RESUMEN
The respiratory tract, from the nose to the lung, behaves as an anatomical and pathophysiological unit under a holistic model. Lower airway abnormalities, such as bronchial hyperresponsiveness, reduced lung function and inflammation of the bronchial mucosa without clinical expression, have been observed in patients with rhinitis without asthma. These would be the consequence of a common systemic inflammatory phenomenon with simultaneous impact on the nose and lung. For unknown reasons, these patients do not exhibit a full clinical expression, which could mean an increased risk of developing asthma. In this review we address the frequency and characteristics of existing pulmonary abnormalities in children and adolescents with chronic rhinitis that derive from our previous research and, more recently, within the project "Allergic Respiratory Disease: The United Airway Concept" supported by the Universidad Católica de Córdoba, and a comparative analysis with the evidence provided by other authors in the medical literature.
El aparato respiratorio, desde la nariz al pulmón, se comporta como una unidad anatómica y fisiopatológica bajo un modelo holístico. Se han observado alteraciones pulmonares sin traducción clínica en pacientes con rinitis sin asma, que se manifiestan como hiperreactividad bronquial, reducción de la función pulmonar e inflamación bronquial. Estas serían consecuencia de un fenómeno inflamatorio sistémico con impacto simultáneo en nariz y pulmón, que por razones desconocidas no tiene una expresión clínica completa, pero que podrían significar un mayor riesgo de desarrollo de asma. En esta revisión abordamos la frecuencia y características de las anormalidades pulmonares existentes en niños y adolescentes con rinitis crónica derivadas de nuestras investigaciones previas y, más recientemente, del proyecto "Enfermedad Alérgica Respiratoria: El Concepto de Unidad de la Vía Aérea", línea de investigación acreditada por la Universidad Católica de Córdoba y un análisis comparativo con las evidencias aportadas por otros autores en la literatura médica.
Asunto(s)
Rinitis , Humanos , Niño , Adolescente , Rinitis/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Hiperreactividad Bronquial/etiología , Asma/fisiopatología , Enfermedad CrónicaRESUMEN
Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B2 antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.
Asunto(s)
Bradiquinina , Líquido del Lavado Bronquioalveolar , Capsaicina , Captopril , Canales Catiónicos TRPV , Animales , Captopril/farmacología , Canales Catiónicos TRPV/metabolismo , Ratas , Masculino , Bradiquinina/farmacología , Capsaicina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Ratas Sprague-Dawley , Resistencia de las Vías Respiratorias/efectos de los fármacos , Antagonistas del Receptor de Bradiquinina B2/farmacología , Relación Dosis-Respuesta a Droga , Hiperreactividad Bronquial/inducido químicamente , Hiperreactividad Bronquial/tratamiento farmacológico , Neuronas/efectos de los fármacos , Neuronas/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Stachytarpheta cayennensis (Verbenaceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory diseases. AIMS OF THE STUDY: To investigate the effects of different doses of standardized hydro-ethanolic (SCH) and aqueous (SCA) extracts of aerial parts of S. cayennensis using a murine ovalbumin (OVA)-induced asthma model. MATERIALS AND METHODS: The major constituents of the plant extracts were identified and standardized by ultra-performance liquid chromatography coupled with mass spectrometry. Balb/c mice were challenged with OVA solution and treated concomitantly by intraperitoneal injection of standardized SCH or SCA extracts at 50, 100, and 200 mg/kg concentrations. OVA-challenged control animals were treated with either dexamethasone (OVA-DEX) or saline solution (OVA-SAL). After challenge, we assessed in vivo bronchial hyperresponsiveness, airway inflammation (number of cells), peribronchial inflammation (histological analysis) and production of OVA-specific IgE and interleukin (IL)-4, IL-5, and IL-13 (ELISA). RESULTS: Acteoside, isoacteoside, and ipolamiide were the major constituents of SCH and SCA. The respective concentrations of acteoside in SCH and SCA were 78 and 98 µg/mL, while those of ipolamiide were 30 and 19 µg/mL. Treatment with 200 mg/kg of SCH or SCA decreased IL-4, IL-5, and IL-13 in lung homogenates. These reductions were accompanied by a lower influx of inflammatory cells (eosinophils, lymphocytes, and macrophages) to the airways and lungs. In addition to the anti-inflammatory effects, administration of SCA, but not SCH, ameliorated the parameters of bronchial hyperresponsiveness and decreased levels of circulating OVA-specific IgE. CONCLUSION: The results presented herein demonstrate for the first time the anti-asthmatic activity of S. cayennensis extracts in a murine model, thereby supporting the ethnopharmacological uses of the plant.
