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1.
Medicine (Baltimore) ; 100(39): e27314, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596130

RESUMO

ABSTRACT: This study aimed to evaluate the correlation between fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in allergic rhinitis (AR) and patients with or without bronchial asthma (BA).A total of 90 patients who were diagnosed with persistent AR (AR group, n = 30), BA (BA group, n = 30), or allergic rhinitis with bronchial asthma (AR-BA) (AR-BA group, n = 30), were enrolled in this study, along with 30 healthy adult volunteers (control group, n = 30). The participants were further divided into 2 groups based on the results of a skin-prick test (SPT): a highly atopic group (SPT = 3+ and above) and a moderately atopic group (SPT = 2+ and below). All participants underwent FeNO and nNO measurement, an absolute blood eosinophil count, total serum immunoglobulin measurement, and horizontal baseline lung capacity determination.The results showed that the FeNO levels in the 3 observation groups were significantly higher than those in the control group (P < .01), and in the BA group they were significantly higher than in the AR-BA group (P < .01). The levels of nNO in both the AR group and the AR-BA group were higher than those in the control group and the BA group (P < .01), but there was no significant difference between the AR group and the AR-BA group (P > .05). The levels of nNO in the BA group were also significantly different from those in the control group (P < .01).FeNO and nNO are positively correlated with the degree of AR in patients with BA; therefore, nNO levels can be used as an inflammatory marker of AR in patients with BA. FeNO can also be used as an inflammatory marker of AR in patients complicated with BA as a warning indicator of asthma.


Assuntos
Asma/epidemiologia , Asma/patologia , Óxido Nítrico/análise , Nariz/patologia , Rinite Alérgica/epidemiologia , Rinite Alérgica/patologia , Adolescente , Adulto , Idoso , Eosinófilos/metabolismo , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Adulto Jovem
2.
Ann Allergy Asthma Immunol ; 127(5): 530-535, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34688426

RESUMO

OBJECTIVE: To identify treatment approaches that can be used in the management of patients with asthma who lack significant type 2 inflammation, also called T2 low asthma. DATA SOURCES: Recent expert guideline updates on the management of asthma, recent journal articles and review articles, and foundational journal articles are referenced. STUDY SELECTIONS: This review cites clinical cohort studies of highly characterized patients with asthma, clinical interventional trials of high impact, mechanistic studies relevant to T2 low asthma, and emerging work in this area. RESULTS: T2 low asthma accounts for approximately one-third to one-half of individuals with asthma. Characteristics of participants with T2 low asthma include higher body mass index, cigarette smoking/smoke exposure, relative lack of responsiveness to steroids, less bronchodilator reversibility, and often the presence of neutrophilic inflammation. Multiple available interventions target these characteristics, including standard inhalers, azithromycin, and lifestyle interventions of weight loss and smoking cessation. CONCLUSION: Treatment of T2 low asthma should involve currently available approaches and will benefit from improved definition and understanding of disease pathobiology.


Assuntos
Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Broncodilatadores/uso terapêutico , Adolescente , Adulto , Antiasmáticos/uso terapêutico , Índice de Massa Corporal , Criança , Pré-Escolar , Humanos , Imunoglobulina E/sangue , Inflamação/patologia , Agonistas Muscarínicos/uso terapêutico , Neutrófilos/imunologia , Índice de Gravidade de Doença , Abandono do Hábito de Fumar
3.
Nutrients ; 13(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34684380

RESUMO

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.


Assuntos
Asma/terapia , Alimentos e Bebidas Fermentados , Inflamação/patologia , Pulmão/patologia , Soja/química , Animais , Peso Corporal , Líquido da Lavagem Broncoalveolar , Contagem de Células , Citocinas/metabolismo , Dieta , Modelos Animais de Doenças , Eosinófilos/metabolismo , Comportamento Alimentar , Feminino , Imunoglobulina E/sangue , Inflamação/sangue , Camundongos Endogâmicos BALB C , Ovalbumina
4.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576095

RESUMO

Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity.


