ABSTRACT
The free radical nitric oxide (·NO) is a key mediator in different physiological processes such as vasodilation, neurotransmission, inflammation, and cellular immune responses, and thus preserving its bioavailability is essential. In several disease conditions, superoxide radical (O2·-) production increases and leads to the rapid "inactivation" of ·NO by a diffusion-controlled radical termination reaction that yields a potent and short-lived oxidant, peroxynitrite. This reaction not only limits ·NO bioavailability for physiological signal transduction but also can divert and switch the biochemistry of ·NO toward nitrooxidative processes. Indeed, since the early 1990s peroxynitrite (and its secondary derived species) has been linked to the establishment and progression of different acute and chronic human diseases and also to the normal aging process. Here, we revisit an earlier and classical review on the role of peroxynitrite in human physiology and pathology (Pacher P, Beckman J, Liaudet L. Physiol Rev 87: 315-424, 2007) and further integrate, update, and interpret the accumulated evidence over 30 years of research. Innovative tools and approaches for the detection, quantitation, and sub- or extracellular mapping of peroxynitrite and its secondary products (e.g., protein 3-nitrotyrosine) have allowed us to unambiguously connect the complex biochemistry of peroxynitrite with numerous biological outcomes at the physiological and pathological levels. Furthermore, our current knowledge of the ·NO/O2·- and peroxynitrite interplay at the cell, tissue, and organ levels is assisting in the discovery of therapeutic interventions for a variety of human diseases.
Subject(s)
Peroxynitrous Acid , Superoxides , Biology , Humans , Nitric Oxide/metabolism , Peroxynitrous Acid/metabolismABSTRACT
Trypanosoma cruzi is a flagellated protozoan that undergoes a complex life cycle between hematophagous insects and mammals. In humans, this parasite causes Chagas disease, which in thirty percent of those infected, would result in serious chronic pathologies and even death. Macrophages participate in the first stages of infection, mounting a cytotoxic response which promotes massive oxidative damage to the parasite. On the other hand, T. cruzi is equipped with a robust antioxidant system to repeal the oxidative attack from macrophages. This work was conceived to explicitly assess the role of mammalian cell-derived superoxide radical in a murine model of acute infection by T. cruzi. Macrophages derived from Nox2-deficient (gp91phox-/-) mice produced marginal amounts of superoxide radical and were more susceptible to parasite infection than those derived from wild type (wt) animals. Also, the lack of superoxide radical led to an impairment of parasite differentiation inside gp91phox-/- macrophages. Biochemical or genetic reconstitution of intraphagosomal superoxide radical formation in gp91phox-/- macrophages reverted the lack of control of infection. Along the same line, gp91phox-/- infected mice died shortly after infection. In spite of the higher lethality, parasitemia did not differ between gp91phox-/- and wt animals, recapitulating an observation that has led to conflicting interpretations about the importance of the mammalian oxidative response against T. cruzi. Importantly, gp91phox-/- mice presented higher and disseminated tissue parasitism, as evaluated by both qPCR- and bioimaging-based methodologies. Thus, this work supports that Nox2-derived superoxide radical plays a crucial role to control T. cruzi infection in the early phase of a murine model of Chagas disease.
Subject(s)
Chagas Disease , Trypanosoma cruzi , Animals , Macrophages , Mice , Oxidative Stress , SuperoxidesABSTRACT
Aminoacetone (1-aminopropan-2-one), a putative minor biological source of methylglyoxal, reacts like other α-aminoketones such as 6-aminolevulinic acid (first heme precursor) and 1,4-diaminobutanone (a microbicide) yielding electrophilic α-oxoaldehydes, ammonium ion and reactive oxygen species by metal- and hemeprotein-catalyzed aerobic oxidation. A plethora of recent reports implicates triose phosphate-generated methylglyoxal in protein crosslinking and DNA addition, leading to age-related disorders, including diabetes. Importantly, methylglyoxal-treated hemoglobin adds four water-exposed arginine residues, which may compromise its physiological role and potentially serve as biomarkers for diabetes. This paper reports on the co-oxidation of aminoacetone and oxyhemoglobin in normally aerated phosphate buffer, leading to structural changes in hemoglobin, which can be attributed to the addition of aminoacetone-produced methylglyoxal to the protein. Hydroxyl radical-promoted chemical damage to hemoglobin may also occur in parallel, which is suggested by EPR-spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide and ethanol. Concomitantly, oxyhemoglobin is oxidized to methemoglobin, as indicated by characteristic CD spectral changes in the Soret and visible regions. Overall, these findings may contribute to elucidate the molecular mechanisms underlying human diseases associated with hemoglobin dysfunctions and with aminoacetone in metabolic alterations related to excess glycine and threonine.
