RESUMO
BACKGROUND: The impact of air pollution on the respiratory system has been estimated on the basis of respiratory symptoms and lung function. However; few studies have compared lung inflammation in healthy and asthmatics children exposed to high levels of air pollution. The aim of the study was to elucidate the modulatory effect of air pollution on Cysteinyl-leukotrienes (Cys-LTs) levels in exhaled breath condensate (EBC) among healthy and asthmatic children. METHODS: We performed a cross-sectional comparative study. Children between 7-12 years of age, asthmatics and non-asthmatics, residents of a city with high levels of PM10 were included. In all cases, forced spirometry, Cys-LTs levels in EBC, and the International Study of Asthma and Allergies in Childhood questionnaire were evaluated. We also obtained average of PM10, CO, SO2 and O3 levels during the period of the study by the State Institute of Ecology. RESULTS: We studied 103 children (51 asthmatics and 52 non-asthmatics). Cys-LTs levels were higher in asthmatics than in non-asthmatics (77.3 ± 21.6 versus 60.3 ± 26.8 pg/ml; p = 0.0005). Also, Cys-LTs levels in children with intermittent asthma were lower than in children with persistent asthma (60.4 ± 20.4 versus 84.7 ± 19.2 pg/ml; p = 0.0001). In the multiple regression model, factors associated with levels of Cys-LTs were passive smoking (ß = 13.1, p 0.04) and to be asthmatic (ß = 11.5, p 0.03). CONCLUSIONS: Cys-LTs levels are higher in asthmatic children than in healthy children in a contaminated city and its levels are also associated with passive smoking.
Assuntos
Poluição do Ar , Asma/metabolismo , Mediadores da Inflamação/análise , Material Particulado , Pneumonia/metabolismo , População Urbana , Asma/complicações , Asma/fisiopatologia , Testes Respiratórios , Criança , Estudos Transversais , Feminino , Volume Expiratório Forçado , Voluntários Saudáveis , Humanos , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Masculino , Pneumonia/complicações , Espirometria , Inquéritos e Questionários , Poluição por Fumaça de Tabaco , Capacidade VitalRESUMO
A sensitive and precise method for simultaneous quantification of cysteinyl leukotrienes (=cys LTs) - leukotriene C4 (=LTC4), leukotriene D4 (=LTD4) and leukotriene E4 (=LTE4) - essential biomarkers of bronchial asthma present in exhaled breath condensate (=EBC) was developed. An immunomagnetic molecular probe was prepared by anchoring cysteinyl leukotrienes antibody on the surface of functionalized monodispersed magnetic particles and used to selectively isolate cys LTs from biological matrices - EBC, plasma and urine. Immobilization and the immunoaffinity capture procedures were optimized to maximize the amount of separated cys LTs, which were detected "off-beads" after acidic elution by UHPLC-ESI-MS/MS operated in a multiple reaction monitoring mode. The developed method was characterized with high precision ≤13.6% (intra-day precision determined as RSD) and ≤14.5% (inter-day precision determined as RSD), acceptable accuracy ≤18.5% (determined as RE), and high recovery of immunoseparation (≥93.1%) in aforementioned biological matrices. The applicability of the method was demonstrated on EBC, plasma and urine clinical samples of patients with various subtypes of bronchial asthma (occupational, steroid-resistant, moderate with and without corticosteroids therapy) and healthy subjects where reasonable differences in cys LTs concentration levels were found. Combining extremely selective immunomagnetic separation with highly sensitive and precise detection step, the developed method was used to aid diagnosis, predict the most effective therapy, and monitor the response to treatment. The detection of elevated inflammatory mediators (cys LTs) in EBC of subjects with relatively asymptomatic asthma and normal pulmonary function tests could offer a novel way for monitoring the lung inflammation and perhaps initiating treatment in an earlier stage.