Assuntos
Asma/patologia , Proteínas de Transporte/genética , Hipersensibilidade/patologia , Inflamação/patologia , Pulmão/patologia , Nanopartículas/toxicidade , Tiorredoxinas/genética , Titânio/toxicidade , Regulação para Cima/genética , Animais , Apoptose , Asma/sangue , Asma/complicações , Asma/genética , Líquido da Lavagem Broncoalveolar , Proteínas de Transporte/metabolismo , Caspase 3/metabolismo , Contagem de Células , Linhagem Celular , Fenômenos Químicos , Citocinas/biossíntese , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/complicações , Hipersensibilidade/genética , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/genética , Mediadores da Inflamação/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , Muco/metabolismo , Nanopartículas/ultraestrutura , Ovalbumina , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Hipersensibilidade Respiratória/complicações , Tiorredoxinas/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
5.
Front Immunol ; 12: 681714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539625

RESUMO

Background: Chronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU. Patients and Methods: Genome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases. Results: A total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δß| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δß| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively. Conclusion: This study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU.


Assuntos
Urticária Crônica/etiologia , Metilação de DNA , Epigênese Genética , Transcriptoma , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoimunidade , Estudos de Casos e Controles , Urticária Crônica/diagnóstico , Biologia Computacional/métodos , Ilhas de CpG , Suscetibilidade a Doenças/imunologia , Perfilação da Expressão Gênica , Ontologia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia
6.
Front Immunol ; 12: 723585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489974

RESUMO

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Citocinas/sangue , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , COVID-19/classificação , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
7.
Pak J Biol Sci ; 24(9): 920-927, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34585544

RESUMO

<b>Background and Objective:</b> COVID-19 is a fast-spreading worldwide pandemic caused by SARS-CoV-2. The World Health Organization recommended wearing face masks. Masks have become an urgent necessity throughout the pandemic, the study's goal was to track the impact of wearing masks on immunological responses. <b>Materials and Methods:</b> This study was conducted on 40 healthy people who were working in health care at Nineveh Governorate Hospitals from September-December, 2020. They wore face masks at work for more than 8 months for an average of 6 hrs a day. The control sample included 40 healthy individuals, who wore masks for very short periods. All samples underwent immunological and physiological tests to research the effects of wearing masks for extended periods within these parameters. <b>Results:</b> The results showed a significant decrease in total White Blood Count and the absolute number of neutrophils, lymphocytes, monocytes and phagocytic activity. However, there was a significant increase in the absolute number of eosinophils in participants compared with the control. The results also suggested there were no significant differences in IgE, haemoglobin concentration and blood O<sub>2 </sub>saturation in participants who wore masks for more than 6 hrs compared to the control group. The results showed a significant increase in pulse rate in participants who wore masks for more than 6 hrs compared to the control group. The results also showed a strong correlation coefficient between the time of wearing masks and some immunological, haematological parameters. <b>Conclusion:</b> Wearing masks for long periods alters immunological parameters that initiate the immune response, making the body weaker in its resistance to infectious agents.


Assuntos
COVID-19/prevenção & controle , Exposição por Inalação/prevenção & controle , Leucócitos/imunologia , Máscaras , Exposição Ocupacional/prevenção & controle , Fagócitos/imunologia , SARS-CoV-2/patogenicidade , Adulto , Biomarcadores/sangue , COVID-19/transmissão , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Hemoglobinas/metabolismo , Humanos , Imunoglobulina E/sangue , Exposição por Inalação/efeitos adversos , Contagem de Leucócitos , Masculino , Máscaras/efeitos adversos , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Oxigênio/sangue , Recursos Humanos em Hospital , Fagocitose , Fatores de Tempo
8.
J Environ Pathol Toxicol Oncol ; 40(3): 63-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587405

