RESUMO
The etiopathogenesis of potentially malignant oral disorders (PMOD) has not been fully understood yet. Recent results suggest that oxidative stress may be involved in the etiology of PMOD. Production of oxidants seems to be the major biological effect responsible for tissue injury and inflammatory response to air pollution. The aim of this study was to compare the oxidative stress markers and antioxidant potential in saliva of PMOD subjects and healthy controls in periods of high and low air pollution. Among enrolled 40 participants, there were 20 PMOD patients and 20 healthy volunteers. The exposure to air pollution was assessed by exhaled CO (eCO). Four oxidative status parameters: 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) were measured in saliva. Measurements were carried out in June (low air pollution) and November (increased air pollution). In both groups, significantly higher concentrations of 8-OHdG (P < 0.001 for PMOD patients and P = 0.001 for healthy controls), MDA (P = 0.002 and P = 0.012 respectively) and eCO (P < 0.001 and P < 0.001 respectively) were observed in periods of high air pollution. The concentration of TAC did not change between visits. The concentration of salivary GSH (P < 0.001 and P < 0.001 for both groups) decreased when compared between consecutive visits. We conclude that exhaled carbon monoxide (reflecting exposure to air pollution) correlated with the oxidative stress markers in patients with PMOD and healthy controls.
Assuntos
Poluição do Ar , Monóxido de Carbono/metabolismo , Exposição Ambiental , Doenças da Boca/metabolismo , Estresse Oxidativo , Saliva/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Biomarcadores/metabolismo , Testes Respiratórios , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Expiração , Feminino , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , PolôniaRESUMO
BACKGROUND AND AIMS: Treatment of severe peripheral arterial occlusive disease requires percutaneous revascularization. However, little is known about risk factors or predictors for reocclusion/restenosis. Cysteinyl leukotrienes are highly bioactive lipid mediators of inflammation. Their intravascular production may take place in the atheromatous plaque or result from interaction within activated leukocyte-platelet aggregates. METHODS: We prospectively measured urinary leukotriene E4, the main end-metabolite of cysteinyl leukotrienes in a group of 179 subjects with peripheral artery occlusive disease of the lower extremities. At the enrollment to the study, 22.9% had angioplasty and the remaining had angioplasty with stent implantation. During 12-month follow-up, 29.6% developed reocclusion/restenosis despite a standard pharmacotherapy. We evaluated treatment outcomes at 1, 3, 6 and 12-month follow-up visits, along with urinary leukotriene E4 excretion. RESULTS: During the study period, we observed a linear increase of urinary leukotriene E4 excretion only in subjects whose lower limb ischemia worsened. Moreover, elevated leukotriene E4 in urine was found only in subjects who developed reocclusion/restenosis. This was significant not only as a coincidence at the time of the follow-up visit, but leukotriene E4 elevation preceded clinical manifestation of reocclusion/restenosis. CONCLUSIONS: Our results demonstrated that serial measurements of urinary leukotriene E4 allowed to predict failure of angioplasty with/or without stent implantation for peripheral artery occlusive disease. However, to prove causality between cysteinyl leukotrienes overproduction and occlusive lower limb ischemia, a clinical trial with leukotrienes modifying drugs would be required.
Assuntos
Angioplastia , Arteriopatias Oclusivas/terapia , Cisteína/urina , Leucotrienos/urina , Doença Arterial Periférica/terapia , Idoso , Biomarcadores/metabolismo , Reestenose Coronária , Feminino , Seguimentos , Humanos , Isquemia , Leucotrieno E4/metabolismo , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. The specific role of induced sputum supernatant (ISS) endogenous bioactive lipid mediators in subtypes of asthma is not well understood. OBJECTIVE: To investigate the interactions between airway inflammation and clinical phenotypes of asthma, we integrated induced sputum supernatant (ISS) eicosanoids and quantitative assessment of infiltrating cells into new subtypes with the means of latent class analysis (LCA). METHODS: One hundred and thirty-nine asthmatics with and without aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids. Nineteen variables covering clinical characteristics, IS inflammatory cells and eicosanoids were considered in the LCA. RESULTS: Four phenotypic asthma classes were distinguished. Class 1 with mild-to-moderate asthma, chronic rhinosinusitis (CRS), high PGA2 in ISS and almost equal distribution of inflammation cell patterns. Class 3 subjects also had mild-to-moderate asthma but without upper airway symptoms. Induced sputum was often paucigranulocytic with low levels of lipid mediators. Classes 2 and 4 represented severe asthma with CRS and impaired lung function despite high doses of steroids. High blood and sputum eosinophilia was in line with high cysteinyl leukotrienes and PGD2 in ISS only in class 2. Class 4 subjects tended to have increased sputum neutrophilia and PGE2 in ISS. Aspirin hypersensitivity was most frequent among class 2 subjects. CONCLUSIONS & CLINICAL RELEVANCE: The LCA revealed four distinct asthma classes differing in eicosanoid pathways.
Assuntos
Asma/diagnóstico , Asma/metabolismo , Mediadores da Inflamação/metabolismo , Lipídeos/química , Escarro/química , Adulto , Asma/tratamento farmacológico , Asma/etiologia , Cromatografia Líquida , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Fenótipo , Testes de Função Respiratória , Fatores de RiscoRESUMO
BACKGROUND: Altered metabolism of eicosanoids is a characteristic finding in aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysyl-aspirin can be used as a confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. OBJECTIVES: To investigate the influence of inhaled lysyl-aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls. METHODS: Induced sputum was collected before and following bronchial challenge with lysyl-aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5-,12-,15-hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4 , 11-dehydro-thromboxane B2 , and prostaglandins E2 , D2 , and F2α and their metabolites, were measured using validated methods of chromatography-mass spectrometry. RESULTS: Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4 ) and leukotriene E4 (LTE4 ) concentrations. LTC4 , PGE2 , and 11-dehydro-TXB2 did not differ between the groups, but levels of LTD4 , LTE4 , and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only. CONCLUSIONS: During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin.
Assuntos
Asma Induzida por Aspirina/imunologia , Asma Induzida por Aspirina/metabolismo , Eicosanoides/metabolismo , Escarro/metabolismo , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/tratamento farmacológico , Testes de Provocação Brônquica , Progressão da Doença , Hipersensibilidade a Drogas , Volume Expiratório Forçado , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Leucotrienos/metabolismo , Pessoa de Meia-Idade , Prostaglandinas/metabolismo , Testes de Função Respiratória , Escarro/citologiaRESUMO
Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS(2)) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.