Assuntos
Asma/diagnóstico , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Asma/tratamento farmacológico , Asma/fisiopatologia , Testes Respiratórios , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Glucocorticoides/uso terapêutico , Humanos , Separação Imunomagnética/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
BACKGROUND: Cysteinyl leukotrienes (CysLTs) are among important inflammatory mediators in asthma pathogenesis. In this study, we aimed to determine leukotriene D4 (LTD4) and leukotriene E4 (LTE4) levels in exhaled breath condensate (EBC) in asthmatics and to evaluate the effect of smoking upon CysLTs levels and to speculate the importance of adding leukotriene receptor antagonists in smoking asthmatics. METHODS: A total of 88 participants were included in the study. Of them, 59 were asthmatics; 30 of the 59 asthmatics were smokers (Group I) and the others were non-smokers (Group II). As a control group (Group III), 29 healthy non-smokers were enrolled. EBC samples were collected (EcoScreen, Jaeger, Hoechberg, Germany) and pulmonary function tests (PFTs) were performed in each case, and an asthma control questionnaire (ACQ) was completed by the asthmatics. LTD4 and LTE4 levels in EBC samples were analyzed by using ELISA. RESULTS: LTD4 levels were found to be higher in Group I than other groups and similar in Group II and Group III. LTE4 levels were lower in Group III than other groups and similar in Group I and Group II. PFTs were different between Group I and Group III and there was a significant negative correlation between LTE4 levels and forced expiratory volume in one second and forced vital capacity ratio in Group I. CONCLUSIONS: LTD4, but not LTE4, concentrations in EBC were higher in asthmatic smokers than asthmatic nonsmokers. LTE4 concentrations in EBC were higher in asthmatics than healthy non-smokers. In smoking asthmatics usage of agents that block the effects of LTD4 can be beneficial; however, new clinical studies are required.
Assuntos
Asma , Testes Respiratórios , Cisteína/análise , Expiração , Leucotrieno D4/análise , Leucotrienos/análise , Fumar , Adulto , Asma/tratamento farmacológico , Estudos de Casos e Controles , Testes de Química Clínica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Receptores de Leucotrienos/metabolismo , Testes de Função Respiratória , Fumar/tratamento farmacológico , Inquéritos e Questionários , Adulto JovemRESUMO
Leukotrienes (LTs) are involved in the pathogenesis of lung fibrosis and were increased in exhaled breath condensate (EBC) of the patients with pneumoconiosis. However the possible influence of extra-pulmonary disorders on the EBC markers is not known. Therefore in parallel with EBC, LTs' levels in the plasma and urine were measured in patients with pneumoconiosis (45 × asbestos exposure, 37 × silica exposure) and in 27 controls. Individual LTs B4, C4, D4 and E4 were measured by liquid chromatography - electrospray ionization - tandem mass spectrometry (LC-ESI-MS/MS). In EBC, LT D4 and LT E4 were increased in both groups of patients (p<0.001 and p<0.05), comparing with the controls. Both LT B4 and cysteinyl LTs were elevated in asbestos-exposed subjects (p<0.05). Asbestosis with more severe radiological signs (s1/s2-t3/u2) and lung functions impairment has shown higher cysteinyl LTs and LT C4 in the EBC (p<0.05) than mild asbestosis (s1/s0-s1/s1). In addition, in the subjects with asbestosis, cysteinyl LTs in EBC correlated with TLC (-0.313, p<0.05) and TLCO/Hb (-0.307, p<0.05), and LT C4 with TLC (-0.358, p<0.05). In pneumoconioses, EBC appears the most useful from the 3 fluids studied.
