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1.
São Paulo; s.n; 2023. 25 p.
Tese em Português | Coleciona SUS, Sec. Munic. Saúde SP, HSPM-Producao, Sec. Munic. Saúde SP | ID: biblio-1531258

RESUMO

A Síndrome de Kounis é uma condição que se manifesta como uma síndrome coronária aguda (SCA) em um contexto de reação de hipersensibilidade a diversos alérgenos. O mecanismo fisiopatológico central desta síndrome está associado ao vasoespasmo coronário. No caso, trata-se de um paciente com dor abdominal inespecífica que durante a administração da escopolamina, desenvolveu sintomas indicativos de síndrome coronária aguda, sem elevação do segmento ST no eletrocardiograma, porém com aumento da troponina ultrassensível. O paciente foi submetido a estratificação não invasiva para SCA, que não demonstrou doença coronária. Palavras-chave: Síndrome de Kounis. Vasoespasmo coronário. Dor no peito. Hipersensibilidade a Drogas. Escopolamina.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Escopolamina/efeitos adversos , Dor no Peito/diagnóstico , Alérgenos/efeitos dos fármacos , Síndrome Coronariana Aguda , Síndrome de Kounis/diagnóstico
2.
Clin Transl Sci ; 14(6): 2440-2449, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34437752

RESUMO

REGN1908-1909, a 1:1 cocktail of two fully human IgG4 monoclonal antibodies (mAbs), REGN1908 and REGN1909, is being evaluated for treatment of cat allergy. Both REGN1908 and REGN1909 bind to the dominant cat allergen, Fel d 1. Adults with cat allergy confirmed by skin prick test (SPT) were randomized to single subcutaneous administration of placebo (n = 6) or REGN1908-1909 at doses of 150 (n = 6), 300 (n = 6), or 600 mg (n = 6). Blood samples were taken at prespecified time points for pharmacokinetic (PK) analysis and exploratory evaluation of biomarkers (IgE and SPT). Safety was assessed. Drug concentration-time profiles in serum for ascending doses of REGN1908-1909 were consistent with linear PKs. Noncompartmental analysis showed that maximum concentration (Cmax ) and exposure increased proportionately with dose, with similar time to maximum concentration (Tmax ) for REGN1908 and REGN1909 (6.2 to 8.2 days across doses), and a longer terminal half-life for REGN1908 (~ 30 days) relative to REGN1909 (~ 21 days). Adverse events were not dose dependent; there were no dose-limiting toxicities. REGN1908-1909 is characterized by linear and dose-proportional kinetics of the two individual mAb components. A single 600 mg dose maintains total mAb mean concentrations in serum above the target (mean of ~ 10 mg/L) for 8-12 weeks. Maintaining this mean target concentration resulted in translational pharmacodynamic effects: maximal mast cell degranulation in a passive cutaneous anaphylaxis mouse model, and maintenance of clinical efficacy measured by Total Nasal Symptom Score in a previous proof-of-mechanism study.


Assuntos
Alérgenos/efeitos dos fármacos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/farmacocinética , Hipersensibilidade/tratamento farmacológico , Adolescente , Adulto , Alérgenos/imunologia , Animais , Antialérgicos/farmacologia , Antialérgicos/uso terapêutico , Anticorpos Monoclonais/imunologia , Gatos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Allergol. immunopatol ; 49(2): 129-132, mar. 2021. tab
Artigo em Inglês | IBECS | ID: ibc-214251

RESUMO

Routine diagnostic methods for allergies to plant-derived foods are based on skin prick test (SPT) with commercial extracts, prick-by-prick (PbP) with fresh food, serum-specific IgE measurement, and oral food challenge. We discuss the possibility and the advantages of performing, in patients with oral allergy syndrome (OAS) by fruit and vegetables (excluding nuts) PR-10 allergy, component-resolved diagnosis (CRD) by SPT and PbP with raw and cooked vegetables, rather than performing a CRD with in vitro tests by drawing blood. Based on our clinical experience and the studies published in the literature, we believe that, at least for the OAS by fruit and vegetables (excluding nuts) PR-10 allergy, the search for sensitizing allergens and related cross-reactive allergens with SPT and PbP can be performed routinely in clinical practice, even at the primary-care level (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Alérgenos/efeitos dos fármacos , Hipersensibilidade Alimentar/diagnóstico , Frutas/efeitos adversos , Proteínas de Vegetais Comestíveis/efeitos adversos , Alérgenos/administração & dosagem , Alérgenos/imunologia , Reações Cruzadas , Hipersensibilidade Alimentar/imunologia , Frutas/imunologia , Proteínas de Vegetais Comestíveis/imunologia , Testes Cutâneos
4.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L693-L709, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783616