Asunto(s)
Antiasmáticos , Hiperreactividad Bronquial , Verbenaceae , Ratones , Animales , Antiasmáticos/efectos adversos , Interleucina-13 , Modelos Animales de Enfermedad , Interleucina-5 , Líquido del Lavado Bronquioalveolar , Hiperreactividad Bronquial/tratamiento farmacológico , Ovalbúmina/farmacología , Ratones Endogámicos BALB C , Pulmón , Inmunoglobulina E , Inflamación/tratamiento farmacológico , Citocinas/farmacologíaRESUMEN
OBJECTIVE: To evaluate the effect of a hydroethanolic extract of Momordica charantia L. ("bitter melon", Cucurbitaceae) leaves (MCHA) on ovalbumin (OVA)-induced asthma model. Balb/c mice were sensitized twice and challenged for 4 alternate days with OVA and then treated with MCHA (500 mg/kg) for 7 consecutive days. METHODS: Control groups received treatment with normal saline or dexamethasone (2 mg/kg) on the same day. We assessed in vivo bronchial hyperresponsiveness and ex-vivo inflammation and mucus production in bronchoalveolar lavage (BAL), lung homogenates, and lung tissue. RESULTS: MCHA significantly improved airway hyperresponsiveness near baseline levels. MCHA administration significantly improved airway and lung inflammation, demonstrated by decreased total and inflammatory cells in BAL, lower levels of IL-5 and IL-13 in lung homogenate, and fewer inflammatory cells in lung tissue. Additionally, MCHA significantly diminished goblet cells in lung tissue. CONCLUSIONS: Administration of a hydroethanolic extract of M. charantia leaves was effective in treating OVA-induced asthma in an animal model.
Asunto(s)
Asma , Hiperreactividad Bronquial , Momordica charantia , Animales , Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar , Citocinas , Modelos Animales de Enfermedad , Humanos , Inflamación/tratamiento farmacológico , Pulmón , Ratones , Ratones Endogámicos BALB C , OvalbúminaRESUMEN
Objective:Pyrostegia venusta (Ker-Gawl.) Miers (Bignoniaceae) is a perennial invasive vine, distributed worldwide. In folk medicine, its parts are used for the treatment of inflammatory respiratory diseases. Extracts of P. venusta have antioxidant, antimicrobial, and antinociceptive properties. The aim of this study was to evaluate the effects of two extracts (aqueous and hydroethanolic) of P. venusta in the treatment of asthma in an animal model.Methods: Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally (ip), one week apart, and after one week, challenged with OVA intranasally on four alternate days. Mice were treated ip with 300 mg/kg of aqueous or hydroethanolic extracts for seven consecutive days. Control groups received saline on the same days. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, lung and airway inflammation, and antioxidant activity in lung tissue were assessed.Results: Treatment with aqueous extract significantly decreased bronchial hyperresponsiveness, measured by total and tissue resistance and elastance. The administration of hydroethanolic extract did not reduce bronchial hyperresponsiveness. In addition, both extracts significantly reduced total cell and eosinophil counts in bronchoalveolar lavage. Both extracts did not change significantly IL-4, IL-5, IL-9, IL-13, IFN-gamma, and TGF-beta levels. Of note, only the aqueous extract significantly increased the total antioxidant activity and reduced lung inflammation.Conclusion: Aqueous extract of P. venusta reduced bronchial hyperresponsiveness, lung and airway inflammation, probably via an antioxidant mechanism. These results demonstrate that P. venusta may have potential for asthma treatment.
Asunto(s)
Antioxidantes/farmacología , Asma/tratamiento farmacológico , Bignoniaceae , Extractos Vegetales/farmacología , Animales , Hiperreactividad Bronquial/tratamiento farmacológico , Modelos Animales de Enfermedad , Etanol , Mediadores de Inflamación/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Células TH1/metabolismo , Células Th2/metabolismo , AguaRESUMEN
INTRODUCTION: Asthma is a major cause of morbidity and mortality in children worldwide, but many cases may remain undiagnosed. Community health worker (CHW) programs have improved detection of other diseases such as childhood pneumonia, but none have been validated for detection of asthma in resource-poor settings. We hypothesized that a CHW administered questionnaire would be effective in case-detection of asthma in a poor Nicaraguan community. METHODS: We enrolled children aged 2-17 from a small semiurban Nicaraguan community. A trained CHW administered a questionnaire based on a previously validated school-based screening questionnaire, which was compared to pediatric pulmonologist evaluation as a reference standard. We determined the questionnaire's sensitivity, specificity, and positive and negative likelihood ratios at different score cut-points. RESULTS: A total of 199 out of 218 eligible children were enrolled. Total asthma prevalence based on physician diagnosis was 33%. Mean scores on the CHW questionnaire were 3.6 points out of 22 (SD = 4.3) for nonasthmatics and 11.0 points (SD = 5.3) for children with asthma (p < .001). Area under the curve was 0.87. Multivariable analysis showed increased association of asthma/reactive airways disease with respiratory infection in the first 3 months of life and with family history of asthma. CONCLUSIONS: Prevalence of asthma in this community was high compared to previously reported national prevalence (15.2%), possibly due to increased exposure to risk factors. The questionnaire had a high area under the receiver operating characteristic curve, making it an excellent screening tool. This questionnaire could greatly increase the detection of asthma, allowing for education and referral for ongoing care.