RESUMO

Allergic rhinitis (AR) is a common type of inflammatory disease with symptoms including rhinorrhea, fatigue, sneezing, and disturbed sleep. AR affects nearly 40% of peoples worldwide with the increased numbers of new cases. In this work, the study was conducted to disclose the anti-inflammatory and antiallergic properties of cirsilineol against the ovalbumin (OVA)-sensitized AR in mice. AR was provoked in BALB/c mice through the OVA challenge 30 days along with 10 and 20 mg/kg of cirsilineol treatment. The nasal symptoms, i.e., rubbing and sneezing was monitored after the final OVA challenge. The status of OVA-specific IgE, PGD2, and LTC4 was investigated using assay kits. The status of pro-inflammatory markers also examined using assay kits. The levels of oxidative markers, SOD activity, and pro-inflammatory markers in the spleen mononuclear cells (SMEs) were studied by using respective assay kits. The mRNA expression of TXNIP was assessed using RT-PCR study. The 10 and 20 mg/kg of cirsilineol treatment effectively decreased the sneezing and nasal rubbings in OVA-provoked mice. Cirsilineol also decreased the IgE, PGD2, and LTC4 status in the AR animals. The status of pro-inflammatory markers, i.e., IL-4, IL-5, IL-6, IL-33 and TNF-α was found to be decreased in the cirsilineol administered AR mice. Cirsilineol effectively reduced the ROS and MDA and improved SOD in the OVA-challenged SMCs. The mRNA expression of TXNIP was appreciably suppressed by the cirsilineol treatment. Altogether, these findings proved the beneficial actions of cirsilineol against the OVA-triggered AR in mice. The additional studies on the cirsilineol could lead to the development of new drug for AR management.


Assuntos
Antialérgicos/farmacologia , Flavonas/farmacologia , Rinite Alérgica/prevenção & controle , Animais , Biomarcadores/metabolismo , Proteínas de Transporte/genética , Células Cultivadas , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Histamina/sangue , Imunoglobulina E/sangue , Imunoglobulina E/metabolismo , Leucotrieno C4/metabolismo , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal , Ovalbumina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Prostaglandina D2/metabolismo , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/imunologia , Baço/citologia , Tiorredoxinas/genética
9.
Cells ; 10(7)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34360010

RESUMO

BACKGROUND: Until now, the cost of allergy treatment in the insured public health care system and the non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. OBJECTIVE: To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in a non-insured self-financing private health care system. METHODS: A retrospective cohort study conducted from 2015 until 2020 that compared the clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1098 subjects. RESULTS: A decrease in sp-HDM-IgE level (kU/mL) from 20.5 + 8.75 kU/mL to 12.1 + 3.07 kU/mL was observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT, it costs IDR 21,753,062.7 per child, and for non-SCIT, it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT, it costs IDR 17,024,138.8, while with non-SCIT, it costs IDR 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT, it costs IDR 9,550,126.6, while with non-SCIT, it costs IDR 52,073,938.9. CONCLUSIONS: In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.


Assuntos
Análise Custo-Benefício , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica/economia , Rinite Alérgica/economia , Rinite Alérgica/terapia , Adolescente , Alérgenos/administração & dosagem , Alérgenos/química , Alérgenos/imunologia , Animais , Criança , Pré-Escolar , Misturas Complexas/administração & dosagem , Misturas Complexas/isolamento & purificação , Dermatophagoides pteronyssinus/química , Dessensibilização Imunológica/métodos , Feminino , Humanos , Imunoglobulina E/sangue , Indonésia , Lactente , Recém-Nascido , Injeções Subcutâneas , Masculino , Prática Privada/economia , Estudos Retrospectivos , Rinite Alérgica/imunologia , Rinite Alérgica/patologia
10.
Nutrients ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34444651