RESUMO

Many mouse models of allergic asthma exhibit eosinophil-predominant cellularity rather than the mixed-granulocytic cytology in steroid-unresponsive severe disease. Therefore, we sought to implement a novel mouse model of antigen-driven, mixed-granulocytic, severe allergic asthma to determine biomarkers of the disease process and potential therapeutic targets. C57BL/6J wild-type, interleukin-6 knockout (IL-6-/-), and IL-6 receptor knockout (IL-6R-/-), mice were injected with an emulsion of complete Freund's adjuvant and house dust mite antigen (CFA/HDM) on day 1. Dexamethasone, a lymphocyte-depleting biological, or anti-IL-17A was administered during the intranasal HDM challenge on days 19-22. On day 23, the CFA/HDM model elicited mixed bronchoalveolar lavage (BAL) cellularity (typically 80% neutrophils and 10% eosinophils), airway hyperresponsiveness (AHR) to methacholine, diffusion impairment, lung damage, body weight loss, corticosteroid resistance, and elevated levels of serum amyloid A (SAA), pro-inflammatory cytokines, and T helper type 1/ T helper type 17 (Th1/Th17) cytokines compared with eosinophilic models of HDM-driven allergic airway disease. BAL cells in IL-6- or IL-6R-deficient mice were predominantly eosinophilic and associated with elevated T helper type 2 (Th2) and reduced Th1/Th17 cytokine production, along with an absence of SAA. Nevertheless, AHR remained in IL-6-deficient mice even when dexamethasone was administered. However, combined administration of anti-IL-17A and systemic corticosteroid significantly attenuated both overall and neutrophilic airway inflammation and also reduced AHR and body weight loss. Inhibition of IL-17A combined with systemic corticosteroid treatment during antigen-driven exacerbations may provide a novel therapeutic approach to prevent the pathological pulmonary and constitutional changes that greatly impact patients with the mixed-granulocytic endotype of severe asthma.


Assuntos
Corticosteroides/farmacologia , Asma/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Alérgenos/efeitos dos fármacos , Alérgenos/imunologia , Animais , Asma/patologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Hipersensibilidade Respiratória/patologia , Células Th17/imunologia
5.
Front Immunol ; 10: 2212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616416

RESUMO

Extracellular host-derived DNA, as one of damage associated molecular patterns (DAMPs), is associated with allergic type 2 immune responses. Immune recognition of such DNA generates the second messenger cyclic GMP-AMP (cGAMP) and induces type-2 immune responses; however, its role in allergic diseases, such as asthma, has not been fully elucidated. This study aimed to determine whether cGAMP could induce asthma when used as an adjuvant. We intranasally sensitized mice with cGAMP together with house dust mite antigen (HDM), followed by airway challenge with HDM. We then assessed the levels of eosinophils in the broncho-alveolar lavage fluid (BALF) and serum HDM-specific antibodies. cGAMP promoted HDM specific allergic asthma, characterized by significantly increased HDM specific IgG1 and total IgE in the serum and infiltration of eosinophils in the BALF. cGAMP stimulated lung fibroblast cells to produce IL-33 in vitro, and mice deficient for IL-33 or IL-33 receptor (ST2) failed to develop asthma enhancement by cGAMP. Not only Il-33-/- mice, but also Sting-/-, Tbk1-/-, and Irf3-/-Irf7-/- mice which lack the cGAMP-mediated innate immune activation failed to increase eosinophils in the BALF than that from wild type mice. Consistently, intranasal and oral administration of amlexanox, a TBK1 inhibitor, decreased cGAMP-induced lung allergic inflammation. Thus, cGAMP functions as a type 2 adjuvant in the lung and can promote allergic asthma in manners that dependent on the intracellular STING/TBK1/IRF3/7 signaling pathway and the resultant intercellular signaling pathway via IL-33 and ST2 might be a novel therapeutic target for allergic asthma.


