RESUMO
Patients with cystic fibrosis (CF) often suffer from gastrointestinal cramps and intestinal obstruction. The CF transmembrane conductance regulator (CFTR) channel has been shown to be expressed in vascular and airway smooth muscle (SM). We hypothesized that the absence of CFTR expression alters the gastrointestinal SM function and that these alterations may show strain-related differences in the mouse. The aim of this study was to measure the contractile properties of the ileal SM in two CF mouse models. CFTR(-/-) and CFTR(+/+) mice were studied on BALB/cJ and C57BL/6J backgrounds. Responsiveness of ileal strips to electrical field stimulation (EFS), methacholine (MCh), and isoproterenol was measured. The mass and the cell density of SM layers were measured morphometrically. Finally, the maximal velocity of shortening (Vmax) and the expression of the fast (+)insert myosin isoform were measured in the C57BL/6J ileum. Ileal hyperreactivity was observed in response to EFS and MCh in CFTR(-/-) compared with CFTR(+/+) mice in C57BL/6J background. This latter observation was not reproduced by acute inhibition of CFTR with CFTR(inh)172. BALB/cJ CFTR(-/-) mice exhibited a significant increase of SM mass with a lower density of cells compared with CFTR(+/+), whereas no difference was observed in the C57BL/6J background. In addition, in this latter strain, ileal strips from CFTR(-/-) exhibited a significant increase in Vmax compared with control and expressed a greater proportion of the fast (+)insert SM myosin isoform with respect to total myosin. BALB/cJ CFTR(-/-) ilium had a greater relaxation to isoproterenol than the CFTR(+/+) mice when precontracted with EFS, but no difference was observed in response to exogeneous MCh. In vivo, the lack of CFTR expression induces a different SM ileal phenotype in different mouse strains, supporting the importance of modifier genes in determining intestinal SM properties.
Assuntos
Fibrose Cística/patologia , Íleo/patologia , Músculo Liso/patologia , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Animais , Western Blotting , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/fisiologia , Estimulação Elétrica , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Agonistas Muscarínicos/farmacologia , Contração Muscular/efeitos dos fármacos , Tono Muscular/efeitos dos fármacos , Cadeias Pesadas de Miosina/metabolismoRESUMO
Follow-up after thoracic aortic repair relies on CT and MR imaging in order to detect complications from the treatment or underlying pathology. Following prosthetic repair of the ascending aorta, peri-prosthetic hematoma and anastomotic complications (leak, false aneurysm, peri-prosthetic circulation) should be excluded. Following treatment with a covered stent, the location of the prosthesis and its skeleton should be evaluated and endo-leaks and wall defects should be excluded. Following treatment of a dissection, there often is persistent flow in the false lumen. The entry points into the false lumen should be identified. The caliber of the aorta at different levels should be assessed. Signs of ischemia (static and dynamic) and acute complications should be excluded in patients with acute chest pain. Atherosclerosis and dysplastic conditions may affect other segments of the aorta (aneurysm, dissection, hematoma). Follow-up is performed with CT, if possible, when high-resolution evaluation is required, of with MRI in other cases. Follow-up is obtained on a yearly basis or twice a year when an evolutive process is identified. It is performed every two to five years when the risk is low. Follow-up should be suggested by the radiologist.
Assuntos
Aorta Torácica/cirurgia , Doenças da Aorta/diagnóstico , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/diagnóstico , Tomografia Computadorizada por Raios X , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Feminino , HumanosRESUMO
BACKGROUND: The remodelling of airway smooth muscle (ASM) associated with asthma severity may involve the migration of ASM cells towards the epithelium. However, little is known about the mechanisms of cell migration and the effect of epithelial-derived mediators on this process. OBJECTIVE: The main objective of the current study is to assess the effects of epithelial-derived chemokines on ASM cell migration. METHODS: Normal human ASM cells were incubated with supernatants from cells of the bronchial epithelial cell line BEAS-2B and normal human bronchial epithelial (NHBE) cells. To induce chemokine production, epithelial cells were treated with TNF-alpha. Chemokine expression by epithelial cells was evaluated by quantitative real-time PCR, ELISA and membrane antibody array. To identify the role of individual chemokines in ASM cell migration, we performed migration assays with a modified Boyden chamber using specific neutralizing antibodies to block chemokine effects. RESULTS: Supernatants from BEAS-2B cells treated with TNF-alpha increased ASM cell migration; migration was increased 1.6 and 2.5-fold by supernatant from BEAS-2B cells treated with 10 and 100 ng/mL TNF-alpha, respectively. Protein levels in supernatants and mRNA expression by BEAS-2B cells of regulated on activation, normal T cell expressed and secreted (RANTES) and IL-8 were significantly increased by 100 ng/mL TNF-alpha treatment. The incubation of supernatant with antibodies to RANTES or IL-8 significantly reduced ASM cell migration, and the combined antibodies further inhibited the cell migration. The migratory effects of supernatants and inhibiting effects of RANTES and/or IL-8 were confirmed also using NHBE cells. CONCLUSION: The results show that chemokines from airway epithelial cells cause ASM cell migration and might potentially play a role in the process of airway remodelling in asthma.
