE levels. The mean methylation of LPCAT2 in NMSCs showed a decreasing trend with increasing severity of CP (P = 0.027). Conclusion: LPCAT2 methylation in NMSCs may reflect the severity of CP and could be used as a novel biomarker to identify suitable treatment options for CP. [ABSTRACT FROM AUTHOR]

Background: Studies show that immunoglobulin E (IgE) is produced in the local nasal mucosa in allergic rhinitis patients. However, no study involved the measurement of IgE levels in the local nasal mucosal tissue in allergic rhinitis patients. This study aimed to measure the local IgE levels in the nasal mucosal tissue and to compare the levels of total IgE and specific IgEs in the serum and the inferior turbinate nasal mucosa in allergic rhinitis patients using the AlaSTAT 3gAllergy assay (Siemens Healthcare Diagnostics AG, Erlangen, Germany). Methods: Total IgE antibodies and allergen-specific IgE antibodies in each sample of nasal mucosal tissue from 11 allergic rhinitis patients were measured with the AlaSTAT 3gAllergy assay. We compared the levels of total IgE and IgEs specific for house dust (HD), mites, and cedar pollen in the serum and the inferior turbinate. Results: The total IgE levels and the cedar pollen-specific IgE levels in the inferior turbinate mucosal tissue correlated significantly with their respective levels in serum. The HD- and mite-specific IgE levels in the inferior turbinate mucosal tissue did not correlate significantly with their respective levels in the serum. Conclusions: Our results evaluating the correlations between nasal mucosal and serum levels of antigen-specific IgE indicate that IgE produced in the nasal mucosa affects the IgE levels in the serum, especially the cedar pollen-specific IgE.

Abstract Background About one-third of the Japanese population suffers from Japanese cedar pollinosis, which is frequently accompanied by Japanese cypress pollinosis. Recently, a novel major Japanese cypress pollen allergen, Cha o 3, was discovered. However, whether a Cha o 3 homolog is present in Japanese cedar pollen remains to be determined. Methods Western blot analysis was performed using Cha o 3–specific antiserum. In addition, cloning of the gene encoding Cry j 4 was conducted using total cDNA from the male flower of Japanese cedar trees. Allergen potency and cross-reactivity were investigated using a T-cell proliferation assay, basophil activation test, and ImmunoCAP inhibition assay. Results A low amount of Cha o 3 homolog protein was detected in Japanese cedar pollen extract. The deduced amino acid sequence of Cry j 4 showed 84% identity to that of Cha o 3. Cross-reactivity between Cry j 4 and Cha o 3 was observed at the T cell and IgE levels. Conclusions Cry j 4 was discovered as a counterpart allergen of Cha o 3 in Japanese cedar pollen, with a relationship similar to that between Cry j 1–Cha o 1 and Cry j 2–Cha o 2. Our findings also suggest that allergen-specific immunotherapy (ASIT) using Japanese cedar pollen extract does not induce adequate immune tolerance to Cha o 3 due to the low amount of Cry j 4 in Japanese cedar pollen. Therefore, ASIT using Cha o 3 or cypress pollen extract coupled with Japanese cedar pollen extract is required in order to optimally control allergy symptoms during Japanese cypress pollen season. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A two-domain family GH19 chitinase from Japanese cedar ( Cryptomeria japonica) pollen, CJP-4, which consists of an N-terminal CBM18 domain and a GH19 catalytic domain, is known to be an important allergen, that causes pollinosis. We report here the resonance assignments of the NMR spectrum of CJP-4. The backbone resonances were almost completely assigned, and the secondary structure was estimated based on the chemical shift values. The addition of a chitin dimer to the enzyme solution perturbed the chemical shifts of the resonances of amino acid residues forming a long extended binding site spanning from the CBM18 domain to the GH19 catalytic domain. [ABSTRACT FROM AUTHOR]