Assuntos
Aminopiridinas/farmacologia , Asma/tratamento farmacológico , Asma/imunologia , Interleucina-33/imunologia , Nucleotídeos Cíclicos/imunologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/imunologia , Alérgenos/efeitos dos fármacos , Alérgenos/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Eosinofilia Pulmonar/tratamento farmacológico , Eosinofilia Pulmonar/imunologia , Pyroglyphidae/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia
6.
Plant Physiol Biochem ; 135: 331-340, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30599310

RESUMO

In the present work, for the first time in the literature, the relationship between the degree of air pollution, the physiological state of the plants and the allergenic capacity of the pollen they produce has been studied. The physiological state of Lolium perenne plants growing in two cities with a high degree of traffic, but with different levels of air pollution, Madrid and Ciudad Real, have been explored. The photosynthetic efficiency of the plants through the emission of fluorescence of PSII, the degree of oxidative stress (enzymatic activities related to the ascorbate-glutathione cycle), the redox state (reduced and oxidized forms of ascorbate and glutathione) and the concentration of malondialdehyde have been evaluated. During the development period of the plants, Madrid had higher levels of NO2 and SO2 than Ciudad Real. The greater degree of air pollution suffered by Madrid plants was reflected on a lower photosynthetic efficiency and a greater degree of oxidative stress. In addition, NADPH oxidase activity and H2O2 levels in pollen from Madrid were significantly higher, suggesting a likely higher allergenic capacity of this pollen associated to a higher air pollution.


Assuntos
Poluentes Atmosféricos/farmacologia , Alérgenos/imunologia , Lolium/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pólen/imunologia , Poluição do Ar/efeitos adversos , Alérgenos/efeitos dos fármacos , Ácido Ascórbico/metabolismo , Clorofila/metabolismo , Glutationa/metabolismo , Lolium/imunologia , Lolium/metabolismo , Malondialdeído/metabolismo , Fotossíntese/efeitos dos fármacos , Pólen/efeitos dos fármacos
7.
Environ Sci Pollut Res Int ; 25(1): 469-478, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29043591

RESUMO

The saprotrophic fungus Alternaria alternata is widespread in the agro-environment and produces more than ten allergenic proteins, mostly protein Alt a 1. The frequency of the Alt a 1 gene was analyzed in a group of A. alternata isolates from winter wheat kernels obtained in Poland, and the effectiveness of various fungicides targeting the pathogen was evaluated. The Alt a 1 gene was identified in four of the seven tested isolates. A. alternata colonized 35.67% kernels on average, but its frequency increased in stored grain where the presence of epiphytes was noted on 23.09 to 51.38% kernels, and endophytes-in 26.21 to 42.01% of kernels. The efficacy of field-applied fungicides did not exceed 50%, despite the fact that A. alternata is highly sensitive to propiconazole, fenpropimorph, and tebuconazole under in vitro conditions. The analyzed isolates were characterized by limited sensitivity to azoxystrobin (EC50 ranged from 0.505 to 1.350 µg cm-3) due to a mutation at codon 143 of the CYT b gene, responsible for resistance to quinone outside inhibitor fungicides, which was noted in all isolates. The spread of A. alternata can be effectively controlled with suitable fungicides and by monitoring the prevalence of pathogenic isolates in the environment.


Assuntos
Alérgenos/genética , Alternaria/genética , Citocromos b/genética , Fungicidas Industriais/farmacologia , Mutação , Pirimidinas/farmacologia , Estrobilurinas/farmacologia , Alérgenos/efeitos dos fármacos , Alérgenos/isolamento & purificação , Alternaria/efeitos dos fármacos , Alternaria/isolamento & purificação , Farmacorresistência Fúngica , Polônia , Triticum/microbiologia
8.
J Sci Food Agric ; 96(12): 4263-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26800007

RESUMO

BACKGROUND: Malonaldehyde, the primary by-product of lipid peroxidation in food, modifies the structural and functional properties of proteins by cross-linking. The aim of this study was to investigate the effect of malonaldehyde on the allergenicity of shrimp tropomyosin. RESULTS: RBL-2H3 cells, a model of type I allergic reactions, were sensitised with sera from patients allergic to shrimp, and were stimulated with native and cross-linked tropomyosin. Release of inflammatory mediators such as ß-hexosaminidase, histamine, tryptase, cysteinyl leukotriene, and prostaglandin D2 was clearly suppressed in a manner that depended on the extent of tropomyosin cross-linking. Release of interleukin-4 (IL-4) and IL-13 was similarly decreased. Notably, cells sensitised with one patient's serum released IL-4 at comparable levels in response to native and cross-linked tropomyosin. CONCLUSION: Cross-linking strongly modulates the ability of shrimp tropomyosin to induce release of inflammatory cytokines and mediators from activated RBL-2H3 cells. © 2016 Society of Chemical Industry.


