Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 142
Filtrar
1.
J Pharmacol Toxicol Methods ; 119: 107203, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35842185

RESUMO

Histamine is strongly associated with the onset of allergic conjunctivitis. The most recent cloned histamine H4 receptor antagonist is highly expected as a new therapeutic drug candidate. As a model for a therapeutic drug targeting the histamine H4 receptor, a mouse model in which conjunctivitis symptoms are induced by instilling 4-methylhistamine, a histamine H4 receptor agonist, has been reported. However, the affinity of the H4 receptor for histamine varies in species, and it is known that the histamine binding affinity for the guinea pig H4 receptor is closer to that for human receptor than mice receptor. In this paper, we investigated a possibility that a guinea pig model would become a drug efficacy evaluation model with higher evaluation accuracy than the mouse model. As a result, hyperemia was observed in the conjunctivae and iris of guinea pigs after instillation of 4-methylhistamine and specifically suppressed by the histamine H4 receptor antagonist. Unlikely to the previously reported mouse model, however, none of edema, increased vascular permeability or scratching behavior was observed, suggesting that there may be differences between mice and guinea pigs not only in the binding affinity of histamine to the H4 receptor but also in the biological reaction to 4-methylhistamine. Although the symptoms of allergic conjunctivitis do not appear comprehensively in the guinea pig model, results of this study indicated a possibility that this model can be used as a simple screening model in the early stages of drug development.


Assuntos
Conjuntivite Alérgica , Histamina , Cobaias , Camundongos , Humanos , Animais , Histamina/farmacologia , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/tratamento farmacológico , Conjuntivite Alérgica/prevenção & controle , Metilistaminas/efeitos adversos , Receptores Histamínicos/metabolismo , Receptores Histamínicos/uso terapêutico
2.
Invest Ophthalmol Vis Sci ; 63(5): 4, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35503228

RESUMO

Purpose: We aimed to explore the effect of lysine acetyltransferase KAT5 on allergic conjunctivitis (AC). Methods: The effect of KAT5 on inflammatory response during AC progression was analyzed in the experimental allergic conjunctivitis (EAC) mouse model. Results: The clinical score, permeability, total IgE, ovalbumin (OVA)-specific IgE, and IgG1/IgG2a were induced in the EAC mice, in which the overexpression of KAT5 could further enhance but KAT5 inhibitor NU9056 reduce the phenotypes. The eosinophilic infiltration was induced in EAC mice, in which the overexpression of KAT5 was able to further promote but NU9056 attenuate the phenotype. The expression of Eotaxin and RANTES and the inflammatory factors were upregulated in EAC mice and KAT5 overexpression increased, but NU9056 decreased the expression in the model. Significantly, the CD11c+ dendritic cells and CD4+ T cells infiltration in the conjunctiva was enhanced in EAC mice, whereas KAT5 overexpression induced but NU9056 suppressed the effect in the model. Mechanically, the phosphorylation of PI3K and Akt and the levels of histone H3 lysine 27 acetylation (H3K27ac) were enhanced in EAC mice, whereas the overexpression of KAT5 promoted and NU9056 repressed the phenotype in the mice. The enrichment of KAT5 and H3K27ac on PI3K promoter was increased in EAC mice, and the overexpression of KAT5 further enhanced the enrichment in the mice. Significantly, we observed similar results in the KAT5 knockout mice as well. Moreover, PI3K/AKT signaling inhibitor LY294002 reversed KAT5 overexpression-mediated phenotypes and inflammatory response after induction AC in vivo. Conclusions: Therefore we concluded that KAT5 inhibition protected against ocular inflammation by mediating the PI3K/AKT pathway in EAC mouse model.


Assuntos
Conjuntivite Alérgica , Animais , Conjuntivite Alérgica/genética , Conjuntivite Alérgica/prevenção & controle , Modelos Animais de Doenças , Imunoglobulina E , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
3.
Cells ; 10(12)2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34943868

RESUMO

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.