RESUMO

Cow's milk allergy is a common food allergy in infants, and is associated with an increased risk of developing other allergic diseases. Dietary selenium (Se), one of the essential micronutrients for humans and animals, is an important bioelement which can influence both innate and adaptive immune responses. However, the effects of Se on food allergy are still largely unknown. In the current study it was investigated whether dietary Se supplementation can inhibit whey-induced food allergy in an animal research model. Three-week-old female C3H/HeOuJ mice were intragastrically sensitized with whey protein and cholera toxin and randomly assigned to receive a control, low, medium or high Se diet. Acute allergic symptoms, allergen specific immunoglobulin (Ig) E levels and mast cell degranulation were determined upon whey challenge. Body temperature was significantly higher in mice that received the medium Se diet 60 min after the oral challenge with whey compared to the positive control group, which is indicative of impaired anaphylaxis. This was accompanied by reductions in antigen-specific immunoglobulins and reduced levels of mouse mast cell protease-1 (mMCP-1). This study demonstrates that oral Se supplementation may modulate allergic responses to whey by decreasing specific antibody responses and mMCP-1 release.


Assuntos
Dieta , Hipersensibilidade a Leite/dietoterapia , Selenometionina/administração & dosagem , Proteínas do Soro do Leite/imunologia , Anafilaxia/dietoterapia , Anafilaxia/imunologia , Ração Animal , Animais , Biomarcadores/sangue , Degranulação Celular , Células Cultivadas , Quimases/sangue , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Dermatite Alérgica de Contato/dietoterapia , Dermatite Alérgica de Contato/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos C3H , Hipersensibilidade a Leite/sangue , Hipersensibilidade a Leite/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
11.
BMC Pulm Med ; 21(1): 268, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404358

RESUMO

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Assuntos
Asma , COVID-19 , Curcumina , Eosinófilos , Imunoglobulina E/sangue , Administração Oral , Adulto , Assistência Ambulatorial/métodos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Asma/sangue , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/fisiopatologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Curcumina/administração & dosagem , Curcumina/efeitos adversos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
12.
J Immunol Methods ; 497: 113110, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34332973

RESUMO

The detection of allergen-specific IgE is of value for the diagnosis of children''s milk allergy. However, its accuracy will interfere with the presence of high levels of specific IgG in the serum of children with milk allergy. To solve this problem, we established a light-initiated chemiluminescent assay (LICA) based on nanomicrospheres, which neutralized the interference of specific IgG by increasing the amount of antigen coated on the microspheres. The ability of this method to resist IgG interference was confirmed by adding extra specific IgG to the serum of allergic patients. Finally, the positive rate of allergen-specific IgE was increased to 85%, which was better than the indirect ELISA (70%), indicating that this method has certain advantages for the detection of specific IgE in children with milk allergy.


Assuntos
Caseínas/imunologia , Ensaio de Imunoadsorção Enzimática , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Hipersensibilidade a Leite/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Luz , Medições Luminescentes , Hipersensibilidade a Leite/sangue , Hipersensibilidade a Leite/imunologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
13.
Int Arch Allergy Immunol ; 182(11): 1072-1076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34419947

RESUMO

BACKGROUND: Predicting food allergy resolution is essential to minimize the number of restricted foods in children. However, there have been no studies on the natural history of peanut allergy (PA) in Korea. OBJECTIVE: This study aimed to evaluate the natural course and prognostic factors of immediate-type PA in children till the age of 10 years. METHODS: We retrospectively collected data of 122 children who developed PA before 60 months of age from 3 tertiary hospitals in Korea. Diagnosis and resolution of PA was defined as an oral food challenge test or a convincing history of symptoms within 2 h after peanut ingestion. The prognostic factors for resolution of PA were identified using the Cox proportional hazard model. RESULTS: The median (interquartile range) age at diagnosis was 2.0 (1.3-3.0) years. Among the 122 children, PA resolved in 18 (14.8%) children. The level of peanut-specific IgE (sIgE) at diagnosis in the persistence group was significantly higher than that in the resolution group (p = 0.026). The probabilities of resolution of PA were 10.3% and 32.8% at the ages of 6 and 10 years, respectively. A peanut-sIgE level ≥1 kU/L at diagnosis was significantly associated with persistent PA (hazard ratio, 5.99; 95% confidence interval, 1.89-18.87). CONCLUSIONS: Only 10.3% of our patients had a probability of developing spontaneous resolution of PA by 6 years of age. Peanut-sIgE levels ≥1 kU/L at diagnosis were associated with the persistence of PA.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Arachis/imunologia , Imunoglobulina E/sangue , Hipersensibilidade a Amendoim/sangue , Criança , Pré-Escolar , Feminino , Humanos , Tolerância Imunológica , Imunoglobulina E/imunologia , Lactente , Masculino , Hipersensibilidade a Amendoim/imunologia , Prognóstico , República da Coreia , Estudos Retrospectivos
15.
Cells ; 10(8)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440807

