RESUMO
BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.
Assuntos
Hipersensibilidade Alimentar , Prunus persica , Humanos , Prunus persica/efeitos adversos , Hipersensibilidade Alimentar/diagnóstico , Alérgenos , Antígenos de Plantas , Imunoglobulina E , Proteínas de PlantasRESUMO
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.
Assuntos
Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/normas , Hipersensibilidade Alimentar/prevenção & controle , Animais , Humanos , Imunoglobulina E/imunologiaRESUMO
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. METHODS: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. RESULTS: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. CONCLUSIONS: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.
Assuntos
Alérgenos/imunologia , Dessensibilização Imunológica , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/terapia , Alimentos/efeitos adversos , Imunoglobulina E/imunologia , Alérgenos/administração & dosagem , Animais , Dessensibilização Imunológica/métodos , Humanos , Razão de Chances , Qualidade de Vida , Imunoterapia Sublingual , Resultado do TratamentoRESUMO
A dose-response relationship between toothbrushing frequency and the incidence of dental caries has not been confirmed. Furthermore, no longitudinal study about this relationship has considered dental caries experience at baseline, which is an important factor influencing the frequency of future caries. OBJECTIVE: To elucidate the association between the incidence of dental caries and toothbrushing frequency after adjusting for dental caries experience at baseline in a Japanese population. BASIC RESEARCH DESIGN: The 92 recruits of the Japan Maritime Self-Defense Force in Kure, Japan, in 2011 were followed up for 3 years. They underwent oral examination at the annual checkups and answered questions about toothbrushing frequency. MAIN OUTCOME MEASURES: The multiple logistic regression analysis was used to analyze the incidence of dental caries and to identify independent effects of toothbrushing frequency and dental caries experience at baseline. Furthermore, the relative importance of the incidence of dental caries was investigated among other independent variables using the partial adjusted R² score. RESULTS: Logistic regression analysis showed that toothbrushing frequency alone did not influence the increment in decayed, missing, and filled teeth (DMFT). However, DMFT at baseline alone was associated with the increment in DMFT (crude odds ratio, OR, 1.20, 95% confidence interval, CI, 1.08,1.33). In the fully adjusted model, only DMFT at baseline was associated with the increment in DMFT (adjusted OR 1.23, 95%CI 1.09,1.38). CONCLUSION: After three years, the incidence of dental caries in young adult Japanese males was influenced by DMFT at baseline, rather than toothbrushing frequency.
Assuntos
Cárie Dentária/epidemiologia , Escovação Dentária/estatística & dados numéricos , Índice CPO , Humanos , Incidência , Japão/epidemiologia , Estudos Longitudinais , Masculino , Fumar/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. OBJECTIVE: The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. METHODS: Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). RESULTS: Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA /L) were 86.1% and 85.7%, respectively. CONCLUSION AND CLINICAL RELEVANCE: Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.
Assuntos
Albuminas 2S de Plantas/imunologia , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Sesamum/efeitos adversos , Alérgenos/administração & dosagem , Especificidade de Anticorpos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E/metabolismo , Biomarcadores/metabolismo , Humanos , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Hipersensibilidade Imediata/terapia , Testes Imunológicos/métodos , Medicina de Precisão/métodosAssuntos
Actinidia/imunologia , Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/diagnóstico , Imunoglobulina E/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Lactente , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available. OBJECTIVE: To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma. METHODS: The study was performed from March to August 2009. Patients in physicians' waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis. RESULTS: In this study, 1910 physicians enrolled 29,518 asthmatics; 15,051 (51.0%) questionnaires were administered by physician, and 26,680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician's diagnosis of rhinitis. Most patients with the physician's diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician's diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician's diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%). CONCLUSION: Rhinitis is common in asthma and impairs asthma control.