Assuntos
Alérgenos/imunologia , Betula/efeitos adversos , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/prevenção & controle , Dessensibilização Imunológica , Oryza/genética , Pólen/efeitos adversos , Vacinas de Plantas Comestíveis/imunologia , Administração Oral , Animais , Conjuntivite Alérgica/sangue , Imunoglobulina E/sangue , Interferon gama/metabolismo , Interleucina-4/metabolismo , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Plantas Geneticamente Modificadas , Baço/patologia , Linfócitos T Reguladores/imunologia
4.
J Pediatr ; 232: 183-191.e3, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33524387

RESUMO

OBJECTIVES: To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. STUDY DESIGN: In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF + LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. RESULTS: In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF + LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF + LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P < .001) for rice hydrolyzed formula vs EHCF + LGG; 2.62 (1.63-4.22, P < .001) for soy formula vs EHCF + LGG; 2.31 (1.42-3.77, P < .001) for EHWF vs EHCF + LGG; and 3.50 (2.23-5.49, P < .001) for amino acid-based formula vs EHCF + LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF + LGG cohort. CONCLUSIONS: The use of EHCF + LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.


Assuntos
Asma/prevenção & controle , Conjuntivite Alérgica/prevenção & controle , Dermatite Atópica/prevenção & controle , Tolerância Imunológica , Fórmulas Infantis , Hipersensibilidade a Leite/dietoterapia , Rinite Alérgica/prevenção & controle , Aminoácidos , Asma/epidemiologia , Asma/imunologia , Caseínas , Pré-Escolar , Conjuntivite Alérgica/epidemiologia , Conjuntivite Alérgica/imunologia , Dermatite Atópica/epidemiologia , Dermatite Atópica/imunologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Fórmulas Infantis/efeitos adversos , Fórmulas Infantis/química , Fórmulas Infantis/microbiologia , Lacticaseibacillus rhamnosus , Masculino , Hipersensibilidade a Leite/complicações , Hipersensibilidade a Leite/imunologia , Oryza , Probióticos/uso terapêutico , Estudos Prospectivos , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Glycine max , Resultado do Tratamento , Soro do Leite
5.
Ocul Immunol Inflamm ; 29(7-8): 1621-1626, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-32501774

RESUMO

Purpose: This study evaluated the efficacy and safety of once-daily Alcaftadine 0.25% (AGN-229666) for prevention of signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.Methods: This was a single-center, placebo-, and comparator-controlled study using the Ora-CAC® model of allergic conjunctivitis. The primary endpoint was ocular itching 16 hours after Alcaftadine 0.25% instillation; efficacy at 16 hours was compared with 0.1% Olopatadine, 4 hours after instillation. Secondary endpoints included conjunctival hyperemia.Results: 263 Japanese subjects were enrolled; 224 completed the trial. Alcaftadine 0.25% was statistically superior to vehicle for relief of ocular itching at 16 hours (p < .0001). Alcaftadine 0.25% at 16 hours was non-inferior to Olopatadine at 4 hours. Alcaftadine 0.25% was significantly better than vehicle for relief of conjunctival hyperemia. All treatments showed a low frequency of ocular adverse events.Conclusion: Once-daily Alcaftadine 0.25% is safe and effective in preventing signs and symptoms of Japanese cedar-pollen allergic conjunctivitis.


Assuntos
Benzazepinas/administração & dosagem , Conjuntivite Alérgica/prevenção & controle , Cryptomeria/química , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Imidazóis/administração & dosagem , Pólen/efeitos adversos , Administração Oftálmica , Adulto , Alérgenos/efeitos adversos , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/diagnóstico , Método Duplo-Cego , Feminino , Antagonistas não Sedativos dos Receptores H1 da Histamina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Olopatadina/administração & dosagem , Soluções Oftálmicas , Estudos Prospectivos , Resultado do Tratamento
6.
Minerva Pediatr ; 72(5): 343-357, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32731732