RESUMO

Allergic asthma is a chronic and heterogeneous pulmonary disease in which platelets can be activated in an IgE-mediated pathway and migrate to the airways via CCR3-dependent mechanism. Activated platelets secrete IL-33, Dkk-1, and 5-HT or overexpress CD40L on the cell surfaces to induce Type 2 immune response or interact with TSLP-stimulated myeloid DCs through the RANK-RANKL-dependent manner to tune the sensitization stage of allergic asthma. Additionally, platelets can mediate leukocyte infiltration into the lungs through P-selectin-mediated interaction with PSGL-1 and upregulate integrin expression in activated leukocytes. Platelets release myl9/12 protein to recruit CD4+CD69+ T cells to the inflammatory sites. Bronchoactive mediators, enzymes, and ROS released by platelets also contribute to the pathogenesis of allergic asthma. GM-CSF from platelets inhibits the eosinophil apoptosis, thus enhancing the chronic inflammatory response and tissue damage. Functional alterations in the mitochondria of platelets in allergic asthmatic lungs further confirm the role of platelets in the inflammation response. Given the extensive roles of platelets in allergic asthma, antiplatelet drugs have been tested in some allergic asthma patients. Therefore, elucidating the role of platelets in the pathogenesis of allergic asthma will provide us with new insights and lead to novel approaches in the treatment of this disease.


Assuntos
Asma/patologia , Plaquetas/metabolismo , Imunidade Adaptativa , Asma/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/metabolismo , Integrinas/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Selectina-P/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Front Immunol ; 12: 664668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220812

RESUMO

Background: Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children. Objective: The present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma. Methods: Using a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1ß, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout. Results: The frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (P<0.01). RV1B-induced IL-1ß response and HDM-stimulated IL-5 production was higher in asthmatics than controls (P<0.05). In contrast, IL-1ß and IL-6 were significantly reduced in response to HDM and LPS in asthmatics compared to controls (P<0.05). Children with asthma also had reduced pulmonary function, indicated by lower respiratory reactance as well as higher area of-reactance and lung clearance index values compared with controls (P<0.05). Conclusion: Our study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.


Assuntos
Asma/imunologia , Imunidade Inata , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Fatores Etários , Asma/diagnóstico , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/biossíntese , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Testes de Função Respiratória
17.
Front Immunol ; 12: 687294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220841

RESUMO

Background: Several studies indicate that Der p 7 is an important and clinically relevant allergen of Dermatophagoides pteronyssinus which should be included in vaccines for treatment of house dust mite (HDM) allergy. Aim of this study was to characterize the IgE epitopes of Der p 7. Methods: Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1-P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes. Results: rDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7. Conclusion and Clinical Relevance: IgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Epitopos Imunodominantes , Imunoglobulina E/sangue , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Alérgenos/química , Alérgenos/genética , Animais , Antígenos de Dermatophagoides/química , Antígenos de Dermatophagoides/genética , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Mapeamento de Epitopos , Humanos , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Pyroglyphidae/genética , Coelhos , Ratos , Hipersensibilidade Respiratória/sangue
18.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34240224