Subject(s)
Hemoglobins , Pyruvaldehyde , Acetone/analogs & derivatives , Electron Spin Resonance Spectroscopy , Humans , Oxidation-Reduction , Reactive Oxygen SpeciesABSTRACT
This work reports a new method to evaluate the antioxidant capacity of infusions and beverages, based on superoxide radicals. Radicals produced by the enzymatic reaction between acetylcholinesterase and hypoxanthine oxidized antioxidant molecules present in commercially available samples or standard solutions, which was monitored by means of cyclic voltammetry using a carbon paste electrode. The Trolox equivalent antioxidant capacity (TEAC) of red wine, coffee and green tea determined using this method were: (1.20 ± 0.06), (0.90 ± 0.02), and (0.65 ± 0.02), respectively. This method suggested TEACred wine > TEACcoffee > TEACgreen tea, which is the same as DPPH, spectrophotometric method. However, the electrochemical one proposed here is rapid and simple.
Subject(s)
Antioxidants/chemistry , Beverages/analysis , Electrochemical Techniques/methods , Superoxides/chemistry , Antioxidants/metabolism , Coffee/chemistry , Electrodes , Hydrogen-Ion Concentration , Hypoxanthine/chemistry , Hypoxanthine/metabolism , Oxidation-Reduction , Superoxides/metabolism , Tea/chemistry , Wine/analysis , Xanthine Oxidase/metabolismABSTRACT
Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18-labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products.
Subject(s)
Boronic Acids/chemistry , Molecular Probes/chemistry , Molecular Probes/metabolism , Oxidants/chemistry , Oxidants/metabolism , Oxygen Isotopes/chemistry , Brain/metabolism , Isotope LabelingABSTRACT
Moringa oleifera Lam. has been considered as a multipurpose tree. The studies on it focus on its variable nutritional benefits. It is growing in many regions, but information about nutritional properties of those growing in the Caribbean is missing. The present study focused on biochemical analysis of main nutritional and antioxidant properties in plant material-dried leaves and seeds-of Moringa oleifera. The composition of lipids, proteins, and vitamin E was evaluated in powdered dried leaves and seeds. Fatty acids were evaluated in oil extracted from the moringa seeds. Potential antioxidant properties of the moringa were evaluated in extract from crushed and powdered leaves, as well as from the powdered seeds. The total amounts of lipids, proteins, and vitamin E were higher in powdered seeds (31.85%, 35.13%, and 220.61 mg/kg) than in powdered leaves (12.48%, 20.54%, and 178.10 mg/kg). The main compound of fatty acids presented oleic acid (76.78%) in seeds' oil and oleic (25.01%), palmitic (24.84%), and linolenic (24.71%) acids in leaves. Neohesperidin (126.8 mg/kg), followed by chlorogenic acid (99.96 mg/kg) and quercetin (43.44 and 21.44 mg/kg) were main phenolic compounds identified. Total phenols in powdered leaves' extract (635.6 mg GAE/L) was higher than in powdered seeds' extract (229.5 mg GAE/L). The activity against superoxide radical and hydroxyl radical was 92.4% and 73.1% by leaves' powder extract and 83.6% and 60.7% by crushed-leaf extract; seed-powder extract exhibited a pro-oxidation activity (-68.4%) against superoxide radical and the lowest antioxidant effect against the hydroxyl radical (55.0%).