Assuntos
Alérgenos/efeitos dos fármacos , Reagentes de Ligações Cruzadas/farmacologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Malondialdeído/farmacologia , Tropomiosina/farmacologia , Animais , Linhagem Celular , Citocinas/imunologia , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/imunologia , Humanos , Mediadores da Inflamação/imunologia , Penaeidae/química , Penaeidae/imunologia , Ratos , Tropomiosina/imunologia
9.
Int Forum Allergy Rhinol ; 6(1): 95-100, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26332319

RESUMO

BACKGROUND: Nitrogen dioxide (NO2) and sulfur dioxide (SO2) generated by excessive coal combustion and motor vehicle emissions are major air pollutants in the large cities of China. The objective of our study was to determine the effects of the exposure of oak pollens (Quercusmongolica) to several concentrations of NO2 or SO2. METHODS: Pollen grains were exposed to 0.5 ppm to 5.0 ppm NO2 or SO2 for 4 hours and assessed for morphological damage by field emission scanning electron microscopy and for viability using the trypan blue stain. Morphological changes in pollen grains were also examined after contact with acid solutions at pH 4.0 to pH 7.0. RESULTS: Exposure to NO2 or SO2 significantly damaged pollen grains at all concentrations investigated, compared to exposure to air; with exposure to concentrations of 0.5 ppm to 2 ppm resulting in fissures or complete breaks in the exine and a concentration of 5 ppm resulting in complete breakdown and release of pollen cytoplasmic granules. Significantly greater amounts of pollen grain were damaged after exposure to SO2 (15.5-20.4%) than after exposure to NO2 (7.1-14.7%). Similarly, exposure to NO2 or SO2 significantly decreased the viability of pollen grains, compared with exposure to air; with SO2 being slightly more detrimental than NO2. Exposure to acid solutions also induced pollen damage, which appeared to be pH-dependent (from 24.6% at pH 6.0 to 55.8% at pH 4.0; compared to 3.8% at pH 7.0). CONCLUSION: Short-term exposure of oak pollen to high concentrations of SO2 or NO2 significantly increases their fragility and disruption, leading to subsequent release of pollen cytoplasmic granules into the atmosphere. These results suggest that heightened air pollution during the oak pollen season may possibly increase the incidence of allergic airway disease in sensitized individuals by facilitating the bioavailability of airborne pollen allergens.


Assuntos
Poluentes Atmosféricos/toxicidade , Alérgenos/efeitos dos fármacos , Dióxido de Nitrogênio/toxicidade , Pólen/efeitos dos fármacos , Quercus/efeitos dos fármacos , Dióxido de Enxofre/toxicidade , Alérgenos/fisiologia , Sobrevivência Celular , China , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/fisiologia , Pólen/anatomia & histologia , Pólen/fisiologia , Quercus/anatomia & histologia , Quercus/fisiologia
10.
Plant Cell Environ ; 39(1): 147-64, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26177592

RESUMO

Ragweed pollen is the main cause of allergenic diseases in Northern America, and the weed has become a spreading neophyte in Europe. Climate change and air pollution are speculated to affect the allergenic potential of pollen. The objective of this study was to investigate the effects of NO2 , a major air pollutant, under controlled conditions, on the allergenicity of ragweed pollen. Ragweed was exposed to different levels of NO2 throughout the entire growing season, and its pollen further analysed. Spectroscopic analysis showed increased outer cell wall polymers and decreased amounts of pectin. Proteome studies using two-dimensional difference gel electrophoresis and liquid chromatography-tandem mass spectrometry indicated increased amounts of several Amb a 1 isoforms and of another allergen with great homology to enolase Hev b 9 from rubber tree. Analysis of protein S-nitrosylation identified nitrosylated proteins in pollen from both conditions, including Amb a 1 isoforms. However, elevated NO2 significantly enhanced the overall nitrosylation. Finally, we demonstrated increased overall pollen allergenicity by immunoblotting using ragweed antisera, showing a significantly higher allergenicity for Amb a 1. The data highlight a direct influence of elevated NO2 on the increased allergenicity of ragweed pollen and a direct correlation with an increased risk for human health.