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits antimalarial effects. The aim of the present study was to examine the therapeutic effects of quinine in AD­like mice. AD was induced with 2,4­dinitrochlorobenzene, and the mice were treated with 10 mg/kg quinine for 1, 4 and 7 days. A total of 60 BALB/c mice were divided into the following groups: Healthy, AD­like, AD­like + quinine and healthy + quinine, with 1, 4 and 7 days groups for each treatment. Blood was extracted from all mice and ELISA was performed to detect immunoglobulin E (IgE) levels. H&E­stained tissue sections were prepared from skin lesions on the backs of the mice and pathological changes were observed. Cytokines were detected via ELISA, and the filaggrin (FLG) and kallikrein­7 (KLK7) proteins were detected via western blotting and immunohistochemistry. IKKα and NF­κB mRNA were analyzed via reverse transcription­quantitative PCR. Quinine ameliorated skin damage in the AD­like mice, reduced IgE expression in the blood, inhibited expression of IKKα and NF­κB, reduced cytokine secretion, reduced KLK7 expression, reduced scratching frequency, increased FLG expression and repaired the skin barrier. These results suggested that quinine exhibited therapeutic effects in AD­like mice.


Assuntos
Dermatite Atópica/tratamento farmacológico , Quinina/farmacologia , Quinina/uso terapêutico , Animais , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Modelos Animais de Doenças , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Imunoglobulina E/sangue , Calicreínas/genética , Calicreínas/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia
19.
Environ Health ; 20(1): 81, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256787

RESUMO

BACKGROUND: Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. METHODS: Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. RESULTS: Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. CONCLUSIONS: Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.


Assuntos
Asma/urina , Índice de Massa Corporal , Carbanilidas/urina , Eczema/urina , Poluentes Ambientais/urina , Parabenos/análise , Fenóis/urina , Rinite/urina , Adolescente , Adulto , Asma/epidemiologia , Monitoramento Biológico , Criança , Cosméticos , Eczema/epidemiologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Rinite/epidemiologia , Adulto Jovem
20.
J Immunol Methods ; 496: 113101, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34273396

RESUMO

The diagnosis of a drug hypersensitivity reaction (DHR) is complex. The first step after taking the clinical history is to look for a sensitization to confirm or exclude the diagnosis and to identify the culprit drug. Skin tests are the primary means of detecting sensitization in DHR, but are associated with a risk for a severe reaction and may be contraindicated. In vitro tests offer the potential to support or confirm a diagnosis of DHR and influence medical decision making. For immediate-type DHR, a few validated assays for measurement of specific IgE (sIgE) are commercially available to a limited number of drugs. In addition, several home-made sIgE radioimmunoassays have been used in other studies. The sensitivity of the sIgE assay is drug-dependant and generally low (0-85%) for betalactams and reported heterogeneous for other drugs ranging from 26% for chlorhexidine and 44% for suxamethonium to 92% for chlorhexidine. However, as all these studies included patients, in whom DHR was confirmed only by skin tests and not by provocation, the results have to be interpreted carefully and may be unreliable. Determination of mediators during an acute phase of a reaction may indirectly support the diagnosis of a DHR by demonstrating mast cell and basophil mediator release. Negative in vitro tests do not exclude a DHR or imputability of a drug, but a positive result may support causality and eliminate the necessity for a drug provocation test. Unfortunately, evidence is limited with a lack of well-controlled studies in larger numbers of well-phenotyped patients, which results in susceptibility for bias and a need for future multicenter studies.


Assuntos
Basófilos/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Hipersensibilidade a Drogas/diagnóstico , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E/sangue , Testes Imunológicos , Mastócitos/efeitos dos fármacos , Animais , Especificidade de Anticorpos , Basófilos/imunologia , Basófilos/metabolismo , Biomarcadores/sangue , Hipersensibilidade a Drogas/sangue , Hipersensibilidade a Drogas/imunologia , Humanos , Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Valor Preditivo dos Testes , Fatores de Risco
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