ABSTRACT
Trypanosoma cruzi, the causative agent of Chagas disease (CD), contains exclusively Fe-dependent superoxide dismutases (Fe-SODs). During T. cruzi invasion to macrophages, superoxide radical (O2â¢-) is produced at the phagosomal compartment toward the internalized parasite via NOX-2 (gp91-phox) activation. In this work, T. cruzi cytosolic Fe-SODB overexpressers (pRIBOTEX-Fe-SODB) exhibited higher resistance to macrophage-dependent killing and enhanced intracellular proliferation compared with wild-type (WT) parasites. The higher infectivity of Fe-SODB overexpressers compared with WT parasites was lost in gp91-phox-/- macrophages, underscoring the role of O2â¢- in parasite killing. Herein, we studied the entrance of O2â¢- and its protonated form, perhydroxyl radical [(HO2â¢); pKa = 4.8], to T. cruzi at the phagosome compartment. At the acidic pH values of the phagosome lumen (pH 5.3 ± 0.1), high steady-state concentrations of O2â¢- and HO2⢠were estimated (â¼28 and 8 µM, respectively). Phagosomal acidification was crucial for O2â¢- permeation, because inhibition of the macrophage H+-ATPase proton pump significantly decreased O2â¢- detection in the internalized parasite. Importantly, O2â¢- detection, aconitase inactivation, and peroxynitrite generation were lower in Fe-SODB than in WT parasites exposed to external fluxes of O2â¢- or during macrophage infections. Other mechanisms of O2â¢- entrance participate at neutral pH values, because the anion channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid decreased O2â¢- detection. Finally, parasitemia and tissue parasite burden in mice were higher in Fe-SODB-overexpressing parasites, supporting the role of the cytosolic O2â¢--catabolizing enzyme as a virulence factor for CD.
Subject(s)
Cytosol/enzymology , Macrophages/metabolism , Superoxide Dismutase/metabolism , Superoxides/toxicity , Trypanosoma cruzi/enzymology , Animals , Chagas Disease/parasitology , Gene Expression Regulation, Enzymologic , Hydrogen-Ion Concentration , Mice , Mice, Inbred C57BL , Oxygen Consumption , Peroxynitrous Acid/metabolism , Phagosomes , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/pathogenicity , VirulenceABSTRACT
As condições de estresse biótico e abiótico impostas às plantas induzem a superprodução de espécies reativas de oxigênio (ROS), podendo causar danos às estruturas celulares e mesmo acarretar a morte da planta. As respostas bioquímicas e fisiológicas de plantas superiores ao estresse oxidativo incluem um eficiente sistema de defesa antioxidante, que envolve a atividade das enzimas superóxido dismutase, catalase, ascorbato peroxidase, peroxirredoxinas, dentre outras, além de metabólitos não enzimáticos, que, de forma conjunta, atuam na eliminação das ROS e na redução do dano oxidativo. Nesta revisão, serão abordados os principais sítios de produção de ROS e a ação de algumas enzimas do sistema de defesa antioxidante em plantas.(AU)
The biotic and abiotic stress conditions imposed on plants induces overproduction of reactive oxygen species (ROS), which can cause damage to cellular structures and even lead to the death of the plant. The biochemical and physiological responses of higher plants to oxidative stress includes an efficient antioxidant defense system, which involves the activity of the enzymes superoxide dismutase, catalase, ascorbate peroxidase, peroxiredoxines, among others, in addition to non-enzymatic metabolites, which, together, work on eliminating the ROS and in reducing oxidative damage. This review will address the main production sites of ROS and the action of some enzymes of antioxidative defense system in plants.(AU)
Subject(s)
Reactive Oxygen Species , Oxidative Stress , EnzymesABSTRACT
As condições de estresse biótico e abiótico impostas às plantas induzem a superprodução de espécies reativas de oxigênio (ROS), podendo causar danos às estruturas celulares e mesmo acarretar a morte da planta. As respostas bioquímicas e fisiológicas de plantas superiores ao estresse oxidativo incluem um eficiente sistema de defesa antioxidante, que envolve a atividade das enzimas superóxido dismutase, catalase, ascorbato peroxidase, peroxirredoxinas, dentre outras, além de metabólitos não enzimáticos, que, de forma conjunta, atuam na eliminação das ROS e na redução do dano oxidativo. Nesta revisão, serão abordados os principais sítios de produção de ROS e a ação de algumas enzimas do sistema de defesa antioxidante em plantas.