Assuntos
Brônquios/citologia , Movimento Celular , Quimiocinas/metabolismo , Epitélio/metabolismo , Músculo Liso/citologia , Brônquios/imunologia , Células Cultivadas , Quimiocina CCL5/imunologia , Quimiocina CCL5/metabolismo , Epitélio/imunologia , Humanos , Interleucina-8/imunologia , Interleucina-8/metabolismo , Músculo Liso/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: Cat scratch disease is an infection caused by Bartonella henselae. The main clinical form is a lymphadenopathy with fever. However, uncommon bone involvement has been described. CASE REPORT: In this paper, we report a case of osteomyelitis in a 13-year-old teenager infected with B. henselae. The diagnosis was made based on PCR only because the serology was negative. A literature review reports 65 cases of osteomyelitis due to cat scratch disease. For each case, serology and PCR were notified. CONCLUSION: Osteomyelitis caused by B. henselae is a rare clinical manifestation. The diagnosis can be difficult, but the medical history must be accurate to search for contact with a cat and a cat scratch.
Assuntos
Doença da Arranhadura de Gato , Osteomielite/microbiologia , Adolescente , Feminino , HumanosRESUMO
1. The aim of the present work was to investigate under which circumstances atrial natriuretic peptide (ANP) modulates airway resistance. 2. Of the six groups of rabbits (n = 5) studied, three received an infusion of ANP (80 ng min-1 kg-1 i.v.) for a period of 100 min, while the other three were infused with the vehicle. Before receiving the infusion of ANP or the vehicle, the animals were pretreated with atropine (0.5 mg kg-1 i.v.), propranolol (2 mg kg-1 i.v.) or not pretreated. After 75 min of infusion of ANP, bronchoconstriction was induced by inhalation of histamine. Respiratory resistance (Rrs) was measured before and 3, 5, 10, 15 and 20 min post-histamine challenge. 3. Following 75 min of ANP infusion, plasma ANP concentration increased from 153 +/- 52 (mean +/- s.e.mean) to 1441 +/- 203 pg ml-1 (P < 0.05) without affecting baseline Rrs. Control Rrs values (12.5-20.4 cmH2O l-1 s) were significantly increased following the inhalation of histamine (P < 0.001). By themselves, atropine, propranolol or ANP did not modify the histamine-induced increase in Rrs. However, when the animals were pretreated with atropine, ANP infusion significantly reduced the increase in Rrs induced by histamine (30 +/- 2 vs 51 +/- 6 cmH2O l-1 s; P < 0.05). 4. These data suggest that ANP has an indirect modulating effect on the airway smooth muscle and will decrease Rrs when muscarinic receptors are blocked.
Assuntos
Fator Natriurético Atrial/farmacologia , Receptores Muscarínicos/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Fator Natriurético Atrial/sangue , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Broncoconstrição/efeitos dos fármacos , Histamina/farmacologia , Masculino , Músculo Liso/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Coelhos , Testes de Função Respiratória , Simpatolíticos/farmacologiaRESUMO
OBJECTIVE: To assess the etiologic role of maternal short stature, low pre-pregnancy body mass index (BMI), and low rate of gestational weight gain in idiopathic preterm labor. METHODS: We carried out a three-center case-control study of 555 women with idiopathic onset of preterm labor (before 37 completed weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases with early preterm labor (before 34 completed weeks) and cases with recurrent preterm labor (before 37 completed weeks plus a history of prior preterm delivery or second-trimester miscarriage). Controls were matched to cases by race and smoking history. All subjects responded in person to questions about height, pre-pregnancy weight, gestational weight gain, and obstetric and sociodemographic histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight gain demonstrated excellent test-retest reliability, with intra-class correlation coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses, women with a height of 157.5 cm or less had an increased risk of idiopathic preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09-2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI 1.16-2.62). Conditional logistic regression models containing all three anthropometric variables and controlling for parity, marital status, language, age, and education yielded virtually identical point estimates and CIs. CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of gestational weight gain may lead to shortened gestation by increasing the risk of idiopathic preterm labor.