Assuntos
Asma/complicações , Rinite/complicações , Rinite/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto JovemAssuntos
Arachis/efeitos adversos , Dessensibilização Imunológica , Hipersensibilidade a Amendoim/prevenção & controle , Alérgenos/administração & dosagem , Alérgenos/imunologia , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Humanos , Lactente , Guias de Prática Clínica como Assunto , Fatores de TempoRESUMO
Food allergies have increased in recent years in Japan. Details of causative foods, places where anaphylaxis developed, and other allergic factors remain unknown, and we investigated them. A'questionnaire survey for the prevention of food allergies' was conducted using a nationwide group of patients with food allergies. A total of 1383 patients from 878 families (including 319 patients who experienced anaphylaxis) provided valid answers to the questionnaire. The average age of the first anaphylactic attack was 3.20 +/- 6.327 yr. The most common allergens causing anaphylaxis were in order milk, eggs, wheat, peanuts, and soybeans, followed by sesame and buckwheat. The most common place where anaphylaxis developed was the patient's own home, followed by fast food restaurants, places visited, restaurants, and schools. In patients' own homes, fast food restaurants (buffet), places visited and schools, the most common allergens were milk, eggs, and wheat. In restaurants and accommodation facilities, eggs were the most common allergen followed by milk. As possible food allergies can cause anaphylaxis, it is necessary to provide precise information for consumers regarding packaged and processed foods.
Assuntos
Alérgenos , Anafilaxia/epidemiologia , Hipersensibilidade Alimentar/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Coleta de Dados , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Inquéritos e QuestionáriosRESUMO
Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.
RESUMO
Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.
RESUMO
Cytomegalovirus-specific cytotoxic T-lymphocytes (CMV-CTL) are essential for the control of CMV reactivation. To monitor the quantity and function of CMV-CTL after hematopoietic stem cell transplantation (HSCT), two CMV epitopes that bind to HLA-A*0201 NLVPMVATV (A*02NLV) and HLA-A*2402 QYDPVAALF (A*24QYD) were evaluated for their immunological potential. Samples from patients with the HLA-A*02 or HLA-A*24 serotype were analyzed by tetramer, intracellular cytokine staining and enzyme-linked immunospot (ELISPOT) assay. There were significantly more A*02NLV-specific CMV-CTL than A*24QYD (23 x 10(6) vs 0.4 x 10(6)/l). The frequency of IFN-gamma-producing cells was also higher upon stimulation with A*02NLV than with A*24QYD (2.5 vs 0.1%/CD8). Furthermore, the magnitude of CMV-CTL expansion was two- to 50-fold when cells were cultured with A*02NLV, while only an insignificant increase was observed in culture with A*24QYD. Although the number of A*24QYD-specific CMV-CTL was very low in most of the HLA-A*24 patients, the incidence of CMV reactivation did not differ between those with HLA-A*02 and HLA-A*24 serotype alone. These results suggest that an epitope other than A*24QYD plays a major role in patients with HLA-A*24. Our study also showed that A*02NLV may be a useful epitope for monitoring CMV-CTL not only in patients with HLA-A*0201 but also in those with the A*0206 genotype.
Assuntos
Citomegalovirus/imunologia , Antígenos HLA-A/imunologia , Transplante de Células-Tronco Hematopoéticas , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Antígenos Virais/imunologia , Células Cultivadas , Epitopos de Linfócito T/imunologia , Feminino , Antígeno HLA-A2 , Antígeno HLA-A24 , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Neoplasias/virologia , Fenótipo , Transplante Homólogo , Ativação Viral/imunologiaRESUMO
Canine mammary tumours (CMTs) are the most common neoplasms affecting female dogs. There is an urgent need for molecular biomarkers that can detect early stages of the disease in order to improve accuracy of CMT diagnosis. The aim of this study was to examine whether caveolin-1 (Cav-1) and matrix metalloproteinase 14 (MMP14) are associated with CMT histological malignancy and invasion. Sixty-five benign and malignant CMT samples and six normal canine mammary glands were analysed using quantitative reverse transcription-polymerase chain reaction. Cav-1 and MMP14 genes were highly expressed in CMT tissues compared to normal tissues. Cav-1 especially was overexpressed in malignant and invasive CMT tissues. When a CMT cell line was cultured on fluorescent gelatin-coated coverslips, localisation of Cav-1 was observed at invadopodia-mediated degradation sites of the gelatin matrix. These findings suggest that Cav-1 may be involved in CMT invasion and that the markers may be useful for estimating CMT malignancy.