The biotic and abiotic stress conditions imposed on plants induces overproduction of reactive oxygen species (ROS), which can cause damage to cellular structures and even lead to the death of the plant. The biochemical and physiological responses of higher plants to oxidative stress includes an efficient antioxidant defense system, which involves the activity of the enzymes superoxide dismutase, catalase, ascorbate peroxidase, peroxiredoxines, among others, in addition to non-enzymatic metabolites, which, together, work on eliminating the ROS and in reducing oxidative damage. This review will address the main production sites of ROS and the action of some enzymes of antioxidative defense system in plants.
ABSTRACT
The biochemical responses of the enzymatic antioxidant system of a drought-tolerant cultivar (IACSP 94-2094) and a commercial cultivar in Brazil (IACSP 95-5000) grown under two levels of soil water restriction (70% and 30% Soil Available Water Content) were investigated. IACSP 94-2094 exhibited one additional active superoxide dismutase (Cu/Zn-SOD VI) isoenzyme in comparison to IACSP 95-5000, possibly contributing to the heightened response of IACSP 94-2094 to the induced stress. The total glutathione reductase (GR) activity increased substantially in IACSP 94-2094 under conditions of severe water stress; however, the appearance of a new GR isoenzyme and the disappearance of another isoenzyme were found not to be related to the stress response because the cultivars from both treatment groups (control and water restrictions) exhibited identical changes. Catalase (CAT) activity seems to have a more direct role in H2O2 detoxification under water stress condition and the shift in isoenzymes in the tolerant cultivar might have contributed to this response, which may be dependent upon the location where the excessive H2O2 is being produced under stress. The improved performance of IACSP 94-2094 under drought stress was associated with a more efficient antioxidant system response, particularly under conditions of mild stress.
Subject(s)
Antioxidants/metabolism , Genotype , Saccharum/physiology , Stress, Physiological , Water , Catalase/metabolism , Glutathione Reductase/metabolism , Hydrogen Peroxide/metabolism , Lipid Peroxidation , Saccharum/enzymology , Saccharum/genetics , Saccharum/metabolismABSTRACT
BACKGROUND: Peroxynitrite, the product of the reaction between superoxide radicals and nitric oxide, is an elusive oxidant with a short half-life and a low steady-state concentration in biological systems; it promotes nitroxidative damage. SCOPE OF REVIEW: We will consider kinetic and mechanistic aspects that allow rationalizing the biological fate of peroxynitrite from data obtained by a combination of methods that include fast kinetic techniques, electron paramagnetic resonance and kinetic simulations. In addition, we provide a quantitative analysis of peroxynitrite production rates and conceivable steady-state levels in living systems. MAJOR CONCLUSIONS: The preferential reactions of peroxynitrite in vivo include those with carbon dioxide, thiols and metalloproteins; its homolysis represents only <1% of its fate. To note, carbon dioxide accounts for a significant fraction of peroxynitrite consumption leading to the formation of strong one-electron oxidants, carbonate radicals and nitrogen dioxide. On the other hand, peroxynitrite is rapidly reduced by peroxiredoxins, which represent efficient thiol-based peroxynitrite detoxification systems. Glutathione, present at mM concentration in cells and frequently considered a direct scavenger of peroxynitrite, does not react sufficiently fast with it in vivo; glutathione mainly inhibits peroxynitrite-dependent processes by reactions with secondary radicals. The detection of protein 3-nitrotyrosine, a molecular footprint, can demonstrate peroxynitrite formation in vivo. Basal peroxynitrite formation rates in cells can be estimated in the order of 0.1 to 0.5µMs(-1) and its steady-state concentration at ~1nM. GENERAL SIGNIFICANCE: The analysis provides a handle to predict the preferential fate and steady-state levels of peroxynitrite in living systems. This is useful to understand pathophysiological aspects and pharmacological prospects connected to peroxynitrite. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