Background: There has been an increasing interest in monitoring the fractional concentrations of exhaled NO (FeNO) levels in allergic rhinitis (AR) patients. In the present study, we examined whether the nasal FeNO measurement might reflect the degree of local allergic inflammation as well as subjective symptoms. Methods: The FeNO measurement was performed using a handheld electrochemical analyzer (NObreath®) with a nose adaptor. In the cross-sectional study, 56 patients with perennial AR patients, 18 AR patients with bronchial asthma (BA), 12 patients with vasomotor rhinitis, and 30 normal subjects were enrolled. For the follow-up study, 12 seasonal allergic rhinitis (SAR) patients against Japanese cedar and 10 perennial AR patients who underwent laser surgery were examined. Results: The AR patients and vasomotor rhinitis patients showed significantly higher oral FeNO levels as compared with the normal subjects. The nasal FeNO levels were significantly higher in the perennial AR patients with or without BA than in the normal subjects and vasomotor rhinitis patients. There were positive correlations between the nasal symptom scores and FeNO levels. The SAR patients showed a significant decrease in the nasal FeNO level after the pollen dispersion season. In addition, the therapeutic effects of laser surgery in the AR patients accompanied a significant reduction in the nasal FeNO levels one month after treatment. Conclusions: The nasal FeNO measurement by NObreath® is easy to perform and suitable for monitoring AR patients in various treatment modalities. Furthermore, it may have potential usefulness as a tool to improve daily clinical care.

We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST) scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0) in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6). The patients showed positive immediate (20 min in both sisters) and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister) reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

Background: Japanese cedar pollen-induced allergic rhinitis in a guinea pig model clearly induced not only sneezing but also biphasic nasal blockage. To date, there have only been a few reports on models of murine allergic rhinitis which clearly show nasal blockage. Therefore, in order to try and develop such a model, we administered multiple dosages of intranasal pollen or purified antigen protein Cry j 1. Methods: B10.S mice were sensitized by intranasal instillations of either pollen extract or Cry j 1 twice a day for 7 days, which was adsorbed on Al(OH)3. Subsequently, once a week, the mice were given multiple intranasal instillation challenges of either the pollen suspension or Cry j 1 and the frequency of sneezing was observed after respective challenges were made. Specific airway resistance (sRaw) was measured as an indicator for nasal blockage. Cry j 1-specific IgE levels were measured using an enzyme-linked immunosorbent assay. Results: The serum Cry j 1-specific IgE level showed clear elevation only in the group sensitized by Cry j 1 + Al(OH)3 and then challenged by Cry j 1. No elevations were seen in the groups sensitized by pollen extract + Al (OH)3 followed by a pollen suspension challenge. There was an immediate increase in sneezing after challenges in all of the sensitized-challenged groups. Nevertheless, no increases in sRaw in any of the groups were detected at any of the time points during the 8 hours following the challenges. Conclusions: Cry j 1 may be more effective than crude antigens for efficient sensitization/challenge in mice. No increase in sRaw occurred, even in mice that possessed high amounts of Cry j 1-specific IgE and that exhibited sneezing.

Background Studies show that immunoglobulin E (IgE) is produced in the local nasal mucosa in allergic rhinitis patients. However, no study involved the measurement of IgE levels in the local nasal mucosal tissue in allergic rhinitis patients. This study aimed to measure the local IgE levels in the nasal mucosal tissue and to compare the levels of total IgE and specific IgEs in the serum and the inferior turbinate nasal mucosa in allergic rhinitis patients using the AlaSTAT 3gAllergy assay (Siemens Healthcare Diagnostics AG, Erlangen, Germany). Methods Total IgE antibodies and allergen-specific IgE antibodies in each sample of nasal mucosal tissue from 11 allergic rhinitis patients were measured with the AlaSTAT 3gAllergy assay. We compared the levels of total IgE and IgEs specific for house dust (HD), mites, and cedar pollen in the serum and the inferior turbinate. Results The total IgE levels and the cedar pollen-specific IgE levels in the inferior turbinate mucosal tissue correlated significantly with their respective levels in serum. The HD- and mite-specific IgE levels in the inferior turbinate mucosal tissue did not correlate significantly with their respective levels in the serum. Conclusions Our results evaluating the correlations between nasal mucosal and serum levels of antigen-specific IgE indicate that IgE produced in the nasal mucosa affects the IgE levels in the serum, especially the cedar pollen-specific IgE. [ABSTRACT FROM AUTHOR]