Assuntos
Caveolina 1/metabolismo , Doenças do Cão/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Mamárias Animais/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Animais , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Caveolina 1/genética , Linhagem Celular Tumoral , Cães , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Metaloproteinase 14 da Matriz/genéticaRESUMO
In human HL-60 promyelocytic leukemia cells, diazepinylbenzoic acid derivatives can exhibit either antagonistic or synergistic effects on the differentiation-inducing activities of natural or synthetic retinoids, the activity depending largely on the nature of the substituents on the diazepine ring. Thus, a benzolog of the retinoid antagonist LE135 (6), 4-(13H-10,11,12,13-tetrahydro-10, 10,13,13,15-pentamethyldinaphtho[2,3-b][1,2-e]diazepin-7-yl) benzoic acid (LE540, 17), exhibits a 1 order of magnitude higher antagonistic potential than the parental LE135 (6). In contrast, 4-[5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyldibenzo[b,e] [1,4]diazepin-11-yl]-benzoic acid (HX600, 7), a structural isomer of the antagonistic LE135 (6), enhanced HL-60 cell differentiation induced by RAR agonists, such as Am80 (2). This synergistic effect was further increased for a thiazepine, HX630 (29), and an azepine derivative, HX640 (30); both synergized with Am80 (2) more potently than HX600 (7). Notably, the negative and positive effects of the azepine derivatives on retinoidal actions can be related to their RAR-antagonistic and RXR-agonistic properties, respectively, in the context of the RAR-RXR heterodimer.
Assuntos
Azepinas/farmacologia , Receptores do Ácido Retinoico/metabolismo , Retinoides/farmacologia , Fatores de Transcrição/metabolismo , Azepinas/síntese química , Azepinas/química , Azepinas/metabolismo , Benzoatos/farmacologia , Ligação Competitiva , Diferenciação Celular/efeitos dos fármacos , Dibenzazepinas/farmacologia , Dimerização , Sinergismo Farmacológico , Células HL-60 , Humanos , Estrutura Molecular , Ligação Proteica , Receptores X de Retinoides , Retinoides/agonistas , Retinoides/antagonistas & inibidores , Retinoides/metabolismo , Tetra-Hidronaftalenos/farmacologiaRESUMO
Extracellular ATP stimulated histamine release and generation of leukotrience C4 (LTC4) accompanied with the formation of inositol phosphates and a rapid increase in intracellular Ca2+ ([Ca2+]i) in mouse bone marrow-derived cultured mast cells (BMMC). The rank order of histamine-releasing potency of ATP and its metabolites is ATP greater than ADP greater than AMP greater than adenosine. Nonhydrolyzable ATP analog, adenosine-5'-O-[2-thiotriphosphate] (ATP-S) released more histamine from the cells than ATP. On the other hand, simultaneous addition of adenosine analogues at micromolar concentrations potentiated histamine release from the cells induced by ATP (50 microM) or DNP-HSA antigen (0.1 ng/ml) in the following rank order: adenosine greater than AMP much greater than ADP = ATP. Histamine release potentiated by adenosine was blocked by the treatment with pertussis toxin, whereas histamine release induced by ATP was not affected by the toxin, suggesting that extracellular ATP stimulate histamine release from BMMC probably via mechanisms independent of the potentiation of histamine release induced by adenosine.