Asunto(s)
Asma , Hiperreactividad Bronquial , Asma/diagnóstico , Asma/epidemiología , Agentes Comunitarios de Salud , Humanos , Nicaragua/epidemiología , Encuestas y CuestionariosRESUMEN
Hydrogen chloride is available commercially as an anhydrous gas or an aqueous solution, hydrochloric acid. Exposure to this gas has been associated with the development of reactive airways dysfunction syndrome. However, there are few published reports. A 37-year-old woman developed progressive bronchospasm and acute respiratory failure after cleaning an enclosed space with an unknown concentration of hydrochloric acid gas from a cleaning substance. She had no prior history of asthma or atopy. Severe bronchospasm developed, leading to hypoxemia and diffuse interstitial infiltrates, necessitating orotracheal intubation and admission to the intensive care unit. Asthma-like symptoms such as cough, wheezing, and dyspnea; requiring bronchodilators, and repeated hospitalizations are persistent a year after the accident. Pulmonary function testing showed mild airflow obstruction.
Asunto(s)
Humanos , Femenino , Adulto , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Insuficiencia Respiratoria/etiología , Ácido Clorhídrico/efectos adversos , Inhalación , Hiperreactividad Bronquial/complicacionesRESUMEN
Introduction: Reports have shown that the onset of diabetes mellitus (DM) in patients previously diagnosed with asthma decreases asthmatic symptoms, whereas insulin aggravates asthma. The present study evaluated the modulatory effect of insulin on the development of allergic airway inflammation in diabetic mice. Materials and Methods: To evaluate the effects of relative insulin deficiency, an experimental model of diabetes was induced by a single dose of alloxan (50 mg/kg, i.v.). After 10 days, the mice were sensitized with ovalbumin [OVA, 20 µg and 2 mg of Al(OH)3, i.p.]. A booster immunization was performed 6 days after the first sensitization [20 µg of OVA and 2 mg of Al(OH)3, i.p.]. The OVA challenge (1 mg/mL) was performed by daily nebulization for 7 days. Diabetic animals were treated with multiple doses of neutral protamine Hagedorn (NPH) before each challenge with OVA. The following parameters were measured 24 h after the last challenge: (a) the levels of p38 MAP kinase, ERK 1/2 MAP kinases, JNK, STAT 3, and STAT 6 in lung homogenates; (b) the serum profiles of immunoglobulins IgE and IgG1; (c) the concentrations of cytokines (IL-4, IL-5, IL-10, IL-13, TNF-α, VEGF, TGF-ß, and IFN-γ) in lung homogenates; (d) cells recovered from the bronchoalveolar lavage fluid (BALF); (e) the profiles of immune cells in the bone marrow, lung, thymus, and spleen; and (f) pulmonary mechanics using invasive (FlexiVent) and non-invasive (BUXCO) methods. Results: Compared to non-diabetic OVA-challenged mice, OVA-challenged diabetic animals showed decreases in ERK 1 (2-fold), ERK 2 (7-fold), JNK (phosphor-54) (3-fold), JNK/SAPK (9-fold), STAT3 (4-fold), the levels of immunoglobulins, including IgE (1-fold) and IgG1 (3-fold), cytokines, including Th2 profile cytokines such as IL-4 (2-fold), IL-5 (2-fold), IL-13 (4-fold), TNF-α (2-fold), VEGF (2-fold), and TGF-ß (2-fold), inflammatory infiltrates (14-fold), T cells, NK cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. STAT6 was absent, and no eosinophilia was observed in BALF. Insulin treatment restored all parameters. Conclusion: The data suggested that insulin modulates immune cell phenotypes and bronchial hyperresponsiveness in the development of allergic airway inflammation in diabetic mice.