RESUMO

Allergen immunotherapy (AIT) is a well-established treatment for allergic respiratory diseases. It represents a cornerstone in the clinical management of allergic children since it is the only curative option to date able to modify the natural history of Ig-E mediated allergic diseases. Through a well-defined immunologic mechanism, AIT promotes regulatory T cells and cuts down the immune response induced by allergens. According to current guidelines based on up-to-date evidence, AIT should be offered to children with moderate-severe allergic rhinitis and/or controlled asthma starting from 5 years of age, further to an adequate risk-benefit assessment which includes patient's adherence to the treatment and a proper selection of the right product. Younger age and mild disease could be considered based on an individual evaluation. Both subcutaneous (SCIT) and sublingual (SLIT) routes of administration have a good efficacy and safety profile with safer outcomes for SLIT compared to SCIT. Only standardized products with documented evidence of clinical efficacy should be used. Although AIT is used worldwide, there are still gaps and limitations, including the lack of reliable biomarkers predictive of the clinical outcome. Novel adjuvants are currently under investigations to boost the strength and efficiency of the immune response, as well as new formulations with better efficacy and better patient's adherence to the treatment. Herein, we aim to provide an overview of current key evidence with major regard to clinical practice as well as knowledge gaps and future research needs in the context of AIT in children with respiratory allergic diseases.


Assuntos
Asma/prevenção & controle , Conjuntivite Alérgica/prevenção & controle , Dessensibilização Imunológica/métodos , Cooperação do Paciente , Rinite Alérgica/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Administração Sublingual , Fatores Etários , Asma/imunologia , Criança , Pré-Escolar , Dessensibilização Imunológica/história , História do Século XX , História do Século XXI , Humanos , Imunidade Celular , Imunoglobulina E/imunologia , Injeções Subcutâneas , Rinite Alérgica/imunologia , Fatores de Tempo
8.
Breastfeed Med ; 14(7): 493-498, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31368780

RESUMO

Background/Objective: Performance of ocular examinations on children who were breastfed, fed with formula, and combination of the two for the first 6 months of age. Subsequently, refractive errors, allergic conjunctivitis, and retinal nerve fiber layer (RNFL) thickness were evaluated. Materials and Methods: The present study included a total of 242 eyes of 121 children (aged 60-84 months, 65 males, 56 females) admitted to the outpatient clinic of our institution. The patients were divided into three groups according to their feeding pattern during their first 6 months postdelivery: breastfed children (Group 1, n = 40), children fed with a combination of breast and formula milk (Group 2, n = 41), and children exclusively fed with formula-milk (Group 3, n = 40). All patients underwent detailed ophthalmologic examinations, and measurements of the RNFLs were recorded. Results: No significant difference was observed between the groups in terms of refractive error. In Group 3, we found that allergic conjunctivitis was significantly higher than in the other groups. In addition, in Group 3, the thickness of the RNFL was found to be significantly higher in the superior quadrants of both the eyes of children than in Groups 1 and 2 (p < 0.05). Conclusions: We found that the type of feeding experienced by infants in their first 6 months has no effect on refractive error but has significant effects on both allergic conjunctivitis and RNFL. To determine the cause of this difference in the RNFL and to further validate the present study, future studies with larger patient groups and animal experiments are needed.


Assuntos
Aleitamento Materno , Conjuntivite Alérgica/imunologia , Olho/anatomia & histologia , Fórmulas Infantis , Leite Humano/imunologia , Acuidade Visual/fisiologia , Criança , Pré-Escolar , Conjuntivite Alérgica/prevenção & controle , Estudos Transversais , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Estudos Prospectivos , Acuidade Visual/imunologia
9.
Ocul Immunol Inflamm ; 27(4): 622-631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29543548

RESUMO

Purpose: To compare alcaftadine and olopatadine ophthalmic solutions, and vehicle for preventing allergen-mediated conjunctivitis in Japanese subjects. Methods: Japanese cedar pollen-sensitive subjects were randomized to alcaftadine 0.25%, olopatadine 0.1%, or vehicle. Ocular itching was assessed at 3, 5 (primary outcome), 7, and 15 min post-conjunctival allergen challenge (CAC) and conjunctival hyperemia assessed at 7, 15 (secondary outcome), and 20 min post-CAC. Adverse events were monitored. Results: Overall, 240 subjects were randomized. Alcaftadine 0.25% (challenged 8 h post-dose) was significantly more effective than vehicle for prevention of itching and conjunctival hyperemia (p < 0.001) and noninferior to olopatadine 0.1% (challenged 4 h post-dose). Significantly lower hyperemia scores were observed in alcaftadine-treated than olopatadine-treated eyes at 7 and 15 min post-CAC (p ≤ 0.027). Alcaftadine and olopatadine were well tolerated; no serious adverse events were reported. Conclusion: Alcaftadine 0.25% is effective in preventing signs and symptoms of Japanese cedar pollen-induced allergic conjunctivitis.