Assuntos
Asbestose/metabolismo , Testes Respiratórios , Leucotrienos/análise , Silicose/metabolismo , Idoso , Asbestose/diagnóstico por imagem , Feminino , Humanos , Leucotrieno B4/análise , Leucotrieno B4/sangue , Leucotrieno B4/urina , Leucotrieno C4/análise , Leucotrieno C4/sangue , Leucotrieno C4/urina , Leucotrieno D4/análise , Leucotrieno D4/sangue , Leucotrieno D4/urina , Leucotrieno E4/análise , Leucotrieno E4/sangue , Leucotrieno E4/urina , Leucotrienos/sangue , Leucotrienos/urina , Masculino , Pessoa de Meia-Idade , Radiografia , Testes de Função Respiratória , Índice de Gravidade de Doença , Silicose/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the changes of leukotriene D4 (LTD4) in nasal discharge and plasma of patients with persistent allergic rhinitis (AR) and the effects of antihistamine. METHOD: The investigation was a prospective, randomized controlled trial. Forty AR patients (group C) were divided randomly into two subgroup. One group received oral antihistamine 10 mg everyday for one week (group CA) and another group received no loratadine tablets 10 mg everyday for one week (group CB). Fifteen age matched healthy (group D) people were enrolled as control. The level of LTD4 and interleukin-5 (IL-5) in both nasal discharge and plasma by using enzyme linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), cell counts and cell differentials in nasal discharge, were measured before and after three month. The clinical symptom and life quality scores of group C were also investigated. RESULT: The concentrations of LTD4 in nasal discharge [(794 +/- 305) pg] and plasma [(5219 +/- those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P 1185) ng/L] in group C were significantly higher than those in group D [(347 +/- 169) pg, (2283 +/- 489) ng/L, all P < 0.05]. The level of LTD4 in nasal discharge was positively correlated with the percentage of neutrophil (r = 0.453, P < 0.05) and IL-5 (r = 0.364, P < 0.05). The pre- and post-therapy concentrations of nasal discharge and plasma in group CA were (812 +/- 1592) pg, (657 +/- 495) pg and (5422 +/- 935) ng/L, (4589 +/- 1057) ng/L respectively; While in group CB the concentrations were (776 +/- 227) pg, (860 +/- 194) pg and (5074 +/- 1850) ng/L, (6063 +/- 450) ng/L, respectively. There were no significant difference either in the level of LTD4 in nasal discharge or in plasma in both groups (all P > 0.05). CONCLUSION: The results suggested that LTD4 was involved in airway inflammation in AR. Antihistamine was not effective enough in decreasing the levels of LTD4 in both nasal discharge and plasma of AR patients.
Assuntos
Antagonistas de Leucotrienos/uso terapêutico , Leucotrieno D4/análise , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Perene/metabolismo , Adulto , Antialérgicos/farmacologia , Secreções Corporais/química , Feminino , Antagonistas dos Receptores Histamínicos H1/farmacologia , Humanos , Leucotrieno D4/sangue , Leucotrieno D4/metabolismo , Masculino , Pessoa de Meia-Idade , Plasma/química , Estudos Prospectivos , Rinite Alérgica Perene/sangueRESUMO
OBJECTIVE: Allergic rhinitis, a disease that impairs quality of life, is characterized by inflammation due to an allergic reaction. Fexofenadine is a second-generation histamine receptor blocker well known for its potent interaction with this inflammatory process. The main aim of this study was to further clarify the anti-inflammatory effects exerted by fexofenadine in patients with intermittent allergic rhinitis. METHODS: Twenty patients with intermittent allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was administered once a day at a dose of 120 mg. Clinical improvement was assessed by a symptom score, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were tested for eosinophils and nasal lavage fluid were examined for histamine, cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests were performed during the pollen season. RESULTS: Fexofenadine induced a significant improvement in nasal and ocular symptoms (P < .001), nasal edema and secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement was related to a significant reduction in all inflammatory mediators (P < .01 in all cases). CONCLUSION: This study demonstrates that fexofenadine is able to mediate significant changes in different nasal lavage markers from patients with intermittent allergic rhinitis. The changes observed in the markers analyzed in both nasal secretions and serum are attributable to the anti-inflammatory effects of fexofenadine in vivo.