Background: Avoidance of allergens is one of the most effective treatments of allergenic diseases, including pollinosis. Although various masks and goggles for pollinosis sufferers are commercially available, little work has been done on preventing adhesion of pollen to the human body and clothes. We have examined the effect of polymer coating on adhesion of cedar pollen to skin, hair and fabrics, and found that a lecithin polymer (LP), containing both cationic and anionic sites, is highly effective in reducing adhesion levels. Methods: We evaluated the changes in electrostatic charge and frictional coefficient of sample surfaces after coating with an anionic polymer (AP), a cationic polymer (CP), a nonionic polymer (NIP), or LP (each applied by spraying 0.10% polymer solution in ethanol/water). Pollen adhesion level was evaluated by observation of the number of cedar pollen particles on video microscope (VMS) images and by quantification of cedar pollen antigen Cry j1 with a sandwich ELISA system. Adhesion of pollen to human skin or hair was also examined by VMS observation. Results: LP-coated samples showed a significant reduction in electrostatic charge level and frictional coefficient. We presumed that these properties are closely related to the significant reduction in the adhesion level of cedar pollen or Cry j1 compared with CP, AP or NIP-coated samples. A similar effect was seen on LP-treated skin, and LP-treated waxed hair. Conclusions: Our results suggest that coating with LP could help in the management of pollinosis by reducing the contact level of patients with cedar pollen antigens.

Background: We investigated the effect of sublingual immunotherapy (SLIT) on Japanese cedar and cypress pollinosis in a mass scattering year of cedar pollen (total counts: 12353 grains/cm 2 , approximately four times the average)., Methods: SLIT patients of 84 in the first year, 107 in the second year and 67 in the third year treated with Cedarcure ® were included. During the 2023 cedar and cypress pollen dispersal season, nasal and eye symptoms and general symptoms were examined using a visual analog scale (VAS)., Results: The VAS during the cedar season significantly decreased to improve with the number of years of SLIT, but the VAS during the cypress period slightly increased. A questionnaire survey before SLIT revealed that only 0.9% to 3.6% of patients had strong cypress symptoms. However, sneezing (p＜0.01), rhinorrhea, itchy eyes and total symptoms (p＜0.05) in the third year of SLIT were significantly stronger during the cypress period than during the cedar period. The VAS of total symptoms during the Japanese cedar pollen season were not affected by the pollen count, and the cure rate was affected by SLIT in the third year., Conclusion: The clinical efficacy of cedar SLIT on cedar pollinosis was high even in a mass scattering year, and the effect increased with the number of years of treatment. On the other hand, it was shown that the clinical efficacy on cypress pollinosis was insufficient.

ABSTRACT Previous studies using experimental animal models have reported the beneficial effects of probiotics on allergic responses; however, their long-term effects on allergic nasal symptoms in clinical settings have not yet been elucidated in detail. In the present study, a guinea pig allergic rhinitis model involving repeated inhalation challenges with a natural allergen, Japanese cedar pollen, was used to examine the longitudinal effects of Bifidobacterium bifidum G9-1 (BBG9-1) on allergic nasal symptoms. BBG9-1 was administered orally once a day. Amelioration of nasal blockage was consistently observed throughout the experimental period in the BBG9-1-treated group. Although challenge-induced sneezing was not significantly inhibited in the BBG9-1-treated group, prolonged treatment with BBG9-1 slightly reduced the frequency of sneezing. Antigen-specific IgE antibody production was also not inhibited in the BBG9-1-treated group. Increases in the numbers of eosinophils and neutrophils in nasal cavity lavage fluid collected after pollen challenge were almost completely suppressed by BBG9-1 treatment, whereas those in mast cell mediators, histamine and cysteinyl leukotrienes were not. In contrast, increases in the levels of nitric oxide metabolites were potently suppressed. Furthermore, prolonged BBG9-1 treatment markedly suppressed exogenous leukotriene D4-induced nasal blockage. Thus, prolonged oral administration of BBG9-1 suppresses Japanese cedar pollen-induced allergic nasal symptoms. The inhibitory mechanisms responsible may involve reductions in the responsiveness of target organs, such as endothelial cells in nasal mucosal blood vessels, to chemical mediators. [ABSTRACT FROM AUTHOR]