Asunto(s)
Asma/inmunología , Hiperreactividad Bronquial/inmunología , Diabetes Mellitus Experimental/tratamiento farmacológico , Eosinófilos/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Insulina Isófana/administración & dosificación , Linfocitos/efectos de los fármacos , Fenotipo , Aloxano/efectos adversos , Animales , Asma/inducido químicamente , Hiperreactividad Bronquial/inducido químicamente , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/inmunología , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Pulmón/inmunología , Pulmón/metabolismo , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversos , Organismos Libres de Patógenos EspecíficosRESUMEN
Asthma is a chronic inflammatory disease of the airways characterized by immune cell infiltrates, bronchial hyperresponsiveness, and declining lung function. Thus, the possible effects of virgin coconut oil on a chronic allergic lung inflammation model were evaluated. Morphology of lung and airway tissue exhibited peribronchial inflammatory infiltrate, epithelial hyperplasia, and smooth muscle thickening in guinea pigs submitted to ovalbumin sensitization, which were prevented by virgin coconut oil supplementation. Additionally, in animals with lung inflammation, trachea contracted in response to ovalbumin administration, showed a greater contractile response to carbachol (CCh) and histamine, and these responses were prevented by the virgin coconut oil supplementation. Apocynin, a NADPH oxidase inhibitor, did not reduce the potency of CCh, whereas tempol, a superoxide dismutase mimetic, reduced potency only in nonsensitized animals. Catalase reduced the CCh potency in nonsensitized animals and animals sensitized and treated with coconut oil, indicating the participation of superoxide anion and hydrogen peroxide in the hypercontractility, which was prevented by virgin coconut oil. In the presence of L-NAME, a nitric oxide synthase (NOS) inhibitor, the CCh curve remained unchanged in nonsensitized animals but had increased efficacy and potency in sensitized animals, indicating an inhibition of endothelial NOS but ineffective in inhibiting inducible NOS. In animals sensitized and treated with coconut oil, the CCh curve was not altered, indicating a reduction in the release of NO by inducible NOS. These data were confirmed by peribronchiolar expression analysis of iNOS. The antioxidant capacity was reduced in the lungs of animals with chronic allergic lung inflammation, which was reversed by the coconut oil, and confirmed by analysis of peribronchiolar 8-iso-PGF2α content. Therefore, the virgin coconut oil supplementation reverses peribronchial inflammatory infiltrate, epithelial hyperplasia, smooth muscle thickening, and hypercontractility through oxidative stress and its interactions with the NO pathway.
Asunto(s)
Antioxidantes/uso terapéutico , Hiperreactividad Bronquial/terapia , Aceite de Coco/uso terapéutico , Neumonía/terapia , Animales , Antioxidantes/farmacología , Enfermedad Crónica , Aceite de Coco/farmacología , Femenino , Cobayas , MasculinoRESUMEN
The bronchial challenge test with exercise aims to demonstrate the presence of exercise-induced bronchial hyperreactivity, characteristic of bronchial asthma. Its realization is well standardized, requiring special environmental conditions, preparation and submaximum effort of the patient. The response is measured by spirometry, and it is considered a positive exercise test a drop in the expired volume at the first second (FEV1) of 10%. This article describes the elements necessary to facilitate this exam, according to national and international standards and guidelines.
La prueba de provocación bronquial con ejercicio tiene como objetivo demostrar la presencia de hiperreactividad bronquial inducida por ejercicio, característica del asma bronquial. Su realización está bien estandarizada, requiriendo de condiciones ambientales especiales, preparación y esfuerzo submáximo del paciente. La respuesta se mide mediante espirometría, y se considera una prueba de provocación con ejercicio positivo, a una caída del volumen espirado al primer segundo (VEF1) del 10%. En este artículo se describen los elementos necesarios para facilitar la realización de este examen, acorde a normas y guías nacionales e internacionales.
Asunto(s)
Humanos , Niño , Pruebas de Provocación Bronquial/métodos , Ejercicio Físico/fisiología , Hiperreactividad Bronquial/diagnóstico , Índice de Severidad de la Enfermedad , Volumen Espiratorio Forzado/fisiología , Hiperreactividad Bronquial/fisiopatologíaRESUMEN
This document updates the recommendations of the bronchial challenge test with methacholine in children. It is based primarily on the recommendations contained in the guide on the technical standard of the bronchial challenge test for methacholine from the European Society of Respiratory Diseases. The main change is the recommendation to use PD20 (methacholine dose that causes a 20% drop in FEV1) instead of PC20 (methacholine concentration that causes a 20% drop in FEV1), which allows for comparable results when different devices and different protocols are used.