Assuntos
Constituição Corporal , Trabalho de Parto Prematuro/etiologia , Antropometria , Estatura , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Idade Materna , Razão de Chances , Gravidez , Fatores de Risco , Aumento de PesoRESUMO
Although it is well known that hypoxemia induces pulmonary vasoconstriction and vascular remodeling, due to the proliferation of both vascular smooth muscle cells and fibroblasts, the effects of hypoxemia on airway smooth muscle cells are not well characterized. The present study was designed to assess the in vitro effects of hypoxia (1 or 3% O(2)) on rat airway smooth muscle cell growth and response to mitogens (PDGF and 5-HT). Cell growth was assessed by cell counting and cell cycle analysis. Compared with normoxia (21% O(2)), there was a 42.2% increase in the rate of proliferation of cells exposed to 3% O(2) (72 h, P = 0.006), as well as an enhanced response to PDGF (13.9% increase; P = 0.023) and to 5-HT (17.2% increase; P = 0.039). Exposure to 1% O(2) (72 h) decreased cell proliferation by 21.0% (P = 0.017) and reduced the increase in cell proliferation induced by PGDF and 5-HT by 16.2 and 15.7%, respectively (P = 0.019 and P = 0.011). A significant inhibition in hypoxia-induced cell proliferation was observed after the administration of bisindolylmaleimide GF-109203X (a specific PKC inhibitor) or downregulation of PKC with PMA. Pretreatment with GF-109203X decreased proliferation by 21.5% (P = 0.004) and PMA by 31.5% (P = 0.005). These results show that hypoxia induces airway smooth muscle cell proliferation, which is at least partially dependent on PKC activation. They suggest that hypoxia could contribute to airway remodeling in patients suffering from chronic, severe respiratory diseases.
Assuntos
Hipóxia/patologia , Músculo Liso/patologia , Traqueia/patologia , Animais , Becaplermina , Ciclo Celular , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Hipóxia/enzimologia , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Endogâmicos F344 , Serotonina/farmacologia , Traqueia/enzimologiaRESUMO
The aim of this work was to establish the role of endogeneous ANP during a spontaneous asthma attack. Forced expiratory lung volume in 1 s (FEV1), cardiovascular parameters, and plasma ANP, cAMP, and cGMP were measured for 60 min before and 10 min after treatment with a bronchodilator in 10 asthmatics. The results show that in the presence of moderate bronchoconstriction, FEV1 was 54 +/- 3% (+/-SE); ANP levels initially were slightly elevated at 47 +/- 10 pg/ml and decreased to 26 +/- 3 pg/ml (p < 0.05) over 60 min, with no change in FEV1. Following salbutamol inhalation, FEV1 increased to 77 +/- 4% with no change in ANP. We conclude that endogenous ANP does not act as a bronchodilator in asthmatics with moderate bronchospasm.
Assuntos
Albuterol/uso terapêutico , Asma/sangue , Fator Natriurético Atrial/sangue , Brônquios/fisiopatologia , Doença Aguda , Adulto , Análise de Variância , Asma/tratamento farmacológico , Asma/fisiopatologia , Fator Natriurético Atrial/fisiologia , Feminino , Humanos , MasculinoRESUMO
The effect of atrial natriuretic peptide (ANP) on histamine-induced bronchoconstriction was studied in vivo (in normoxic and in hypoxic rabbits) and in vitro. Thirty-two anesthetized rabbits, spontaneously breathing room air or 10% O2, received infusions of ANP (20, 40, or 80 ng/min/kg normoxia; 20 ng/min/kg hypoxia) or the vehicle for 100 min. After 75 min of ANP infusion, bronchoconstriction was induced inhaling histamine; respiratory resistance (Rrs) was measured prior to and until 20 min posthistamine. The results show that the histamine-induced increase in Rrs was significantly reduced by ANP 80 ng/kg/min in normoxia, and by ANP 20 ng/kg/min in hypoxia. In vitro, ANP had no effect on tracheal and bronchial smooth muscle precontracted with histamine or acetylcholine. These results show that ANP can decrease a histamine-induced bronchoconstriction in vivo but not in vitro, suggesting an indirect mechanism of action.
Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Asma/tratamento farmacológico , Fator Natriurético Atrial/farmacologia , Broncodilatadores/farmacologia , Anestésicos , Animais , Fator Natriurético Atrial/sangue , Broncodilatadores/sangue , Modelos Animais de Doenças , Técnicas In Vitro , Masculino , Oxigênio/farmacologia , CoelhosRESUMO
The aim of this work was to establish whether a physiological increase in atrial natriuretic peptide (ANP) plasma levels affects pulmonary gas exchange in humans. Ten volunteers received an infusion of either ANP (4 pmol.kg-1.min-1) or physiological saline, for 60 min. Baseline measures of the alveolar-arterial PO2 difference and of the physiological dead space were within normal limits and remained stable during and after the infusion of ANP or saline, although plasma ANP and cGMP rose significantly (p < 0.01) (mean +/- SEM: ANP: 13.4 +/- 3.9 to 56.0 +/- 10.4 pmol/l; cyclic GMP: 3.8 +/- 0.3 to 17.0 +/- 3.8 nmol/l). We conclude that a physiological increase in plasma ANP does not affect pulmonary gas exchange significantly in humans.
Assuntos
Fator Natriurético Atrial/fisiologia , Troca Gasosa Pulmonar , Adulto , Humanos , Infusões Intravenosas , Masculino , Valores de Referência , Método Simples-CegoRESUMO
Over the last fifty years, the role of neurogenic factors in asthma and bronchial hyperreactivity has been intensively investigated. The roles of the cholinergic and adrenergic nervous systems have been clarified and several sub-types of muscarinic receptors identified. The localisation and functions of both muscarinic and adrenergic receptors have been further specified. It has also been shown that afferent nerve fibers as well as sympathetic and parasympathetic nerve fibers secrete various neuropeptides. The physiological role of these peptides is not yet known but it appears that they have a powerful effect on bronchial smooth muscle tone, microvascular permeability, mucus secretion and secretion of mediators by inflammatory cells. The results of numerous studies suggest that there are several abnormalities in the adrenergic and cholinergic nervous systems of asthmatic patients, but that these abnormalities are not themselves the cause of bronchial hyperreactivity. They may however contribute to enhance it. The role of the various newly identified neuropeptides in the genesis and maintenance of bronchial hyperreactivity remains to be determined.
Assuntos
Asma/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Hiper-Reatividade Brônquica/fisiopatologia , Fibras Adrenérgicas/fisiologia , Vias Aferentes/fisiopatologia , Asma/imunologia , Hiper-Reatividade Brônquica/imunologia , Permeabilidade Capilar/fisiologia , Fibras Colinérgicas/fisiologia , Humanos , Inflamação , Muco/metabolismo , Músculo Liso/fisiopatologia , Neuropeptídeos/metabolismo , Receptores Adrenérgicos/fisiologia , Receptores Muscarínicos/classificação , Receptores Muscarínicos/fisiologiaRESUMO
PURPOSE: To assess clinical outcomes of blunt splenic injuries (BSI) managed with proximal versus distal versus combined splenic artery embolization (SAE). MATERIALS AND METHODS: All consecutive patients with BSI admitted to our trauma centre from 2005 to 2010 and managed with SAE were reviewed. Outcomes were compared between proximal (P), distal (D) or combined (C) embolization. We focused on embolization failure (splenectomy), every adverse events occurring during follow up and material used for embolization. RESULTS: Fifty patients were reviewed (P n = 18, 36%; D n = 22, 44%; C n = 8, 16%). Mean injury severity score was 20. The technical success rate was 98%. Four patients required splenectomy (P n = 1, D n = 3, C n = 0). Clinical success rate for haemostasis was 92% (4 re-bleeds: P n = 2, D n = 2, C n = 0). Outcomes were not statistically different between the materials used. Adverse events occurred in 65% of the patients during follow up. Four percent of the patients developed major complications and 56% developed minor complications attributable to embolization. There was no significant difference between the 3 groups. CONCLUSION: SAE had an excellent success rate with adverse events occurring in 65% of the patients and no significant differences found between the embolization techniques used. Proximal preventive embolization appears to protect in high-grade traumatic injuries.