Assuntos
Anti-Inflamatórios/administração & dosagem , Mediadores da Inflamação/imunologia , Líquido da Lavagem Nasal/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Terfenadina/análogos & derivados , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Antígenos de Plantas/efeitos adversos , Antígenos de Plantas/imunologia , Artemisia/imunologia , Betula/imunologia , Progressão da Doença , Proteína Catiônica de Eosinófilo/análise , Feminino , Histamina/análise , Humanos , Mediadores da Inflamação/análise , Molécula 1 de Adesão Intercelular/análise , Leucotrieno D4/análise , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/química , Pólen/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Terfenadina/administração & dosagem , Terfenadina/efeitos adversos , Resultado do TratamentoAssuntos
Criopreservação/métodos , Pulmão , Preservação de Órgãos/métodos , Anafilaxia/imunologia , Anafilaxia/metabolismo , Anticorpos Anti-Idiotípicos/farmacologia , Criopreservação/instrumentação , DNA de Cadeia Simples/análise , Humanos , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/ultraestrutura , Transplante de Pulmão , Preservação de Órgãos/instrumentação , Pneumonectomia , Eletricidade Estática , Coleta de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos , Transplante HomólogoRESUMO
PURPOSE: To ensure the suitable preservation of isolated lungs, a super-cooling system was used to cool water to temperatures as low as -5 degrees C without freezing. DESCRIPTION: After lung tissues were obtained from patients with lung cancer, they were kept at -5 degrees C or 4 degrees C for as many as 5 days, and then they were histologically and biochemically examined. To evaluate biochemical stability, tissues after storage were passively sensitized with immunoglobulin E and then incubated with anti-immunoglobulin-E antibody. EVALUATION: Although tissues preserved at -5 degrees C for 5 days had an almost normal appearance with intact cilia on bronchial epithelium and normal endothelium, tissues stored at 4 degrees C showed degradation of these structures. Single-stranded DNA, a sign of DNA cleavage, was frequently noted in tissues stored at 4 degrees C, but only rarely observed at -5 degrees C. A significant amount of cysteinyl-leukotrienes was generated from tissues stored at -5 degrees C for 3 days, but there was no response to antibody stimulation from tissues stored at 4 degrees C. CONCLUSIONS: Super-cooling systems may provide useful applications as a novel preserving method.
Assuntos
Criopreservação/métodos , Pulmão , Preservação de Órgãos/métodos , Idoso , Idoso de 80 Anos ou mais , Anafilaxia/imunologia , Anafilaxia/metabolismo , Anticorpos Anti-Idiotípicos/farmacologia , Criopreservação/instrumentação , DNA de Cadeia Simples/análise , Feminino , Humanos , Soluções Hipertônicas , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/ultraestrutura , Neoplasias Pulmonares/química , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/ultraestrutura , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Soluções para Preservação de Órgãos , Pneumonectomia , Refrigeração/instrumentação , Eletricidade Estática , Temperatura , Coleta de Tecidos e ÓrgãosRESUMO
BACKGROUND: Viral respiratory tract infections represent the most frequent cause of asthma exacerbation in both children and adults, but the precise mechanism of such exacerbation remains unknown. OBJECTIVES: To determine the critical mediator of naturally occurring parainfluenza virus (PIV) 3-induced mild asthma exacerbations in adults. METHODS: The study subjects were 19 adult asthmatics with mild asthma exacerbation (peak expiratory flow = 60-80% of predicted before bronchodilator use and >80% of predicted after initial bronchodilator treatment). Differential cell counts and concentrations of inflammatory markers including eosinophil cationic protein (ECP), cysteinyl leukotrienes (cysLTs), interleukin (IL)-5, IL-10 and IL-12 were measured in the induced sputum obtained from adults with PIV3- (n = 9) and non-cold-induced (n = 10) exacerbation of asthma during both acute and convalescent phases. RESULTS: PIV3 infection was confirmed by the presence of viral RNA in nasopharyngeal aspirates. Mild exacerbation of asthma was not associated with significant changes in sputum differential cell counts. Concentrations of sputum ECP and cytokines were comparable between PIV3 and non-cold-induced patients. In contrast, PIV3 infection was associated with a significant increase in sputum cysLTs during the acute phase of mild asthma exacerbation. CONCLUSIONS: Our results identified cysLTs as a critical mediator of PIV3-induced acute asthma exacerbation.