Este documento actualiza las recomendaciones de la prueba de provocación bronquial con metacolina en niños. Se basa fundamentalmente en las recomendaciones contenidas en la guía sobre el estándar técnico de la prueba de provocación bronquial de metacolina de la Sociedad Europea de Enfermedades Respiratorias. El principal cambio es la recomendación de utilizar la PD20 (dosis de metacolina que provoca una caída de 20% del VEF1) en vez de PC20 (concentración de metacolina que provoca una caída del 20% en el VEF1), lo cual permite tener resultados comparables cuando se usan diferentes dispositivos y diferentes protocolos.
Asunto(s)
Humanos , Niño , Pruebas de Provocación Bronquial/métodos , Cloruro de Metacolina/administración & dosificación , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/fisiopatologíaRESUMEN
Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function. In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity. In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression. In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit. This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma/fisiopatología , Matriz Extracelular/patología , Pulmón/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Animales , Hiperreactividad Bronquial/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo II/metabolismo , Modelos Animales de Enfermedad , Fibronectinas/metabolismo , HumanosRESUMEN
Glucagon has been shown to be beneficial as a treatment for bronchospasm in asthmatics. Here, we investigate if glucagon would prevent airway hyperreactivity (AHR), lung inflammation, and remodeling in a murine model of asthma. Glucagon (10 and 100 µg/Kg, i.n.) significantly prevented AHR and eosinophilia in BAL and peribronchiolar region induced by ovalbumin (OVA) challenge, while only the dose of 100 µg/Kg of glucagon inhibited subepithelial fibrosis and T lymphocytes accumulation in BAL and lung. The inhibitory action of glucagon occurred in parallel with reduction of OVA-induced generation of IL-4, IL-5, IL-13, TNF-α, eotaxin-1/CCL11, and eotaxin-2/CCL24 but not MDC/CCL22 and TARC/CCL17. The inhibitory effect of glucagon (100 µg/Kg, i.n.) on OVA-induced AHR and collagen deposition was reversed by pre-treatment with indomethacin (10 mg/Kg, i.p.). Glucagon increased intracellular cAMP levels and inhibits anti-CD3 plus anti-CD28-induced proliferation and production of IL-2, IL-4, IL-10, and TNF- α from TCD4+ cells in vitro. These findings suggest that glucagon reduces crucial features of asthma, including AHR, lung inflammation, and remodeling, in a mechanism probably associated with inhibition of eosinophils accumulation and TCD4+ cell proliferation and function. Glucagon should be further investigated as an option for asthma therapy.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Hiperreactividad Bronquial/prevención & control , Glucagón/farmacología , Ovalbúmina/farmacología , Neumonía/prevención & control , Animales , Asma/prevención & control , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular/efectos de los fármacos , Quimiocina CCL24/metabolismo , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones Endogámicos , Receptores de Glucagón/metabolismoRESUMEN
RESUMEN Introducción: El sistema nervioso autónomo desempeña un papel importante en los reajustes cardiovasculares al ejercicio. En la hiperreactividad cardiovascular existe una mayor sensibilidad del sistema simpático ante diferentes estímulos estresantes. Objetivo: Determinar las características del control autonómico cardíaco en adultos jóvenes con diferentes grados de reactividad cardiovascular en condiciones basales y durante el ejercicio isométrico. Método: La muestra estuvo constituida por 97 individuos de ambos sexos, y se dividió en tres grupos: normorreactivos, hiperreactivos y con respuesta hipertensiva, de acuerdo a la respuesta presora a la prueba del peso sostenido. A todos los individuos se les realizó un estudio de variabilidad de la frecuencia cardíaca en reposo y durante la prueba isométrica. Se estudiaron las variables en el dominio de la frecuencia: baja, alta, relación baja/alta en reposo, y los parámetros del diagrama de Poincaré en reposo y durante el ejercicio (valores de desviación estándar 1 [SD1], 2 [SD2], y la razón entre ambos). Resultados: En estado basal los individuos hiperreactivos y con respuesta hipertensiva presentaron un predominio simpático sobre la función cardíaca y una menor variabilidad de la frecuencia cardíaca. Durante el ejercicio isométrico disminuyeron los valores de los ejes SD1 y SD2 en todos los grupos y la razón SD1/SD2 decreció en individuos normorreactivos y con respuesta hipertensiva; pero apenas se modificó en los hiperreactivos. Conclusiones: En los individuos con hiperreactividad cardiovascular ya está presente un desbalance autonómico en estado basal y existe una reducción de la modulación autonómica vagal durante el ejercicio, que puede favorecer el desarrollo de la hipertensión arterial.