The major allergen, Cry j 1, was isolated from Japanese cedar Cryptomeria japonica (Cry j) pollen and was shown to react with immunoglobulin E antibodies in the sera from pollinosis patients. We previously reported that the frequency of HLA-DP5 was significantly higher in pollinosis patients and the immunodominant peptides from Cry j 1 bound to HLA-DP5 to activate Th2 cells. In the present study, we determined the crystal structure of the HLA-DP5 heterodimer in complex with a Cry j 1-derived nine-residue peptide, at 2.4 Å resolution. The peptide-binding groove recognizes the minimal peptide with 10 hydrogen bonds, including those between the negatively charged P1 pocket and the Lys side chain at the first position in the peptide sequence. We confirmed that HLA-DP5 exhibits the same Cry j 1-binding mode in solution, through pull-down experiments using structure-based mutations of Cry j 1. We also identified the characteristic residues of HLA-DP5 that are responsible for the distinct properties of the groove, by comparing the structure of HLA-DP5 and the previously reported structures of HLA-DP2 in complexes with pDRA of the self-antigen. The comparison revealed that the HLA-DP5·pCry j 1 complex forms several hydrogen bond/salt bridge networks between the receptor and the antigen that were not observed in the HLA-DP2·pDRA complex. Evolutionary considerations have led us to conclude that HLA-DP5 and HLA-DP2 represent two major groups of the HLA-DP family, in which the properties of the P1 and P4 pockets have evolved and acquired the present ranges of epitope peptide-binding specificities. [ABSTRACT FROM AUTHOR]

Radionuclides released during the Fukushima Daiichi nuclear accident caused altitude-dependent surface contamination in the mountainous areas of Japan. To explore the possible cloudwater deposition that formed a distinctive contamination profile, data from pollen sensors deployed nationwide were analyzed. Utilizing the polarization of scattered light, Cedar pollen and water droplets were distinguished. On March 15, when surface contamination was simulated in previous studies, dense clouds with high droplet number concentrations were observed outside the 137 Cs surface deposition areas, indicating that the sensor sites were immersed amid cloud layers. In contrast, cloud droplets with moderate number concentrations were measured at altitudes of approximately 570-840 m, which overlapped with the surface contamination areas. Considering the existing knowledge on vertical gradients of cloudwater composition, these suggest that contaminated cloud droplets were localized near the cloud base where a moderate number concentration of cloud droplets was measured. A formation process was proposed for the observed vertical distribution, that is, surface contamination occurred intensively at the contact line between the cloud base and mountain slopes via cloudwater deposition, and the descending cloud base formed the contamination zone. This study sheds light on the deposition processes of radionuclides, which have not previously been clarified.

The article presents a case study of a 14-year-old girl who was given a sublingual drop of JC pollen as SLIT. The article discusses that she developed erythema with pruritus; she had JC pollinosis but no other allergic history, including atopic dermatitis, asthma, or food allergy; and she was referred to our hospital on day 5, and administrated oral prednisolone at 20 mg/day but erythema, itching, and fever remained, and she was hospitalized on day.

Injection of a Japanese cedar pollen suspension into silkworm hemolymph kills the silkworms. A certain species of bacteria proliferated in the hemolymph of the dead silkworms. A 16S rDNA analysis demonstrated that the proliferating bacteria were Bacillus cereus, Bacillus thuringiensis, Bacillus weihenstephanensis, and Bacillus amyloliquefaciens. Among them, B. cereus, B. thuringiensis, and B. weihenstephanensis exhibited hemolysis against sheep red blood cells and were lethal to mice. A culture filtrate of B. amyloliquefaciens showed enzyme activity toward the pectic membrane of cedar pollen. These results suggest that silkworms as an animal model are useful for evaluating the pathogenicity of bacteria attached to cedar pollen. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that chymase activity was increased in allergic conjunctivitis patients and this activity was correlated with the severity of the disease. However, the precise roles of chymase in allergic conjunctivitis are unclear, and whether chymase inhibitors are effective for allergic conjunctivitis has not been reported even in experimental animal models. In this study, the roles of chymase in the pathogenesis were evaluated using a selective chymase inhibitor, ONO-WH-236, in a guinea pig model of allergic conjunctivitis induced by cedar pollen. Sensitized guinea pigs were challenged by the pollen, followed by assessing redness and edema in the conjuntiva, and counting the frequency of eye scratching as an itch-associated response. Treatment with the ONO-WH-236 (40 and 80 mg/kg, p.o.) dose-dependently inhibited the induction of redness, edema and scratching behavior. An anti-histaminic drug, ketotifen (3 mg/kg, p.o.), also significantly inhibited conjunctivitis symptoms. Chymase activity was increased in ophthalmic lavage fluid immediately after the pollen challenge. The increase in chymase activity was inhibited by in vivo treatment with ONO-WH-236. Interestingly, increased histamine in the ophthalmic lavage fluid immediately after the challenge was also inhibited by the chymase inhibitor. Administration of human recombinant chymase by eye dropping (0.09 and 0.9 μg/eye) dose-dependently induced scratching behavior, which was inhibited by not only ONO-WH-236 but also ketotifen; however, chymase administration induced only weak redness in the conjunctiva, which was resistant to treatment with anti-histaminic drugs. In conclusion, it was suggested that chymase was released from mast cells after antigen challenge, followed by the induction of conjunctivitis symptoms through histamine release from mast cells. Thus, chymase could be a potential target for pharmacotherapy for allergic conjunctivitis. [Copyright &y& Elsevier]