Subject(s)
Electron Spin Resonance Spectroscopy/methods , Peroxynitrous Acid/analysis , Peroxynitrous Acid/metabolism , Animals , Humans , KineticsABSTRACT
Identification of metabolic targets of environmental stress factors is critical to improve the stress tolerance of plants. Studying the biochemical and physiological responses of plants with different capacities to deal with stress is a valid approach to reach this objective. Lotus corniculatus (lotus) and Trifolium pratense (clover) are legumes with contrasting summer stress tolerances. In stress conditions, which are defined as drought, heat or a combination of both, we found that differential biochemical responses of leaves explain these behaviours. Lotus and clover showed differences in water loss control, proline accumulation and antioxidant enzymatic capacity. Drought and/or heat stress induced a large accumulation of proline in the tolerant species (lotus), whereas heat stress did not cause proline accumulation in the sensitive species (clover). In lotus, Mn-SOD and Fe-SOD were induced by drought, but in clover, the SOD-isoform profile was not affected by stress. Moreover, lotus has more SOD-isoforms and a higher total SOD activity than clover. The functionality and electrophoretic profile of photosystem II (PSII) proteins under stress also exhibited differences between the two species. In lotus, PSII activity was drastically affected by combined stress and, interestingly, was correlated with D2 protein degradation. Possible implications of this event as an adaption mechanism in tolerant species are discussed. We conclude that the stress-tolerant capability of lotus is related to its ability to respond to oxidative damage and adaption of the photosynthetic machinery. This reveals that these two aspects should be included in the evaluation of the tolerance of species to stress conditions.
Subject(s)
Adaptation, Physiological , Droughts , Hot Temperature , Lotus/physiology , Oxidoreductases/metabolism , Photosystem II Protein Complex/metabolism , Trifolium/physiology , Antioxidants , Lotus/enzymology , Lotus/metabolism , Plant Proteins/metabolism , Proline/metabolism , Stress, Physiological , Superoxide Dismutase/metabolism , Trifolium/enzymology , Trifolium/metabolism , WaterABSTRACT
We studied the bis-allylic proton transfer reaction from 1,4-pentadiene to superoxide radical anion (O2.-). Minima and transition state geometries, as well as thermochemical parameters were computed at the B3LYP/6-311+G(3df,2p) level of theory. The electronic wave functions of reactants, intermediates, and products were analyzed within the framework of the Quantum Theory of Atoms in Molecules. The results show the formation of strongly hydrogen bonded complexes between the 1,4-pentadien- 3-yl anion and the hydroperoxyl radical as the reaction products. These product complexes (PCs) are more stable than the isolated reactants and much more stable than the isolated products. This reaction occurs via pre-reactive complexes which are more stable than the PCs and the transition states. This is in agreement with the fact that the net proton transfer reaction that leads to free products is an endothermic and nonspontaneous process.
Nosotros estudiamos la reacción de transferencia de protón bis-alílico del 1,4-pentadieno al radical anión superóxido (O2.--). Las geometrías de los mínimos y de los estados de transición, así como también los parámetros termoquímicos se calcularon usando el nivel de teoría B3LYP/6-311+G(3df,2p). Las funciones de onda electrónicas de los reactantes, intermedios y productos se analizaron dentro del marco de la teoría cuántica de átomos en moléculas. Nuestros resultados muestran la formación de complejos estabilizados por enlaces de hidrógeno entre el anión 1,4pentadien-3-ilo y el radical hidroperoxilo como productos de reacción. Estos complejos producto (PCs) son más estables que los reactantes aislados y mucho más estables que los productos aislados. Esta reacción ocurre vía la formación de complejos pre-reactivos, los cuales son más estables que los PCs y los estados de transición. Estos resultados están de acuerdo con el hecho de que la reacción global de transferencia de protón que conduce a la formación de los productos libres es un proceso endotérmico y no espontáneo.