ABSTRACT Introduction: The autonomic nervous system plays an important role in cardiovascular readjustments to exercise. In cardiovascular hyperreactivity there is a greater sensitivity of the sympathetic system to different stressors. Objective: To determine the characteristics of cardiac autonomic control in young adults with different degrees of cardiovascular reactivity under basal conditions and during isometric exercise. Method: The sample consisted of 97 individuals of both sexes, and was divided into three groups: normoreactive, hyperreactive and with hypertensive response, according to the pressor response to weight-bearing tests. The individuals underwent a complete study of heart rate variability at rest and during isometric test. The frequency domain for the variables was: low, high, low/high resting ratio, and the parameters of Poincaré plots at rest and during exercise (values of standard deviation 1 [SD1], 2 [SD2], and the reason between them). Results: Under basal conditions, hyperreactive individuals with a hypertensive response had a sympathetic predominance over cardiac function and lower heart rate variability. During the isometric exercise SD1 and SD2 axes values decreased in all groups and SD1/SD2 ratio decreased in normoreactive individuals with hypertensive response; but it was hardly modified in those hyper-reactive. Conclusions: Individuals with cardiovascular hyperreactivity have a prior autonomic imbalance under basal conditions and a reduction of autonomic vagal modulation during exercise that may favor the development of arterial hypertension.
Asunto(s)
Hiperreactividad Bronquial , Ejercicio Físico , Frecuencia Cardíaca , Contracción IsométricaRESUMEN
Dados mostram que o aparecimento do diabetes mellitus (DM), em pacientes previamente asmáticos, diminui os sintomas da asma, enquanto a insulina agrava a asma. Devido a dados na literatura e por dados prévios do nosso grupo, o presente estudo teve como objetivo avaliar o efeito modulatório da insulina na inflamação alérgica pulmonar em camundongos diabéticos e saudáveis. Camundongos machos dibéticos BALB/c (aloxana, 50mg/kg, iv, 10 dias) foram sensibilizados com ovalbumina (OVA, 20 µg e Al (OH)3, 2 mg) 10 dias após a injeção de aloxana e uma dose reforço foi dada, após 12 dias da primeira de sensibilização, após 6 dias da dose reforço, os animais foram expostos a nebulização durante 7 dias com solução de OVA (1mg/mL) ou solução salina (SAL). Animais diabéticos foram tratados com doses múltiplas de Protamine Hagedorn Neutro (NPH) 2UI e 1UI, respectivamente, por via subcutânea 12 horas antes do desafio com OVA (às 19h) e 1UI (às 7h) 2h antes de cada desafio com OVA. Os animais não diabéticos receberam 1UI de insulina, pela mesma via 2h antes de cada desafio (às 7h), 24h após o último desafio, realizaram-se as seguintes análises: a) expressão de proteína quinase p38, proteína quinase regulada por sinais extracelulares 1 e 2 (ERK 1/2), proteína quinase ativada por estresse ou c-jun NH2- terminal (JNK) , transdutor de sinal e ativador de transcrição 3 (STAT 3) e transdutor de sinal e ativador de transcrição 6 (pSTAT 6) no homogenato de pulmão; b) perfil de imunoglobulinas presentes no soro; c) concentrações de interleucina (IL) IL-4, IL-5, IL-10, IL-13, fator de necrose tumoral alfa (TNF-α), fator de crescimento endotelial vascular (VEGF), fator de crescimento transformador beta (TGF-ß) e interferon-gamma IFN-γ em homogenato de pulmão; d) migração celular em fluído do lavado broncoalveolar (LBA); e) perfil de células imunes na medula óssea, pulmão, timo e baço; f) mecânica pulmonar por BUXCO e FlexiVent. Em comparação com camundongos não diabéticos desafiados com OVA, os animais diabéticos desafiados com OVA mostraram diminuição em: ERK 1, ERK 2, JNK (fosfo54), JNK / SAPK, STAT3, pSTAT6 estava ausente; concentração da imunoglobulinas IgE, IgG1; perfil de citocinas Th2 como IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-ß; infiltrado inflamatório e) ausência de eosinofilia no LBA; células T, células B e eosinófilos na medula óssea, pulmão, timo e baço, e hiper-reatividade das vias aéreas. O tratamento com insulina restaubeleceu todos os parâmetros estudados. Portanto, sugerem que a insulina modula a inflamação alérgica pulmonar tardia em camundongos diabéticos