Background: There has been an increasing interest in monitoring the fractional concentrations of exhaled NO (FeNO) levels in allergic rhinitis (AR) patients. In the present study, we examined whether the nasal FeNO measurement might reflect the degree of local allergic inflammation as well as subjective symptoms. Methods: The FeNO measurement was performed using a handheld electrochemical analyzer (NObreath®) with a nose adaptor. In the cross-sectional study, 56 patients with perennial AR patients, 18 AR patients with bronchial asthma (BA), 12 patients with vasomotor rhinitis, and 30 normal subjects were enrolled. For the follow-up study, 12 seasonal allergic rhinitis (SAR) patients against Japanese cedar and 10 perennial AR patients who underwent laser surgery were examined. Results: The AR patients and vasomotor rhinitis patients showed significantly higher oral FeNO levels as compared with the normal subjects. The nasal FeNO levels were significantly higher in the perennial AR patients with or without BA than in the normal subjects and vasomotor rhinitis patients. There were positive correlations between the nasal symptom scores and FeNO levels. The SAR patients showed a significant decrease in the nasal FeNO level after the pollen dispersion season. In addition, the therapeutic effects of laser surgery in the AR patients accompanied a significant reduction in the nasal FeNO levels one month after treatment. Conclusions: The nasal FeNO measurement by NObreath® is easy to perform and suitable for monitoring AR patients in various treatment modalities. Furthermore, it may have potential usefulness as a tool to improve daily clinical care. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis involves inflammation of the nasal passages. The use of nasal steroids is generally very effective in providing significant symptom relief. However, compliance for their use is sometimes poor. Methods: To examine the efficacy of early intervention (before pollen dispersal) with oral cysteinyl leukotriene receptor antagonists (LTRA) on pollinosis in patients with allergy to cedar and Japanese cypress pollens, groups of subjects were treated with LTRA or a placebo for 4 weeks at the beginning of the cedar pollen dispersal season. Subsequently, all patients received nasal steroid therapy concomitantly with LTRA throughout the remaining period of the pollen dispersal season. The effects of such early treatment with LTRA on pollinosis were investigated using symptom scores from an allergy diary and quality of life (QOL) scores. Results: Sneezing and nasal congestion scores were significantly lower in the LTRA-pretreated subjects than observed in the placebo-pretreated patients between weeks 4 and 6 and weeks 3 and 5, respectively. QOL scores improved significantly in all domains after concomitant therapy with nasal steroids. The percent improvement in the nasal congestion score after the concomitant therapy was significantly higher in the LTRA group (69%) than in the placebo group (41%). Conclusion: Significant differences observed in symptoms and in QOL effects between LTRA- and placebo-pretreated patients and the absence of major adverse effects noted in these studies suggest that early intervention with LTRA is beneficial and safe and should be considered in the management of pollinosis-associated allergic rhinitis. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Japanese cedar pollen-induced allergic rhinitis in a guinea pig model clearly induced not only sneezing but also biphasic nasal blockage. To date, there have only been a few reports on models of murine allergic rhinitis which clearly show nasal blockage. Therefore, in order to try and develop such a model, we administered multiple dosages of intranasal pollen or purified antigen protein Cry j 1. Methods: B10.S mice were sensitized by intranasal instillations of either pollen extract or Cry j 1 twice a day for 7 days, which was adsorbed on AI(OH)3. Subsequently, once a week, the mice were given multiple intranasal instillation challenges of either the pollen suspension or Cry j 1 and the frequency of sneezing was observed after respective challenges were made. Specific airway resistance (sRaw) was measured as an indicator for nasal blockage. Cry j 1-specific IgE levels were measured using an enzyme-linked immunosorbent assay. Results: The serum Cry j 1-specific IgE level showed clear elevation only in the group sensitized by Cry j 1 + AI(OH)3 and then challenged by Cry j 1. No elevations were seen in the groups sensitized by pollen extract + AI (OH)3 followed by a pollen suspension challenge. There was an immediate increase in sneezing after challenges in all of the sensitized-challenged groups. Nevertheless, no increases in sRaw in any of the groups were detected at any of the time points during the 8 hours following the challenges. Conclusions: Cry j 1 may be more effective than crude antigens for efficient sensitization/challenge in mice. No increase in sRaw occurred, even in mice that possessed high amounts of Cry j 1-specific IgE and that exhibited sneezing. [ABSTRACT FROM AUTHOR]