Estudou-se a reação de transferência do próton bis-alílico do 1,4-pentadieno ao radical ânion superóxido (O2.-). As geometrias dos mínimos e dos estados de transição, bem como os parâmetros termoquímicos foram calculadas utilizando o nível de teoria B3LYP/6-311+G(3df, 2p). As funçÃμes de onda eletrònica dos reagentes, intermediários e produtos foram analisadas no âmbito da teoria quântica de átomos em moléculas. Os resultados obtidos demonstram a formação de complexos estabilizados por ligaçÃμes de hidrogênio entre o ânion 1,4-pentadieno- 3-ilo e o radical hidroperoxilo como produtos de reação. Estes complexos formados como produtos (PCs) são mais estáveis do que os reagentes isolados e muito mais estáveis do que os produtos isolados. Esta reação ocorre por meio de complexos pré-reativos mais estáveis do que os PCs e os estados de transição. Estes resultados estão de acordo com o fato da reação global de transferência de próton que conduz à formação dos produtos livres, é um processo endotérmico e não espontâneo.
ABSTRACT
Objetivo: Avaliar a liberação espontânea de ânion superóxidopor granulócitos de sangue periférico de pacientescomasma crônica não-controlada antes e após corticoterapia e de indivíduos sadios. Métodos: Foram estudados 32 pacientes entre 6 e 18 anos (média 12,04 anos) e 29 indivíduos sadios como grupo decomparação.Os pacientes oramagrupados de acordocomo volumeexpiratório forçado no primeiro segundo: grupo I, volume expiratórioforçado no primeiro segundo entre 60 e 80%, 19 pacientes; e grupo II, volume expiratório forçado no primeiro segundo = 60%, 13 pacientes. A liberação espontânea de superóxido por granulócitos, medida por espectrofotometria utilizando superóxido dismutase, foi avaliada nos pacientes antes e após o tratamento com prednisona por via oral e beclometasona, budesonida ou fluticasona administradas por via inalatória. Na análise estatística foramutilizados os testes de análise de variância, Tukey e de Wilcoxon.Resultados: Comparando-se a liberação de ânion superóxido por granulócitos dos pacientes asmáticos e indivíduos sadios observamosque a liberação foi maior nos asmáticos não-controladosdo grupo II (p < 0,05). Avaliando-se a liberação de superóxido pelas células dos pacientes antes e após a terapiacomcorticosteroideuma diminuição significativa foi observada apenas no grupo I. Conclusão: O impacto dos glicocorticoides sobre a modulação da inflamação ocorreu nos indivíduos asmáticos não-controlados com volume expiratório forçado no primeiro segundo entre 60 e 80%.Naqueles com volume expiratório forçado no primeiro segundo = 60não foi observada essa modulação, havendo necessidade de mais estudos para avaliar o impacto de tal achado nos pacientes asmáticos.
Objective: To evaluate spontaneous release of superoxide anion by peripheral blood granulocytes of atopic patients with uncontrolled asthma undergoing glucocorticoid therapy and of healthy subjects. Methods: We studied 32 patients, aged 6 to 18 (mean 12.04), and 29 healthy subjects as a comparative group. Patients weregrouped according to the forced expiratory vital capacity in the firstsecond. Group I, forced expiratory vital capacity in the first second of between60and80%,had 19 patients, and group II, forced expiratoryvital capacity in the first second=60%,had 13 patients. Spontaneous superoxide release by granulocytes was measured by aspectrophotometer method based on superoxide dismutase, before and after oral prednisone and beclomethasone, budesonide or fluticasone inhaled therapy. Statistical analyses were performed using ANOVA, Wilcoxon and Tukey tests. Results: Comparing the superoxide anion release bygranulocytes of asthmatic patients and healthy subjects,weobserved a higher release by cells of the uncontrolled patient group II (p < 0.05). Evaluating the superoxide release by cells of asthmatic patients before and after steroid therapy, a significant decrease was found only in patient group I.Conclusion: The impact of corticosteroids on inflammatorymodulation occurred in the uncontrolled asthmatics with forced expiratory vital capacity in the first second between 60 and 80%. In those with forced expiratory vital capacity in the first second of = 60%, this findingwas not observed. Further studies are necessary to evaluate the effect of this finding on asthmatic patients.