Assuntos
Alérgenos/imunologia , Ambrosia/imunologia , Antígenos de Plantas/imunologia , Dióxido de Nitrogênio/farmacologia , Extratos Vegetais/imunologia , Poluição do Ar , Alérgenos/efeitos dos fármacos , Alérgenos/genética , Ambrosia/efeitos dos fármacos , Ambrosia/genética , Antígenos de Plantas/efeitos dos fármacos , Antígenos de Plantas/genética , Mudança Climática , Análise por Conglomerados , Eletroforese em Gel Bidimensional , Europa (Continente) , Humanos , Extratos Vegetais/genética , Proteínas de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Estações do Ano
11.
Ann Am Thorac Soc ; 12 Suppl 2: S133-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26595728

RESUMO

In asthma, reactive oxygen species induce damage to biomolecules like proteins. This oxidative stress can promote inflammation, but its contribution to asthma pathology is controversial, not in the least because antioxidant interventions have proven rather unsuccessful. Recent studies indicate that the oxidative stress at baseline can be predictive of the fall in FEV1 upon an allergen challenge and of sensitization to an allergen. Interestingly, this baseline oxidative stress correlated with the capacity of antioxidant and cytoprotective responses to deal with reactive oxygen species, but not with inflammatory parameters. These findings have led to several considerations in relation to antioxidant trials that are discussed. Trials should be complemented by in-depth analyses of the failing antioxidant and cytoprotective responses and their consequences for cellular function in asthma.


Assuntos
Antioxidantes/uso terapêutico , Asma/imunologia , Hipersensibilidade/imunologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/imunologia , Alérgenos/efeitos dos fármacos , Progressão da Doença , Humanos , Inflamação/imunologia
12.
Allergy ; 70(8): 897-909, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25913519

RESUMO

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with ß-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.


Assuntos
Alérgenos/imunologia , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade/tratamento farmacológico , Administração Sublingual , Alérgenos/efeitos dos fármacos , Antialérgicos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Consenso , Medicina Baseada em Evidências , Feminino , Humanos , Hipersensibilidade/imunologia , Injeções Subcutâneas , Masculino , Segurança do Paciente , Medição de Risco , Resultado do Tratamento
13.
Am J Respir Crit Care Med ; 191(2): 161-7, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25473939

RESUMO

RATIONALE: Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids. OBJECTIVES: We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses. METHODS: Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 µg) once daily, budesonide 200 µg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study. Allergen challenge was performed on Day 6. MEASUREMENTS AND MAIN RESULTS: FEV1 was measured repeatedly for 7 hours after allergen challenge for early and late asthmatic responses. Sputum inflammatory cells was measured before and at 7 and 24 hours after allergen challenge, and methacholine airway responsiveness was measured before and 24 hours after allergen challenge. AZD5423 significantly attenuated the fall in FEV1 during the late asthmatic response (both doses led to an 8.7% fall) versus placebo (14% fall) (P < 0.05) with no effect of budesonide (12.5% fall) versus placebo (P > 0.05). There was no effect on the fall in FEV1 during early asthmatic response. AZD5423 300 and 75 µg significantly attenuated allergen-induced sputum eosinophilia by 63 and 61% at 7 hours, respectively, and by 46 and 34% at 24 hours after allergen challenge, respectively, versus placebo (all P < 0.05). Budesonide did not reduce allergen-induced sputum eosinophilia versus placebo. AZD5423 at 300 µg significantly attenuated allergen-induced airway hyperresponsiveness at 24 hours after allergen challenge versus placebo (P < 0.05). Both doses of AZD5423 were well tolerated. CONCLUSIONS: Seven-day treatment with inhalation of the nonsteroidal glucocorticoid receptor agonist AZD5423 effectively reduced allergen-induced responses in subjects with mild allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01225549).


Assuntos
Alérgenos/efeitos dos fármacos , Antiasmáticos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Asma/tratamento farmacológico , Receptores de Glucocorticoides/agonistas , Administração por Inalação , Adolescente , Adulto , Alérgenos/fisiologia , Antiasmáticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos Cross-Over , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Glucocorticoides/administração & dosagem , Receptores de Glucocorticoides/uso terapêutico , Escarro/citologia , Adulto Jovem
14.
Peptides ; 62: 144-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25281794