Abstract: TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone) is a novel quinolinone derivative that has been demonstrated to possess an anti-oxidative activity against peroxynitrite, a potent oxidant, that is generated by the reaction of nitric oxide with superoxide anions. The current study describes the inhibitory effect of TA-270 on the biphasic nasal blockage induced by repeated antigen challenge in an allergic rhinitis guinea pig model. In the present in vitro study, TA-270 potently inhibited the oxidative reaction induced by peroxynitrite (IC50 =79 nM). In addition, TA-270 (0.3–30 mg/kg, p.o.) dose-dependently inhibited peroxynitrite (3 mM, 10 μl/nostril)-induced nasal blockage in guinea pigs. In the antigen-induced allergic rhinitis model, TA-270 (0.3, 3, and 30 mg/kg, p.o.) given 1 h before the antigen challenge suppressed early phase nasal blockage by 36%, 42%, and 63%, respectively. Furthermore, TA-270 (0.3, 3, and 30 mg/kg, p.o.) showed a relatively strong suppression of late phase nasal blockage (39%, 62%, and 72%, respectively). The late phase nasal blockage was significantly inhibited (61%) even when TA-270 (30 mg/kg, p.o.) was administered 18 h before the antigen challenge. In conclusion, TA-270 improved antigen-induced nasal blockage, probably through its peroxynitrite scavenging action, and the effect was sustained for at least 18 h. Thus, TA-270 would be expected to relieve nasal blockage in allergic rhinitis patients. [Copyright &y& Elsevier]

Background Airborne contact dermatitis to cedar pollen is a recently identified disease that generally affects individuals with cedar pollinosis of the nasal and/or ocular symptoms, as well as some patients with atopic dermatitis. Objective To elucidate the pathological mechanisms of cedar pollen dermatitis. Methods We established a mouse model of cedar pollen dermatitis by epicutaneous sensitization with Japanese cedar pollen antigen (Ag). Results Histologically, there was marked dermal cellular infiltrate, including eosinophils and mast cells, with epidermal thickening. The induction of dermatitis was accompanied by production of cedar pollen-specific IgE. In the lesional skin, IL-13, IL-18, eotaxin/chemokine (C-C motif) ligand (CCL) 11, regulated upon activation, normal T cell expressed and secreted/CCL5, macrophage-derived chemokine/CCL22 and thymus and activation-regulated chemokine/CCL17, but not IL-4 and IFN-γ, were produced. Mast cell-deficient WBB6F1-W/Wv mice failed to develop cedar pollen dermatitis, although regional lymph node cells proliferated in response to Cryptomeria japonica (Cry j) 1 and Cry j2 Ags in vitro. Surprisingly, the induction of dermatitis was independent of STAT6/IgE. In contrast, mice deficient in CRTH2, a receptor for prostaglandin D2 (PGD2), showed diminished inflammation. Consistent with this, ramatroban, a CRTH2 antagonist, significantly inhibited inflammatory cell infiltration. Conclusion These data suggest that PGD2–CRTH2 signalling contributes to inflammation in cedar pollen dermatitis, and unlike cedar pollinosis of the nasal mucosa, STAT6 is not a therapeutic target for treatment. [ABSTRACT FROM AUTHOR]