Data show that the onset of diabetes mellitus (DM) in previously asthmatic patients decreases asthma symptoms while insulin worsens asthma. Due to data in the literature and previous data from our group, the present study aimed to evaluate the modulatory effect of insulin on pulmonary allergic inflammation in diabetic and healthy mice. Ovalbumin (OVA, 20 µg and Al (OH)3, 2 mg) were sensitized at 10 days after alloxan injection and a booster dose was given , after 12 days of the first sensitization, after 6 days of booster dose, the animals were exposed to nebulization for 7 days with OVA solution (1mg / mL) or saline solution (SAL). Diabetic animals were treated with multiple doses of Protamine Hagedorn Neutral (NPH) 2UI and 1UI, respectively, subcutaneously 12 hours prior to challenge with OVA (at 7pm) and 1UI (at 7h) 2h before each challenge with OVA. Non-diabetic animals received 1UI of insulin, via the same route 2h before each challenge (at 7h), 24h after the last challenge, the following analyzes were performed: a) expression of protein kinase p38, protein kinase regulated by extracellular signals 1 and 2 (ERK 1/2), stress-activated or c-jun NH2-terminal protein kinase (JNK), signal transducer and transcriptional activator 3 (STAT 3) and signal transducer and transcriptional activator 6 (pSTAT 6) in the lung homogenate; b) profile of immunoglobulins present in serum; c) concentrations of interleukin (IL) IL-4, IL-5, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), transforming TGF-ß) and interferon-gamma IFN-γ in lung homogenate; d) cell migration in bronchoalveolar lavage fluid (BAL); e) profile of immune cells in the bone marrow, lung, thymus and spleen; f) Pulmonary mechanics by BUXCO and FlexiVent. In contrast to non-diabetic mice challenged with OVA, diabetic animals challenged with OVA showed decrease in: ERK 1, ERK 2, JNK (phospho54), JNK / SAPK, STAT3, pSTAT6 was absent; IgE immunoglobulin levels, IgG1; profile of Th2 cytokines such as IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-ß; inflammatory infiltrate e) absence of eosinophilia in BAL; T cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. The insulin treatment restored all parameters studied. Therefore, they suggest that insulin modulates late pulmonary allergic inflammation in diabetic mice
Asunto(s)
Animales , Masculino , Ratones , Asma , Inflamación/complicaciones , Insulina/análisis , Hiperreactividad Bronquial , Diabetes Mellitus/clasificaciónRESUMEN
OBJECTIVE: To examine the effect of metanol extract of Petiveria alliacea (PM) on airway inflflammation in a murine model of chronic asthma. METHODS: Two-month-old male BALB/c mice (n=6-8/group) were sensitized on days 0 and 14 by intraperitoneal injection of 20 µg ovalbumin (OVA). On day 25, the mice received an airway challenge with OVA (3%, w/v, in phosphate buffered saline). PM was administered orally by oral gavage to mice at doses of 100, 200 and 400 mg/kg body weight once daily from days 18 to 23. Control mice were orally administered phosphate buffered saline (PBS) to induce a model of asthma. At the end of the test, respiratory reactivity was assayed, the total cell number, interleukin-4 (IL-4), IL-5, IL-13, tumor necrosis factor-alpha (TNF-α) and reactive oxygen species (ROS) in the bronchoalveolar lavage fluid (BALF) were determined and the levels of serum IgE, intercellular cell adhesion molecule 1 (ICAM-1) and eotoxin were measured. In addition, lung tissue was used to qualify the IL-4, IL-5, IL-13, TNF-α and transforming growth factor beta 1 (TGF-ß1). Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS: The administration of PM in comparison with the OVA-only treated group signifificantly attenuated the infifiltration of eosinophils and other inflflammatory cells (P<0.01). Airway resistance (RI) in the OVA-only induced group was significantly higher than that of the PBS control group (P<0.01) when methacholine was added. TNF-α, IgE, TGF-ß1 and cytokine levels IL-4, IL-5, IL-13 in the BALF decreased compared to control mice (P<0.01 or P<0.05). PM treatment also inhibited the production of chemokines, eotaxin and ICAM-1 in BALF (P<0.01), which improved lung function. Histopathological examination revealed that the sensitized treated PM groups had significant lower in inflammatory scores similar to dexamethasone treatments and the untreated group. CONCLUSION: Administration of PM could inhibit airway inflammation, regulate cytokines, chemokines and enhance pulmonary conditions in allergic murine model of asthma.