Assuntos
Benzazepinas/administração & dosagem , Cedrus/efeitos adversos , Conjuntivite Alérgica/prevenção & controle , Imidazóis/administração & dosagem , Cloridrato de Olopatadina/administração & dosagem , Pólen/efeitos adversos , Adulto , Conjuntivite Alérgica/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Incidência , Japão/epidemiologia , Masculino , Soluções Oftálmicas/administração & dosagem , Estudos Retrospectivos , Estações do Ano , Resultado do Tratamento
10.
Eur Arch Otorhinolaryngol ; 276(3): 729-734, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30554359

RESUMO

PROPOSE: Allergic rhinitis (AR) is a very common, chronic and global health problem. In the last two decades, the efficiency of barrier-enforcing measures in AR has been investigated. In this study, we aimed to evaluate the effect of allergen-blocker mechanical barrier gel (MBG) (AlerjiSTOP®) treatment on symptoms and quality of life score (QoLS) in patients with seasonal and perennial allergic rhinitis. METHODS: A single-center, prospective study was conducted between January 2017 and May 2018. Patients diagnosed with allergic rhinitis with a visual analogue scale (VAS) of 5 or higher (moderate/severe) were enrolled in the study. Patients were evaluated in terms of VAS, nasal symptom score (NSS), ocular symptom score (OSS), total symptom score (TSS) and QoLS at baseline, 1 week and 1 month of MBG treatment. RESULTS: A total of 83 patients with AR were enrolled in the study. Clinical and laboratory examinations showed that 50 (60.2%) patients were mono-sensitized. Allergen-blocker mechanical barrier gel treatment was performed as monotherapy in 22 (26.5%) patients. Median VAS, NSS, OSS and TSS decreased from 7 to 4, 8 to 3, 4 to 0 and 12 to 4, respectively (p < 0.0001). Correlation analysis revealed positive correlations between lower pediatric rhinoconjunctivitis quality of life questionnaire scores for patients under 12 years of age and decrease in VAS, NSS and TSS (r = 0.380, p = 0.008; r = 0.544, p < 0.0001; r = 0.543, p < 0.0001). Positive correlations were detected between lower rhinoconjunctivitis quality of life questionnaire (self-administered) scores for patients ≥ 12 years of age and decrease in VAS, NSS, OSS and TSS (r = 0.703, p < 0.0001; r = 0.465, p = 0.005; r = 0.526, p = 0.001; r = 0.624, p < 0.0001). CONCLUSION: In conclusion, we found significant decrease in all symptom scores and improvement in QoLS of patients treated with MBG as monotherapy and combination therapy.


Assuntos
Alérgenos , Conjuntivite Alérgica/prevenção & controle , Géis/administração & dosagem , Qualidade de Vida , Rinite Alérgica Perene/prevenção & controle , Rinite Alérgica Sazonal/prevenção & controle , Administração Intranasal , Adolescente , Criança , Conjuntivite Alérgica/diagnóstico , Feminino , Humanos , Masculino , Nariz , Estudos Prospectivos , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Sazonal/diagnóstico , Inquéritos e Questionários , Escala Visual Analógica
11.
Clin Immunol ; 190: 1-10, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29432811

RESUMO

Allergic conjunctivitis is mediated by eosinophilic infiltration and Th2 type immune responses. This study aims to elucidate the role of rapamycin, mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC). Rapamycin administration intraperitoneally markedly reduced clinical signs, total and OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were attenuated in rapamycin-treated mice, as well as decreased Th1 and Th2 cytokines in the cervical lymph nodes compared to non-treated mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin. These findings suggest the therapeutic implications of rapamycin in the attenuation of allergic conjunctivitis.


Assuntos
Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/prevenção & controle , Sirolimo/farmacologia , Células Th2/imunologia , Animais , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/metabolismo , Conjuntivite Alérgica/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunossupressores/farmacologia , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia
12.
Allergy ; 73(4): 765-798, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28940458

RESUMO

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.