Background: Avoidance of allergens is one of the most effective treatments of allergenic diseases, including pollinosis. Although various masks and goggles for pollinosis sufferers are commercially available, little work has been done on preventing adhesion of pollen to the human body and clothes. We have examined the effect of polymer coating on adhesion of cedar pollen to skin, hair and fabrics, and found that a lecithin polymer (LP), containing both cationic and anionic sites, is highly effective in reducing adhesion levels. Methods: We evaluated the changes in electrostatic charge and frictional coefficient of sample surfaces after coating with an anionic polymer (AP), a cationic polymer (CP), a nonionic polymer (NIP), or LP (each applied by spraying 0.10% polymer solution in ethanol/water). Pollen adhesion level was evaluated by observation of the number of cedar pollen particles on video microscope (VMS) images and by quantification of cedar pollen antigen Cry j1 with a sandwich ELISA system. Adhesion of pollen to human skin or hair was also examined by VMS observation. Results: LP-coated samples showed a significant reduction in electrostatic charge level and frictional coefficient. We presumed that these properties are closely related to the significant reduction in the adhesion level of cedar pollen or Cry j1 compared with CP, AP or NIP-coated samples. A similar effect was seen on LP-treated skin, and LP-treated waxed hair. Conclusions: Our results suggest that coating with LP could help in the management of pollinosis by reducing the contact level of patients with cedar pollen antigens. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the relation between various specific class E immunoglobulins (IgE) in serum and allergic conjunctivitis in spring.Methods: Forty patients with allergic conjunctivitis and fifty healthy volunteers were selected for this trial. Total IgE and specific IgE to twelve inhalant allergens were measured using the CAP system.Results: Specific IgE levels caused by cedar and cypress pollen, house dust, Dermatophagoides pteronyssinus, acarus, and moth allergens were higher in the allergy group than in the control group. No correlation was proven between the specific IgE levels and the total IgE level. The highest positivity rate for a specific allergen in patients with allergic conjunctivitis was 52.5% for cedar pollen, followed by cypress pollen at 37.5%.Conclusions: These results suggest that cypress pollen was the largest cause of allergic conjunctivitis and that the total IgE level had no correlation with each specific IgE. [ABSTRACT FROM AUTHOR]

Background: The prevalence of allergic disease is increasing worldwide, but its influence on the clinical course of autoimmune diseases is unknown. Objective: The purpose of this study was to assess the effect of seasonal allergic rhinitis on the clinical course of Graves’ disease, which has been considered a Th2-dominant autoimmune disease. Methods: Ten patients with Graves’ disease, who were considered to be in a state of remission or near remission, were serially examined for 18 months starting from August. Five of them had seasonal allergic rhinitis due to Japanese cedar pollen, and the remaining patients had no such allergic disorders. Peripheral eosinophil counts, serum concentrations of cedar-pollen-specific IgE, anti-TSH-receptor antibody, anti-thyroid-peroxidase antibody and antithyroglobulin antibody were assessed at 2- to 4-month intervals. Serum thyroid hormones and TSH levels were also measured to evaluate disease activity. Results: All patients with pollinosis had attacks of allergic rhinitis caused by cedar pollen in early March. Subsequently, peripheral eosinophil counts, pollen-specific IgE activity and serum levels of anti-thyroid-peroxidase and antithyroglobulin autoantibodies markedly increased. Serum levels of anti-TSH-receptor antibody increased in 3 patients in association with an increase in serum thyroid hormones but were always negative in 2 patients. The control patients without pollinosis showed no consistent change of these parameters. Conclusions: Seasonal allergic rhinitis aggravated the clinical course of Graves’ disease and induced an increase in serum antithyroid autoantibody concentrations as well as an increase in pollen-specific IgE concentration. These data suggest that environmental antigens induce not only local allergic reactions, but also stimulate thyroid immune reactions toward Th2 proliferation, and finally aggravate Th2-dependent autoimmune thyroid disease.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

TAK-427 {2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate} is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1–10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist. [Copyright &y& Elsevier]