Asunto(s)
Alérgenos/inmunología , Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Pulmón/patología , Ovalbúmina/inmunología , Phytolaccaceae/química , Extractos Vegetales/uso terapéutico , Células Th2/inmunología , Animales , Asma/sangre , Asma/inmunología , Asma/fisiopatología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina E/sangre , Inflamación/sangre , Inflamación/complicaciones , Inflamación/inmunología , Pulmón/inmunología , Pulmón/fisiopatología , Masculino , Metanol , Ratones Endogámicos BALB C , Moco/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. AIMS OF THE STUDY: To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. MATERIALS AND METHODS: Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. RESULTS: Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200â¯mgâ¯kg-1, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200â¯mgâ¯kg-1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100â¯mgâ¯kg-1 respectively. CONCLUSION: The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma.
Asunto(s)
Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Uña de Gato , Extractos Vegetales/uso terapéutico , Ácidos Carbocíclicos/análisis , Ácidos Carbocíclicos/farmacología , Ácidos Carbocíclicos/uso terapéutico , Alérgenos/inmunología , Animales , Antiasmáticos/análisis , Antiasmáticos/farmacología , Antiinflamatorios/análisis , Antiinflamatorios/farmacología , Asma/inmunología , Hiperreactividad Bronquial/inmunología , Líquido del Lavado Bronquioalveolar , Supervivencia Celular/efectos de los fármacos , Citocinas/inmunología , Modelos Animales de Enfermedad , Alcaloides Indólicos/análisis , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Pulmón/efectos de los fármacos , Pulmón/inmunología , Ratones , Ovalbúmina/inmunología , Fitoterapia , Corteza de la Planta , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Hojas de la Planta , Células RAW 264.7RESUMEN
OBJECTIVE: There is no standard definition of asthma for epidemiological purposes; most surveys use symptoms and bronchial hyperresponsiveness. Few studies tested mannitol challenge test (MCT) in occupational settings. We sought to determine efficacy and safety of MCT in detecting subjects with asthma symptoms in the workplace. METHODS: In this cross-sectional study we recruited 908 workers in 2 universities; they underwent a respiratory questionnaire, spirometry, skin prick tests, and MCT. RESULTS: Eight hundred and eleven subjects completed the study; 11.1% had a positive MCT; 8.14% had asthma. MCT had low sensitivity (35.4-61.9%) but high specificity (90.2-94.9%) to detect symptomatic individuals. The most prevalent symptom was wheezing in the last 12 months. Twenty-four of those with a positive MCT (26.7%) had no positive replies to the questions on asthma symptoms. Among subjects with a positive MCT, 71.9% achieved 95% of baseline FEV1 after 15 minutes of salbutamol recovery treatment. Nine subjects (1.1%) had adverse events that prevented the test from being completed. CONCLUSIONS: MCT has high specificity but low sensitivity to detect symptomatic subjects in the workplace. It may detect subjects with hyperresponsiveness but no symptoms, who could be at risk of developing airway diseases. The test is safe and well tolerated.
Asunto(s)
Asma/diagnóstico , Asma/epidemiología , Manitol/administración & dosificación , Lugar de Trabajo , Adulto , Animales , Animales de Laboratorio/inmunología , Brasil/epidemiología , Hiperreactividad Bronquial/diagnóstico , Pruebas de Provocación Bronquial/métodos , Estudios Transversales , Femenino , Humanos , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/epidemiología , Pruebas Intradérmicas , Masculino , Persona de Mediana Edad , Exposición Profesional , Prevalencia , Sensibilidad y Especificidad , Espirometría , UniversidadesRESUMEN
Ovalbumin-induced allergic lung inflammation (ALI) is a condition believed to be mediated by cytokines, extracellular matrix remodeling, and redox imbalance. In this study, we evaluated pulmonary function together with inflammatory markers as interleukin-4 (IL-4), myeloperoxidase (MPO), eosinophil cells, and redox markers in the lungs of BALB/c mice after ovalbumin (OVA) sensitization and challenge. Our results showed an increase in bronchial hyperresponsiveness stimulated by methacholine (Mch), inflammatory cell influx, especially eosinophils together with an increase of high mobility group box 1 (HMGB1) and altered lipid peroxidation (LP) and antioxidant defenses in the OVA group compared to the control group (p ≤ 0.5). Thus, we demonstrated that OVA-induced ALI altered redox status concomitantly with impaired lung function, which was associated with HMGB1 expression and proteolytic remodeling. Taken together all results found here, we may suggest HMGB1 is an important therapeutic target for asthma, once orchestrates the redox signaling, inflammation, and remodeling that contribute to the disease development.