Assuntos
Conjuntivite Alérgica/prevenção & controle , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/normas , Rinite Alérgica/prevenção & controle , Humanos
13.
Ocul Immunol Inflamm ; 26(3): 440-448, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27726468

RESUMO

PURPOSE: To determine the immunologic functions of TRPA1 or TRPV1 in allergic conjunctivitis (AC). METHODS: Mice were sensitized with ovalbumin (OVA), after which TRPA1 antagonist or TRPV1 antagonist was administered before topical OVA challenge. Expression of TRPV1 or TRPA1 in AC was examined by western blotting and multicolor immunofluorescence. Clinical signs, OVA-specific IgE, infiltration of inflammatory cells into conjunctivae (CJs), and Th2 cytokine in draining lymph nodes (LNs) were evaluated by microscopy, flow cytometry, and ELISA. RESULTS: TRPV1 expression was increased in CJs and LNs from AC mice, but TRPA1 expression was only increased in LNs. TRPV1 antagonist but not TRPA1 antagonist attenuated the clinical signs of AC and OVA-specific IgE in sera. TRPV1 antagonist furthermore inhibited the infiltration of inflammatory cells into CJ and the production of Th2 cytokines in LNs. CONCLUSION: TRPV1 antagonist but not TRPA1 antagonist may ameliorate AC by suppressing the Th2 response in LNs.


Assuntos
Capsaicina/análogos & derivados , Conjuntivite Alérgica/prevenção & controle , Modelos Animais de Doenças , Canais de Cátion TRPV/antagonistas & inibidores , Acetanilidas/uso terapêutico , Animais , Western Blotting , Capsaicina/uso terapêutico , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/patologia , Ensaio de Imunoadsorção Enzimática , Eosinófilos/patologia , Técnica Indireta de Fluorescência para Anticorpo , Imunoglobulina E/sangue , Masculino , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Purinas/uso terapêutico , Canal de Cátion TRPA1/antagonistas & inibidores
14.
Allergy ; 73(5): 1101-1109, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29159975

RESUMO

BACKGROUND: The Global Allergy and Asthma European Network (GA2 LEN) Taskforce has requested more data on correlations between various patient-reported outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis. METHODS: In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated. RESULTS: Upon comparing RCAT and RQLQ results, we found strong correlations of r = -0.871 for grass pollen-allergic patients and r = -0.795 for birch pollen-allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = -0.811 (grass pollen-allergic patients) and a moderate correlation of r = -0.539 (birch pollen-allergic patients). In the RCAT, 69.7% of grass pollen-allergic patients and 45.7% of birch pollen-allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms. CONCLUSION: The strong correlations suggest that the RCAT alone is equivalent to the RQLQ with respect to patients' symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.


Assuntos
Conjuntivite Alérgica/prevenção & controle , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Rinite Alérgica Sazonal/prevenção & controle , Rinite Alérgica/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imunoterapia Sublingual , Inquéritos e Questionários
15.
Allergy ; 73(4): 896-904, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29150857

RESUMO

BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 µg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. RESULTS: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 µg; P = .023), 46.3% (370 µg), and 38.6% (70 µg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-µg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 µg: 17.1%; 170 µg: 18.8%; 370 µg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 µg), 3.1-fold (170 µg) and 3.9-fold (370 µg) (mPP). CONCLUSION: Three-week immunotherapy with 170 µg LPP reduced CPT reactivity significantly and increased protective specific antibodies.


Assuntos
Conjuntivite Alérgica/prevenção & controle , Dessensibilização Imunológica/métodos , Rinite Alérgica Sazonal/prevenção & controle , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Lolium , Masculino , Peptídeos/administração & dosagem , Peptídeos/imunologia
16.
Allergy ; 73(1): 187-195, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28675499

RESUMO

BACKGROUND: A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters. METHODS: This two-arm study included patients aged ≥12 years with recurrent grass pollen-induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL® ); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients' state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed. RESULTS: The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P<.01). Moreover, significantly more patients in this group used no concomitant antiallergic medication throughout the peak grass pollen season. Twice as many patients in the booster AIT group as in the control group reported having a better state of health than in the preceding season. MiniRQLQ results showed significant differences favouring the booster AIT. The booster AIT was generally well tolerated, with only two patients reporting mild, grade 1 systemic adverse events. CONCLUSION: Booster AIT using tyrosine-absorbed allergoids containing the adjuvant MPL® effectively prevents re-occurrence of symptoms in patients with grass pollen-induced ARC.