Assuntos
Asma/virologia , Leucotrieno D4/análise , Vírus da Parainfluenza 3 Humana , Infecções por Respirovirus/complicações , Escarro/imunologia , Adulto , Asma/imunologia , Citocinas/análise , Proteína Catiônica de Eosinófilo/análise , Feminino , Humanos , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Recidiva , Escarro/citologiaRESUMO
BACKGROUND: After in vitro allergen-specific stimulation, basophils become activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be detected by means of the CAST assay. We assessed the positivity criteria and the reliability of antigen-specific sulfidoleukotriene production (CAST) in the in vitro diagnosis of betalactam (BL) allergic patients. MATERIAL AND METHODS: We studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented with anaphylaxis or urticaria-angioedema within the first 60 minutes after administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or Cefazoline (1/67). All of them had a positive skin test to at least one of the antigenic determinants of Penicillin. As control group 30 adults with negative skin tests who tolerated BL were included. All of them underwent skin tests, oral provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST. RESULTS: Positivity criteria were established by means of ROC curves: a sLT release induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%. Sensitivity of specific IgE is 37.8% and specificity 83.3%. CONCLUSIONS: We have established validated positivity criteria for the CAST technique in patients allergic to Betalactams. This technique is a useful in vitro diagnostic method in patients with IgE-mediated allergy to Betalactam antibiotics.
Assuntos
Antibacterianos/imunologia , Hipersensibilidade a Drogas/imunologia , Lactamas/imunologia , Leucotrienos/análise , Amoxicilina/efeitos adversos , Amoxicilina/imunologia , Anafilaxia/imunologia , Angioedema/imunologia , Antibacterianos/efeitos adversos , Cefazolina/efeitos adversos , Cefazolina/imunologia , Cefuroxima/efeitos adversos , Cefuroxima/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Lactamas/efeitos adversos , Leucotrieno C4/análise , Leucotrieno C4/imunologia , Leucotrieno D4/análise , Leucotrieno D4/imunologia , Leucotrieno E4/análise , Leucotrieno E4/biossíntese , Leucotrienos/imunologia , Masculino , Pessoa de Meia-Idade , Penicilina G/efeitos adversos , Penicilina G/imunologia , Testes Cutâneos , Urticária/imunologiaRESUMO
OBJECTIVE: To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. ANIMALS: 19 cats with experimentally induced asthma and 5 control cats. PROCEDURE: Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. RESULTS: Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. CONCLUSIONS AND CLINICAL RELEVANCE: Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.
Assuntos
Asma Induzida por Exercício/veterinária , Líquido da Lavagem Broncoalveolar/química , Doenças do Gato/fisiopatologia , Cisteína , Leucotrienos/análise , Animais , Asma Induzida por Exercício/fisiopatologia , Asma Induzida por Exercício/urina , Doenças do Gato/urina , Gatos , Ensaio de Imunoadsorção Enzimática , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Leucotrienos/urinaRESUMO
Acute respiratory distress syndrome (ARDS) is an acute lung injury of high mortality rate, and sepsis syndrome is one of the most frequent causes of ARDS. Metabolites of arachidonic acid, including thromboxanes and leukotrienes, are proinflammatory mediators and potentially involved in the development of ARDS. A key enzyme for the production of these inflammatory mediators is cytosolic phospholipase A(2) (cPLA(2)). Recently, it has been reported that arachidonyl trifluoromethyl ketone (ATK) is a potent inhibitor of cPLA(2). In the present study, we hypothesized that pharmacological intervention of cPLA(2) could affect acute lung injury. To test this hypothesis, we examined the effects of ATK in a murine model of acute lung injury induced by septic syndrome. The treatment with ATK significantly attenuated lung injury, polymorphonuclear neutrophil sequestration, and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. The current observations suggest that pharmacological intervention of cPLA(2) could be a novel therapeutic approach to acute lung injury caused by sepsis syndrome.