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease with heterogeneous clinical phenotypes reflecting genetic predisposition and exposure to environmental factors. Reactions to food may play a significant role especially in young children. Milk proteins are particularly strong allergens and are additional source of bioactive peptides including ß-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile). BCM7 exerts its influence on nervous, digestive, and immune functions via the µ-opioid receptor (MOR). Proline dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) appears to be the primary degrading enzyme of BCM7. Moreover, DPPIV is known to restrict activity of proinflammatory peptides. BCM7 is considered to modulate an immune response by affecting MOR and DPPIV genes expression. In this study, we determined the MOR and DPPIV genes expression in children diagnosed with a severe form of AD. 40 healthy children and 62 children diagnosed with severe AD (AD score ≥60) were included in the study. Peripheral blood mononuclear cells (PBMCs) from the studied subjects were incubated with the peptide extracts of raw and hydrolysed cow milk with defined ß-casein genotypes (A1A1, A2A2 and A1A2) and MOR and DPPIV genes expression was determined with real-time PCR. Incubation PBMCs with peptide extracts from cow milk caused an increase of the MOR gene expression (p<0.05; p<0.001) in AD children with a simultaneous decrease in the DPPIV gene expression (p<0.001). The obtained results supplement the knowledge on the BCM7 participation in AD etiology and provide an important diagnostic tool.


Assuntos
Dermatite Atópica/tratamento farmacológico , Endorfinas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Hipersensibilidade a Leite/tratamento farmacológico , Fragmentos de Peptídeos/administração & dosagem , Adolescente , Alérgenos/efeitos dos fármacos , Animais , Bovinos , Criança , Dermatite Atópica/genética , Dermatite Atópica/patologia , Dipeptidil Peptidase 4/biossíntese , Endorfinas/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Hipersensibilidade a Leite/genética , Hipersensibilidade a Leite/patologia , Proteínas do Leite/efeitos adversos , Fragmentos de Peptídeos/metabolismo , Receptores Opioides mu/biossíntese
15.
J Agric Food Chem ; 62(28): 6746-55, 2014 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-24926808

RESUMO

Cashew nut and other nut allergies can result in serious and sometimes life-threatening reactions. Linear and conformational epitopes within food allergens are important for immunoglobulin E (IgE) binding. Methods that disrupt allergen structure can lower IgE binding and lessen the likelihood of food allergy reactions. Previous structural and biochemical data have indicated that 2S albumins from tree nuts and peanuts are potent allergens, and that their structures are sensitive to strong reducing agents such as dithiothreitol. This study demonstrates that the generally regarded as safe (GRAS) compound sodium sulfite effectively disrupted the structure of the cashew 2S albumin, Ana o 3, in a temperature-dependent manner. This study also showed that sulfite is effective at disrupting the disulfide bond within the cashew legumin, Ana o 2. Immunoblotting and ELISA demonstrated that the binding of cashew proteins by rabbit IgG or IgE from cashew-allergic patients was markedly lowered following treatment with sodium sulfite and heating. The results indicate that incorporation of sodium sulfite, or other food grade reagents with similar redox potential, may be useful processing methods to lower or eliminate IgE binding to food allergens.


Assuntos
Alérgenos/imunologia , Anacardium/imunologia , Temperatura Alta , Imunoglobulina E/metabolismo , Sulfitos/farmacologia , Albuminas 2S de Plantas/química , Albuminas 2S de Plantas/imunologia , Adolescente , Adulto , Alérgenos/química , Alérgenos/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Antígenos de Plantas/química , Antígenos de Plantas/efeitos dos fármacos , Antígenos de Plantas/imunologia , Criança , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina G/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Estrutura Molecular , Nozes/imunologia , Proteínas de Plantas/química , Proteínas de Plantas/efeitos dos fármacos , Proteínas de Plantas/imunologia , Coelhos
16.
Int J Environ Health Res ; 24(6): 515-27, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24382092

RESUMO

This study aims to investigate the effects of O3 in protein content and immunoglobulin E (IgE)-binding profiles of Acer negundo, Platanus x acerifolia and Quercus robur pollen. Pollen was exposed to O3 in an environmental chamber, at half, equal and four times the limit value for the human health protection in Europe. Pollen total soluble protein was determined with Coomassie Protein Assay Reagent, and the antigenic and allergenic properties were investigated by SDS-PAGE and immunological techniques using patients' sera. O3 exposure affected total soluble protein content and some protein species within the SDS-PAGE protein profiles. Most of the sera revealed increased IgE reactivity to proteins of A. negundo and Q. robur pollen exposed to the pollutant compared with the non-exposed one, while the opposite was observed in P. x acerifolia pollen. So, the modifications seem to be species dependent, but do not necessarily imply that increase allergenicity would occur in atopic individuals.