ABSTRACT Background: An increase in Japanese cedar pollen counts is the probable reason for the increase in the number of Japanese cedar hay fever patients. To determine whether local antigen exposure dose affects sensitization with cedar pollen, we compared serum levels of specific IgE antibody in rats exposed to higher and lower doses of cedar pollen antigen through the nose. Methods: Serum levels of cedar pollen-specific IgE antibody was examined in Brown Norway rats exposed to a higher dose of (20 μg) Cry j I, a lower dose (2 μg) of Cry j I or no dose for 6 months. Serum levels of cedar pollen-specific IgE antibody were measured by reverse IgE-capture ELISA. The extent of local eosinophilia in the nasal, laryngeal and tracheal mucosa of rats exposed higher and lower doses of cedar pollen antigen and controls were observed microscopically. Results: The mean serum levels of specific IgE antibody in rats exposed to the higher dose were significantly higher than those in rats exposed to the lower dose, and the mean levels in rats in the lower-dose group were significantly higher than in controls. The extent of eosinophilia in the nasal mucosa in the higher-dose group was significantly greater than in controls, but no significant differences between the lower-dose group and controls were found. The extent of eosinophilia in the laryngeal mucosa in the higher-dose group was significantly greater than that in the lower-dose group and in controls. Only a small degree of eosinophilia was observed in the trachea of all three groups. Conclusions: Local exposure dose of the upper airway to cedar pollen may affect sensitization. [ABSTRACT FROM AUTHOR]

Background: Complementary and alternative medicine, including Japanese traditional medicine (JTM), has been used for various allergic diseases, but the evidence is limited. Shoseiryuto (Xiao-Qing-Long-Tang), one of the representative JTM drugs, is frequently used to treat allergic rhinitis (AR). However, its efficacy for seasonal AR has not been fully established. Using an Environmental challenge chamber (ECC), we evaluated the therapeutic effects of shoseiryuto on AR induced by Japanese cedar pollen (JCP)., Methods: A placebo-controlled double-blind crossover study with shoseiryuto was conducted using the ECC. The shoseiryuto or placebo was orally administered from 2 weeks before the exposure test. The pollen exposure test was conducted for 3 h, and the pollen concentration was set at 8000 pollen/m 3 . The primary endpoint of the study was the total nasal symptom score (TNSS) during pollen exposure. A physician certified by the Japanese Society of Oriental Medicine as a specialist checked each participant's "pattern", a comprehensive expression of signs obtained from individual patients' subjective symptoms and other personal findings. Blood samples collected just before the first pollen exposure were stimulated with cedar antigens and used for immunological studies., Results: The results of the 46 participants were analyzed, and no significant side effects were detected. There was no significant difference in TNSS during pollen exposure for 3 h in the ECC between the shoseiryuto and placebo groups. However, some symptoms were improved in the shoseiryuto group after leaving the ECC. There was no significant correlation between the "fluid retention pattern" and TNSS. In immunological studies, shoseiryuto did not inhibit Th2-type cytokine production and mRNA expression., Conclusions: Oral administration of shoseiryuto from 2 weeks before pollen exposure did not prevent or inhibit immediate symptoms of AR induced by JCP in the ECC. Further study is needed to reevaluate the shoseiryuto specific "pattern" in JTM., (© 2022 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Background: We examined the clinical effects of Cedarcure ® tablets for sublingual immunotherapy (SLIT), and examined the enhancement of the effects over the years of treatment., Methods: The subjects were 358 patients who treated with SLIT (126 of third year of treatment, 102 of second year, 130 of first year) in a single clinic. The clinical efficacy was evaluated with visual analog scale (VAS) of nose, eye and total symptoms during the peak season of moderate amount of pollen dispersal (2485 grains/cm2/season) in 2022. Concomitant medication scores were calculated by Japanese guidelines. Because many cases of combined use of mite SLIT (dual SLIT) were included in the subjects, we compared cedar SLIT alone and dual SLIT as a secondary analysis., Results: Clinical efficacy improved with the years of treatment, and all assessments of VAS in the 3rd year were significantly better than in the 1st year of treatment (p<0.01). The third year was better with sneezing and nasal discharge than the 2nd year, and the 2nd year was better with itchy eyes than the 1st year (p<0.05). Drug scores were also lower in the 3rd and 2nd years than in the 1st year (p<0.05). Additional mite SLIT did not affect the results., Conclusion: Cedarcure ® showed enhancement of the effects over the years of treatment by the analysis up to the third year. Both Cedar SLIT alone and Dual SLIT showed similar efficacy on cedar pollinosis.