Assuntos
Trifosfato de Adenosina/imunologia , Liberação de Histamina , Mastócitos/metabolismo , Adenosina/imunologia , Difosfato de Adenosina/imunologia , Monofosfato de Adenosina/imunologia , Animais , Células da Medula Óssea , Células Cultivadas , Mastócitos/imunologia , CamundongosRESUMO
The adrenal function of children with near fatal asthma was evaluated by a modified rapid ACTH test. The rapid ACTH tests, which were performed within six months of each life-threatening asthmatic episode, showed extremely low responsiveness. The response in the subjects was significantly lower than that of patients who had received high dose of corticosteroid therapy. It was suggested that the adrenocortical function of children with near fatal asthma had been already suppressed and that adrenal suppression could easily occur in such patients. We advocate the following measures: (1) environmental control, education of patients and their families, physical training accurate medication should be supplied to reduce the use of corticosteroids, (2) sufficient doses of corticosteroids should, however be given to patients with acute exacerbation, (3) not only lung function tests or allergic examinations, but also adrenocortical function tests should be performed on severe asthmatic patients.
Assuntos
Córtex Suprarrenal/fisiopatologia , Asma/fisiopatologia , Adolescente , Testes de Função do Córtex Suprarrenal , Hormônio Adrenocorticotrópico , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
We studied the protective effect of sustained-release theophylline granules on early or late response in exercise-induced asthma (EIA) in 16 patients ranging in age from 7 to 18 years. A standardized exercise test was examined 2 hours after administration of theophylline granules on one day and after no medication on another day. On both days, the lung functions and the serum theophylline and cortisol concentrations of the patients were examined before exercise and over a period of 8 hours after exercise. On days without medication, early response was seen in 16 patients and late response in 6. On days with medication, the theophylline granules inhibited early response in 13 of the 16 patients and late response in 5 of the 6 patients. This suggests that theophylline preparation is a useful drug for inhibiting the dual responses of EIA.
Assuntos
Asma Induzida por Exercício/tratamento farmacológico , Teofilina/administração & dosagem , Adolescente , Asma Induzida por Exercício/prevenção & controle , Criança , Preparações de Ação Retardada , Avaliação de Medicamentos , Teste de Esforço , Feminino , Humanos , Masculino , Teofilina/uso terapêuticoRESUMO
When mononuclear cells from umbilical-cord blood were cultured for 3 weeks, low concentrations of interleukin 3 supported the preferential growth of basophils, with eosinophils comprising a smaller proportion. These basophils contained 0.15-0.3 microgram histamine per 10(6) cells, and released histamine by the IgE-dependent and -independent stimuli. Interleukin 5 increased the number and proportion of eosinophils in a dose-dependent manner without affecting the proliferation of other cell types in the interleukin 3-supplemented cultures. These cultured eosinophils could be activated by platelet-activating factor.
Assuntos
Basófilos/citologia , Diferenciação Celular/efeitos dos fármacos , Eosinófilos/citologia , Sangue Fetal/citologia , Interleucina-3/farmacologia , Interleucina-5/farmacologia , Células Cultivadas , Humanos , Proteínas Recombinantes/farmacologiaRESUMO
The measurement of allergen-specific IgE antibodies and total IgE was performed with LUMIWARD immunoassay system (chemiluminescent enzyme immunoassay) using 406 serum samples obtained from patients with various allergic diseases and 81 serum samples from normal donors. These were collected by departments of internal medicine, pediatrics, dermatology and otorynolaryngology at eleven institutes in Japan. In addition to a comparative study with CAP RAST, skin tests were also performed to establish a clinical diagnosis. Simultaneous measurements were performed and an excellent correlation with CAP RAST was observed with a concordance rate of 92.6% and correlation coefficient of 0.922. The specificity determined by the normal serum samples was 96.4% for CAP RAST and 96.2% for LUMIWARD. The sensitivity determined by the samples, of which etiological allergens were identified clinically, was 84.8% for CAP RAST and 85.5% for LUMIWARD. Among them, the sensitivity of skin test was 91.8%. The concordance rate with clinical diagnosis was as high as 90.6% and 90.8% for CAP RAST and LUMIWARD. The normal upper limit of total IgE by cumulative 95% value was calculated to be 170 IU/ml for adult subjects. These results indicate the clinical usefulness of the LUMIWARD immunoassay system in evaluating IgE antibodies and total IgE.