Assuntos
Acer , Alérgenos/efeitos dos fármacos , Imunoglobulina E/imunologia , Ozônio/farmacologia , Pólen/efeitos dos fármacos , Quercus , Traqueófitas , Poluentes Atmosféricos/farmacologia , Alérgenos/imunologia , Oxidantes/farmacologia , Pólen/imunologia
17.
Vet Immunol Immunopathol ; 153(3-4): 227-39, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23561552

RESUMO

Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in the Netherlands, by sequence homology searches on the C. obsoletus specific RNA database, with previously described allergens from C. nubeculosus and C. sonorensis. BLAST searches with these described allergens resulted in similarity hits with 7 genes coding for C. obsoletus allergens. These allergens were expressed as hexahistidine tagged recombinant proteins in E. coli. Allergens were termed Cul o 1-Cul o 7. A maltase (Cul o 1) plus Cul s 1 (maltase of C. sonorensis) were additionally expressed in insect cells using the baculovirus expression system to compare homologous allergens from different species produced with different expression systems in diagnostic in vitro and in vivo tests. We demonstrate that IBH affected horses in the Netherlands show higher IgE levels to Cul o 1 than to Cul s 1, as determined by an IgE ELISA. Furthermore, we show that Cul o 1 produced in E. coli is at least as suitable for in vitro diagnosis of IBH affected horses as Cul o 1 produced in the baculovirus/insect cell expression system. The resulting proteins were evaluated for their ability to discriminate IBH affected and healthy horses by ELISA and intradermal testing. The frequency of positive test results by ELISA within IBH affected horses ranged from 38% to 67% for the different allergens. When results of IgE-binding to Cul o 1-Cul o 7 were combined the test had a sensitivity of 92% and specificity of 85%. The capability of the allergens to induce Type I hypersensitivity reaction in IBH affected horses was demonstrated by an intradermal test. The results show that E. coli expressed recombinant allergens from C. obsoletus are valuable tools to determine the allergen specific sensitisation profile (component resolved diagnosis) in horses with IBH in countries were C. obsoletus is the most abundant species and may facilitate in the development of future immunotherapy.


Assuntos
Alérgenos/genética , Ceratopogonidae/imunologia , Doenças dos Cavalos/diagnóstico , Hipersensibilidade/veterinária , Mordeduras e Picadas de Insetos/veterinária , Alérgenos/efeitos dos fármacos , Animais , Baculoviridae/genética , Clonagem Molecular , Escherichia coli/genética , Cavalos , Hipersensibilidade/diagnóstico , Imunoglobulina E/sangue , Mordeduras e Picadas de Insetos/diagnóstico , Mordeduras e Picadas de Insetos/imunologia , Proteínas Recombinantes
18.
Braz. j. med. biol. res ; 45(11): 1002-1010, Nov. 2012. ilus
Artigo em Inglês | LILACS | ID: lil-650578

RESUMO

Ricinus communis L. is of great economic importance due to the oil extracted from its seeds. Castor oil has been used for pharmaceutical and industrial applications, as a lubricant or coating agent, as a component of plastic products, as a fungicide or in the synthesis of biodiesel fuels. After oil extraction, a castor cake with a large amount of protein is obtained. However, this by-product cannot be used as animal feed due to the presence of toxic (ricin) and allergenic (2S albumin) proteins. Here, we propose two processes for detoxification and allergen inactivation of the castor cake. In addition, we establish a biological test to detect ricin and validate these detoxification processes. In this test, Vero cells were treated with ricin, and cell death was assessed by cell counting and measurement of lactate dehydrogenase activity. The limit of detection of the Vero cell assay was 10 ng/mL using a concentration of 1.6 x 10(5) cells/well. Solid-state fermentation (SSF) and treatment with calcium compounds were used as cake detoxification processes. For SSF, Aspergillus niger was grown using a castor cake as a substrate, and this cake was analyzed after 24, 48, 72, and 96 h of SSF. Ricin was eliminated after 24 h of SSF treatment. The cake was treated with 4 or 8% Ca(OH)2 or CaO, and both the toxicity and the allergenic properties were entirely abolished. A by-product free of toxicity and allergens was obtained.