Assuntos
Ácidos Araquidônicos/farmacologia , Inibidores Enzimáticos/farmacologia , Fosfolipases A/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citosol/enzimologia , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Lipopolissacarídeos , Pulmão/enzimologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Fosfolipases A2 , Síndrome do Desconforto Respiratório/induzido quimicamente , Sepse/induzido quimicamente , Sepse/tratamento farmacológico , Sepse/metabolismo , Cloreto de Sódio , Tromboxano B2/análise , ZimosanRESUMO
BACKGROUND: Cysteinyl leukotrienes (LTs) are potent proinflammatory mediators. They are predominantly excreted from blood by hepatobiliary elimination. To explore the clinical significance of biliary cysteinyl LTs, we determined their concentration changes in bile during treatment in patients with obstructive jaundice. METHODS: Bile samples were obtained during endoscopic or transhepatic biliary drainage. Leukotrienes C(4), D(4), and E(4) were quantified by two-step reversed-phase high-performance liquid chromatography and subsequent radioimmunoassay. RESULTS: The increased excretion of cysteinyl LTs (LTC(4) + LTD(4) + LTE(4)) decreased between day 1 and 14 after drainage (means, 171 pmol/h to 79 pmol/h; P < 0.02). During drainage, the excretion was higher when there was additional cholangitis (mean, 225 and 86 pmol/h, with and without cholangitis, respectively; P < 0.001). The concentrations of LTD(4) and LTE(4) were also higher with additional cholangitis than without (LTD(4), mean 6.0 vs 2.0 nM; P < 0.05; LTE(4), 6.8 vs 2.4 nM; P < 0.02, respectively). Biliary LTC(4) was detected only in patients with cholangitis. The biliary excretion of cysteinyl LTs was positively correlated with leukocyte concentration ( r = 0.68; P < 0.005) and C-reactive protein ( r = 0.73; P < 0.005) in blood. Furthermore, only in the absence of cholangitis, the excretion was positively correlated with serum gamma-glutamyl transferase ( r = 0.76; P < 0.02) and alanine aminotransferase ( r = 0.72; P < 0.02). CONCLUSIONS: The excretion of biliary cysteinyl LTs increases with the severity of cholestasis and hepatic inflammation in patients with obstructive jaundice. An additional increase of cysteinyl LTs was observed during bacterial cholangitis. The increased biliary excretion of biologically active cysteinyl LTs may contribute to the aggravation of cholestasis and inflammatory reaction in obstructive jaundice.
Assuntos
Bile/química , Colestase/metabolismo , Leucotrieno E4/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Colestase/urina , Cromatografia Líquida de Alta Pressão , Cisteína , Feminino , Humanos , Leucotrieno C4/análise , Leucotrieno C4/urina , Leucotrieno D4/análise , Leucotrieno D4/urina , Leucotrieno E4/análise , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
BACKGROUND: Prostaglandin E2 is a potent immunomodulator that inhibits the early and late bronchoconstriction to inhaled allergen, as well as inhibiting the acute allergen-induced release of mediators into the human airway. To determine if the stable prostaglandin E agonist misoprostol could alter the late allergic formation of mediators we measured the appearance of eosinophils and key cytokines in the bronchoalveolar lavage fluid 24 h after allergen instillation. METHODS: Six atopic asthmatics underwent bronchoscopy, alveolar lavage and antigen instillation followed 24 h later by bronchoalveolar lavage. Eosinophil counts were done, together with measurements of IL-4, IL-5, eotaxin, RANTES and cysteinyl leukotrienes by immunoassay. The study was done in randomized blinded fashion while the volunteers took placebo or 600 microg of misoprostol four times a day (QID). RESULTS: Misoprostol significantly decreased the appearance of IL-5 late after allergen challenge. Eotaxin levels were reduced, but not statistically significantly. Eosinophil number, RANTES, eosinophil cationic protein and cysteinyl leukotrienes were not altered by misoprostol. CONCLUSIONS: Misoprostol reduces the formation of IL-5 late after allergen challenge, perhaps by inhibiting eosinophil, mast cell, and/or T lymphocyte production of IL-5. Despite decreases in IL-5 and eotaxin, eosinophils were recruited and activated by allergen.