Assuntos
Alérgenos/imunologia , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/prevenção & controle , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Adulto , Antígenos de Plantas , Dessensibilização Imunológica , Feminino , Humanos , Imunização Secundária , Masculino , Pessoa de Meia-Idade
17.
Graefes Arch Clin Exp Ophthalmol ; 255(12): 2357-2362, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28840310

RESUMO

PURPOSE: Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis. METHODS: The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used. In the OA model, an Evans Blue stain concentration of conjunctival tissue was used to evaluate vascular leakage due to allergic reaction. RESULTS: The cis-UCA was well tolerated and effective in both the IgE-independent and -mediated rat models. Treatment with C48/80 caused conjunctival hyperaemia, which was significantly inhibited by ketotifen at the 6 h time point (p = 0.014) and by dexamethasone and cis-UCA 0.5% at 12 (p = 0.004) and 24 (p = 0.004) hour time points. In a comparison between the active drug treatments, only ketotifen showed a significant difference (p = 0.023) to cis-UCA treatment at the 1 h time point, otherwise there were no statistically significant differences between the active drugs. Ketotifen, dexamethasone and cis-UCA 0.5% significantly inhibited the C48/80-induced nuclear accumulation of Ki-67, without differences between the active treatment groups. In the OA model, cis-UCA 0.5% did not inhibit the vascular leakage of conjunctiva, whereas cis-UCA 2.5% of was at least equally effective compared to olopatadine, abolishing the allergic vascular leakage response almost completely. CONCLUSIONS: The present findings in the two AC models suggest that cis-UCA might have anti-allergic potency both in immediate and delayed-type allergic reactions in the eye.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Conjuntivite Alérgica/prevenção & controle , Imunoglobulina E/imunologia , Ácidos Oleicos/administração & dosagem , Administração Tópica , Animais , Conjuntivite Alérgica/induzido quimicamente , Conjuntivite Alérgica/imunologia , Modelos Animais de Doenças , Soluções Oftálmicas , Ratos , Ratos Sprague-Dawley , Ratos Wistar , p-Metoxi-N-metilfenetilamina/toxicidade
19.
BMC Ophthalmol ; 16(1): 190, 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27793114

RESUMO

BACKGROUND: Ocular allergy is a growing public health problem that greatly impacts the day-to-day life of sufferers and their families. Other aspects of their activities of daily living such as schooling, professional, and social life are affected hence an increased awareness and knowledge of ocular allergies, their detection and treatment is paramount. This study was to assess the level of knowledge and awareness of ocular allergy among undergraduate students of public universities in Ghana. METHODS: A descriptive cross sectional survey was conducted among 1000 students from three selected public universities in Ghana. Each respondent completed a questionnaire that had questions concerning awareness and knowledge of ocular allergy. RESULTS: Out of the 1000 students, 347 (34.7 %) were aware of ocular allergy. Of these 347 students, the level of knowledge of ocular allergy was generally low. Majority of the students had their source of information about ocular allergy from the media and the internet. There was statistical significant association among awareness of ocular allergy, sources of information and programme of study (p < 0.001). CONCLUSION: Level of awareness among university students is generally low. Students' programmes of study influenced their knowledge of ocular allergy. Public health measures are recommended to help educate students on the prevention and control of ocular allergy as well as the complications associated with this condition.


Assuntos
Conjuntivite Alérgica , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Conscientização , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/etiologia , Conjuntivite Alérgica/prevenção & controle , Estudos Transversais , Infecções Oculares/complicações , Feminino , Gana , Humanos , Masculino , Estudantes , Adulto Jovem
20.
J Allergy Clin Immunol ; 138(2): 367-374.e2, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27260321

RESUMO

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.


Assuntos
Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Adolescente , Adulto , Fatores Etários , Algoritmos , Tomada de Decisão Clínica , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/prevenção & controle , Conjuntivite Alérgica/terapia , Gerenciamento Clínico , Humanos , Satisfação do Paciente , Rinite Alérgica/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...