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1.
PLoS One ; 7(10): e47971, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23094102

RESUMO

The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Blattellidae/química , Misturas Complexas/imunologia , Inflamação/imunologia , Proteínas de Insetos/imunologia , Macrófagos Alveolares/imunologia , Serina Proteases/imunologia , Fator de Necrose Tumoral alfa/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Administração Intranasal , Alérgenos/farmacologia , Animais , Asma/induzido quimicamente , Asma/metabolismo , Asma/patologia , Blattellidae/enzimologia , Linhagem Celular , Misturas Complexas/química , Misturas Complexas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Imunoglobulina E/sangue , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Proteínas de Insetos/farmacologia , Interleucina-13/sangue , Interleucina-5/sangue , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Receptor PAR-2/genética , Receptor PAR-2/imunologia , Serina Proteases/farmacologia , Inibidores de Serina Proteinase/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
2.
Pharmacoepidemiol Drug Saf ; 20(1): 99-104, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20575103

RESUMO

PURPOSE: To evaluate the prevalence, compliance, pattern of use, and economic cost of OM in Korean allergy patients. METHODS: A total of 647 allergy patients were enrolled from 10 general hospitals, and were surveyed by the questionnaire. It consisted of 12 items and regarded the prescription rates, reasons for referring, their opinions for the efficacy of OM, and economic costs. RESULTS: A total of 259 (40.5%) patients had used OM, and 35.5% of these patients experienced two or more kinds of these practices. A patients' income or education level did not affect the prescription rates of OM. Of the patients that used OM, 34.6% of them were satisfied with the effect of OM treatment, and 40.9% of them were inclined to continue with their OM treatments. The most frequent reasons for choosing OM were the patient's belief that OM can predispose 'allergic constitution to normal' (30.2%), worries about the possible adverse reactions of the long-term administration of the proven drugs (20.2%), and the safety of OM (15.6%). However, 18.9% of these patients experienced perceived adverse events to their OM treatment such as skin rashes, gastrointestinal discomfort, and hepatitis. The patients that have used OM spent on average $915 US dollars annually for OM treatment. CONCLUSIONS: Many Korean allergy patients are cliental to OM. Some patients experienced a satisfactory treatment effect from OM, however, others had no treatment effect, even adverse event. Therefore, it is important to educate people to use OM appropriately to make harmony with modern medicine.


Assuntos
Hipersensibilidade/tratamento farmacológico , Medicina Tradicional do Leste Asiático , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Medicina Tradicional do Leste Asiático/efeitos adversos , Medicina Tradicional do Leste Asiático/economia , Pessoa de Meia-Idade , República da Coreia , Inquéritos e Questionários , Adulto Jovem
3.
Pharmacoepidemiol Drug Saf ; 18(10): 910-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19621345

RESUMO

PURPOSE: Patterns of prescriptions are markedly influenced by regional disease entities, medical education, culture, economic status, and available pharmaceutical companies. Features of adverse drug reactions (ADRs) may vary in different countries. In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea. METHODS: Six Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%). RESULTS: Based upon the World Health Organization (WHO)-Uppsala Monitoring Center criteria (certain-13.7%, probable-46.1%, possible-32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.1%), anti-psychotics (5.4%), anti-convulsants (5.2%), cardiovascular agents (4.8%), anti-neoplastics (4.6%), and opiates and non-opiate pain killers (3.5%). Among the antibiotics, cephalosporins (8.1%) were the most common, followed by anti-tuberculosis agents (5.7%), quinolones (4.0%), vancomycin (3.1%), and penicillin (2.8%). The most common side effect was skin manifestations, which were seen in 42% of the patients, followed by neurologic manifestations (14%), gastrointestinal involvements (12.9%), generalized reactions (9.4%), and respiratory involvements (4.5%). CONCLUSION: Antibiotics, contrast dyes, and NSAIDs were the most common causative drugs for ADRs, which reflects the prescription pattern and the prevalence of diseases in Korea. These data may be useful in establishing a Korean pharmacovigilance system.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Criança , Pré-Escolar , Meios de Contraste/efeitos adversos , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , República da Coreia , Medição de Risco , Fatores de Risco , Adulto Jovem
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