Assuntos
Asma/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Interleucina-5/biossíntese , Misoprostol/uso terapêutico , Ribonucleases , Adulto , Asma/fisiopatologia , Proteínas Sanguíneas/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CCL11 , Quimiocinas CC/análise , Proteínas Granulares de Eosinófilos , Eosinófilos , Humanos , Hipersensibilidade Imediata/fisiopatologia , Leucotrieno D4/análise , Pessoa de Meia-Idade , Misoprostol/administração & dosagem , Misoprostol/farmacologiaRESUMO
Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between the upregulation of cellular immunity with IL-2 and the LT pathway in ovalbumin-sensitized BN rats. Airway responsiveness to LTD(4) was significantly increased in BN rats pretreated with IL-2 (20,000 U twice a day for 4.5 days). Treatment with montelukast, a cysteinyl LT(1) receptor antagonist, blocked IL-2's induced increase of the LR to ovalbumin challenge. When cytokine expression was assessed either by semiquantitative polymerase chain reaction or in situ hybridization, we found that montelukast decreased the amount of IL-4 mRNA expression in the lungs while increasing the amount of interferon-gamma mRNA expression 8 hours after challenge. These results indicate that upregulation of cellular immunity with IL-2 can increase the sensitivity of the airways to LTD(4) and that inhibition of the LT pathway will block the LR and modulate cytokine expression after antigen challenge.
Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/imunologia , Interleucina-2/farmacologia , Leucotrieno D4/metabolismo , Células Th2/imunologia , Análise de Variância , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Imunidade Celular/efeitos dos fármacos , Hibridização In Situ , Interferon gama/análise , Interferon gama/metabolismo , Leucotrieno D4/análise , Masculino , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos BN , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Regulação para CimaRESUMO
Inhalation of heparin attenuates hyperventilation-induced bronchoconstriction in humans and dogs. The purpose of this study was to determine whether heparin inhibits the late-phase response to hyperventilation, which is characterized by increased peripheral airway resistance (RP), eicosanoid mediator production, neutrophilic/ eosinophilic inflammation, and airway hyperreactivity (AHR) at 5 h after dry air challenge (DAC). Fiberoptic bronchoscopy was used to record RP and airway reactivity (DeltaRP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured approximately 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (approximately 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C(4), LTD(4), and LTE(4) and prostaglandin (PG)D(2), and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by approximately 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC(4), LTD(4), and LTE(4) and PGD(2), and abolished AHR. We conclude that heparin inhibits hyperventilation-induced late-phase changes in peripheral airway function, and does so in part via the inhibition of eosinophil migration and eicosanoid mediator production and release.