Assuntos
Animais , Alérgenos/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Compostos de Cálcio/farmacologia , Ricinus communis/efeitos dos fármacos , Inativação Metabólica , Alérgenos/toxicidade , Aspergillus niger/efeitos dos fármacos , Chlorocebus aethiops , Ricinus communis/toxicidade , Morte Celular/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Ativação Enzimática , Fermentação , L-Lactato Desidrogenase/metabolismo , Mastócitos/efeitos dos fármacos , Ricina/isolamento & purificação , Ricina/toxicidade , Fatores de Tempo , Testes de Toxicidade , /isolamento & purificação , /toxicidade , Células Vero
19.
J Occup Environ Hyg ; 9(11): 663-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23016564

RESUMO

The occurrence and distribution of mold on household surfaces and the efficacy of bleach-based (sodium hypochlorite, NaOCl) disinfectants on mold viability and allergenicity was documented. Household microenvironments prone to increased moisture were specifically targeted. Using the sticky tape method, 1330 samples were collected from non-porous indoor surfaces of 160 homes across the United States, and analyzed for mold. Homes were randomly selected and recruited via phone interviews. Culture and immunoassays were used to measure the viability and reduction of allergenic properties of Aspergillus fumigatus following 2.4% NaOCl treatment. All homes and 72.9% of surfaces tested positive for mold. Windowsills were the most frequently contaminated site (87.5%) and Cladosporium the most commonly identified mold (31.0%). Five-minute exposures to 2.4% NaOCl resulted in a >3 to >6-log10 reduction of culturable mold counts in controlled laboratory studies. Organisms were nonculturable after 5- and 10-min contact times on non-porous and porous ceramic carriers, respectively, and A. fumigatus spore-eluted allergen levels were reduced by an average 95.8% in 30 sec, as indicated by immunoassay. All homes are contaminated with some level of mold, and regrowth is likely in moisture-prone microenvironments. The use of low concentrations (2.4%) of NaOCl for the reduction of culturable indoor mold and related allergens is effective and recommended.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Alérgenos/efeitos dos fármacos , Desinfetantes/farmacologia , Fungos/efeitos dos fármacos , Características de Residência , Hipoclorito de Sódio/farmacologia , Antígenos de Fungos/efeitos dos fármacos , Antígenos de Fungos/imunologia , Fungos/imunologia , Fungos/isolamento & purificação , Humanos , Distribuição Aleatória , Esporos Fúngicos/imunologia , Fatores de Tempo , Estados Unidos
20.
Braz J Med Biol Res ; 45(11): 1002-10, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22911344

RESUMO

Ricinus communis L. is of great economic importance due to the oil extracted from its seeds. Castor oil has been used for pharmaceutical and industrial applications, as a lubricant or coating agent, as a component of plastic products, as a fungicide or in the synthesis of biodiesel fuels. After oil extraction, a castor cake with a large amount of protein is obtained. However, this by-product cannot be used as animal feed due to the presence of toxic (ricin) and allergenic (2S albumin) proteins. Here, we propose two processes for detoxification and allergen inactivation of the castor cake. In addition, we establish a biological test to detect ricin and validate these detoxification processes. In this test, Vero cells were treated with ricin, and cell death was assessed by cell counting and measurement of lactate dehydrogenase activity. The limit of detection of the Vero cell assay was 10 ng/mL using a concentration of 1.6 x 10(5) cells/well. Solid-state fermentation (SSF) and treatment with calcium compounds were used as cake detoxification processes. For SSF, Aspergillus niger was grown using a castor cake as a substrate, and this cake was analyzed after 24, 48, 72, and 96 h of SSF. Ricin was eliminated after 24 h of SSF treatment. The cake was treated with 4 or 8% Ca(OH)2 or CaO, and both the toxicity and the allergenic properties were entirely abolished. A by-product free of toxicity and allergens was obtained.


Assuntos
Alérgenos/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Compostos de Cálcio/farmacologia , Inativação Metabólica , Ricinus communis/efeitos dos fármacos , Albuminas 2S de Plantas/isolamento & purificação , Albuminas 2S de Plantas/toxicidade , Alérgenos/toxicidade , Animais , Aspergillus niger/efeitos dos fármacos , Ricinus communis/toxicidade , Morte Celular/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Chlorocebus aethiops , Ativação Enzimática , Fermentação , L-Lactato Desidrogenase/metabolismo , Mastócitos/efeitos dos fármacos , Ricina/isolamento & purificação , Ricina/toxicidade , Fatores de Tempo , Testes de Toxicidade , Células Vero
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