Assuntos
Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/prevenção & controle , Modelos Animais de Doenças , Heparina/uso terapêutico , Hiperventilação/complicações , Administração por Inalação , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Broncoscopia , Cães , Avaliação Pré-Clínica de Medicamentos , Eicosanoides/imunologia , Eicosanoides/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Heparina/farmacologia , Humanos , Hiperventilação/imunologia , Hiperventilação/metabolismo , Hiperventilação/fisiopatologia , Inflamação , Leucotrieno C4/análise , Leucotrieno D4/análise , Leucotrieno E4/análise , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Prostaglandina D2/análise , Fatores de TempoRESUMO
BACKGROUND: Leukotrienes (LTs) are important in asthma, and LT modifiers modulate antigen-induced asthma. Overproduction of LT by suppression of cyclooxygenase activity is involved in patients with aspirin-intolerant asthma (AIA). METHODS: House dust mite (HDM) inhalation provocation tests were performed in HDM-sensitive asthmatic inpatients without AIA (HDM group; n = 6), and aspirin oral provocation tests were performed in AIA patients (ASA group; n = 7). Tests were repeated using the same regimen after 7 days of treatment with pranlukast, an LT receptor antagonist (LTRA). The effects of pranlukast on changes in sputum LTC(4)-LTD(4), eosinophil cationic protein (ECP), eosinophil count, urinary LTE(4)/creatinine, 11-dehydrothromboxane B(2) (11-dhTXB(2))/creatinine, serum LTC(4)-LTD(4), ECP, and peripheral blood eosinophil count, during immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) in the HDM group and during IAR in the ASA group for each test, were compared in each group. RESULTS: In the HDM group, IAR and LAR were observed. Sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine increased significantly both during IAR and LAR. Sputum ECP increased during IAR and further increased during LAR. Eosinophil count in the sputum did not increase during IAR but significantly increased during LAR. Pranlukast suppressed the fall in FEV(1) both during IAR and LAR (73.8% and 51.9%, respectively) and inhibited the increase in sputum eosinophil count during LAR and sputum ECP during IAR and LAR. In the ASA group, aspirin-induced IAR was associated with a fall in urinary 11-dhTXB(2)/creatinine, increased the levels of sputum LTC(4)-LTD(4) and ECP and urinary LTE(4)/creatinine. Pranlukast suppressed IAR and inhibited the increase of the level of sputum ECP, but failed to change aspirin-induced LT production in the sputum and urine. The levels of sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine in the stable phase in the ASA group were significantly greater than those in the HDM group. CONCLUSION: Our results indicated that HDM-provoked asthma is associated with overproduction of LT with an antigen-antibody reaction, while AIA is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade. LTRA may be useful against both types of asthma through inhibition of LT activity and eosinophilic inflammation of the airways.
Assuntos
Antiasmáticos/administração & dosagem , Aspirina/efeitos adversos , Asma/tratamento farmacológico , Testes de Provocação Brônquica , Cromonas/administração & dosagem , Hipersensibilidade a Drogas/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Contagem de Leucócitos , Leucotrieno D4/análise , Leucotrieno E4/análise , Ribonucleases , Tromboxano B2/análogos & derivados , Adulto , Antiasmáticos/efeitos adversos , Asma/imunologia , Proteínas Sanguíneas/análise , Cromonas/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Proteínas Granulares de Eosinófilos , Eosinófilos/imunologia , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tromboxano B2/análiseRESUMO
BACKGROUND: Allergic rhinitis is an IgE mediated hypersensitivity reaction of the nasal mucosa characterised by nasal discharge, obstruction, and pruritus. PATIENTS AND METHODS: In this study, 43 patients with perenneal allergic rhinitis were enrolled in order to compare the efficacy of Fluticasone Propionate (FP), a corticosteroid nasal spray, with Cetirizine, a systemic oral antihistaminic preparation, which is supposed to have nonsteroidal antiinflammatory activity. Cetirizine (10 mg daily as a single dose) was administered to 22 patient for 45 days. On the other hand, FP (400 micrograms/day) was administered into each nostril twice a day in the remaining 21 patients for 45 days. Skin test was obtained from each patient before therapy. Total eosinophil count, eosinophil count in nasal smear, electrorhinomanometric investigation, PGE2 and ratio of LTC4 to LTD4 both in the serum and in the nasal secretions were determined before and after therapy. In addition, percentage of eosinophils, and mast cells count in the biopsy specimens taken from anterior edge of middle choncha were evaluated before and after therapy, and than the results were graded for each patients. RESULTS: When we compared the eosinophil count in nasal smear, eosinophil percentage and total eosinophil parameters between two groups, it was shown that FP was more effective than Cetirizine. On the other hand, when we compared the ratio of LTC4 to LTD4 in serum and nasal smear, level of PGE2 and mast cell and nasal airway resistance measured by ERM, there were non statistical difference between two groups. CONCLUSION: These results suggest that FP and Cetirizine may be used alternatively in case of an adverse reaction to any of them.