Assuntos
Embolização Terapêutica/métodos , Artéria Esplênica , Ruptura Esplênica/terapia , Ferimentos não Penetrantes/terapia , Adolescente , Adulto , Idoso , Angiografia , Criança , Terapia Combinada , Embolização Terapêutica/efeitos adversos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenectomia , Ruptura Esplênica/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
The present manuscript is a summary of two lectures which were given respectively by B. Weynand and G.R. Ferretti. The new classification of lung adenocarcinomas has changed the view of the radiologists and the pathologists especially regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper is to correlate radiological and histopathological images according to the 2011 classification for lung adenocarcinoma proposed by the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society and to draw attention to the way these lesions can be approached preoperatively.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tomografia por Emissão de Pósitrons/tendências , Tomografia Computadorizada por Raios X/tendências , Adenocarcinoma/classificação , Humanos , Neoplasias Pulmonares/classificaçãoRESUMO
Extracellular adenosine triphosphate (ATP) has a range of effects on a wide variety of cells through the activation of specific purinoceptors. The aim of this study was to establish whether P2 purinoceptors are present on airway smooth muscle cells. Experiments were conducted on cultured rat tracheal smooth-muscle cells (first through third passage). Intracellular Ca2+ ([Ca2+]i) was measured using Fura-2 and dual-excitation wavelength microfluorometry. The effects of ATP, adenosine diphosphate (ADP), uridine triphosphate (UTP), and adenosine (ADO) were measured in concentrations from 10(-6) to 10(-3) M. At a concentration of 10(-4) M, the peak [Ca2+]i was 502 +/- 92 nM for ATP and 543 +/- 76 nM for UTP (mean +/- standard error of the mean). ADO had no significant effect on Ca2+ release. Peak [Ca2+]i induced by ATP was not dependent on extracellular Ca2+ but was blocked by U-73122, an inhibitor of phospholipase C. Pretreatment with adenosine deaminase and desensitization with alphabeta-MeATP had no effect on ATP-induced Ca2+ release. The effects of ATP (10(-4) M) on peak [Ca2+]i were potentiated by the presence of ADO 10(-5) M (969 +/- 257 nM; P < 0.05). The presence of XAC, a blocker of A1 and A2 ADO receptors did not prevent this effect. In the presence of XAC, ADO 10(-6) M potentiated the effects of ATP (peak [Ca2+]i: 1,300 +/- 229 nM). The addition of 1433U83, a blocker of A3 ADO receptors, blocked the synergistic effect of ADO 10(-6) M on ATP. These data show that P2 purinoceptors, most likely of the P2U subtype, are present on airway smooth muscle cells and that the newly discovered A3 ADO receptor appears to be also present.
Assuntos
Cálcio/metabolismo , Nucleosídeos de Purina/farmacologia , Nucleotídeos de Purina/farmacologia , Traqueia/efeitos dos fármacos , Animais , Citosol/efeitos dos fármacos , Citosol/metabolismo , Masculino , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Ratos , Ratos Endogâmicos F344 , Receptores Purinérgicos P2/metabolismo , Traqueia/citologia , Traqueia/metabolismoRESUMO
The effect of increasing doses of dopamine (inhaled or infused) on pulmonary resistance (RL) was measured in 4 normal and in 4 asthmatic subjects. Dopamine, in doses sufficient to raise systolic blood pressure 25 mmHg, did not change RL. However, dopamine, inhaled and infused, significantly decreased histamine-induced bronchoconstriction both in normal and in asthmatic subjects. Thus, we conclude that if dopamine is released by the adrenal medulla during an asthmatic attack, it should have a beneficial rather than a deleterious effect.
Assuntos
Brônquios/efeitos dos fármacos , Dopamina/farmacologia , Músculo Liso/efeitos dos fármacos , Adulto , Resistência das Vias Respiratórias , Asma/diagnóstico , Asma/fisiopatologia , Brônquios/fisiopatologia , Testes de Provocação Brônquica , Feminino , Volume Expiratório Forçado , Histamina , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiopatologiaRESUMO
We estimated the number of mast cells in monkey lungs by both quantitative histologic examination and measurement of total lung histamine, and showed that monkey lungs contain between 10(7) and 10(8) mast cells, with approximately 83% of these being located in conducting airways, and 17% in the parenchyma. The number of mast cells found in each airway generation increased from approximately 60,000 in the trachea to 8 million in the terminal bronchioles. In airways from different generations the number of mast cells superficial to the basement membrane in the epithelium and lumen (EMC) was compared to the number of mast cells found in the submucosa between basement membrane and cartilage and to the number of those found outside the cartilage. The number of EMC varied between animals and ranged from 0-0.4% of the total number of mast cells in the trachea, to 0-27% of the total in the terminal bronchioles. On the average, EMC accounted for 12% of the total number of mast cells in conducting airways, where we calculate that there is approximately one EMC for every 100,000 epithelial cells. Eosinophils were distributed in close relation to mast cells in the mucosa and submucosa, but were rare outside the cartilage. We conclude that the number of mast cells increases from central to peripheral airways and that this may account for the marked peripheral airway response observed after antigen challenge.
Assuntos
Pulmão/imunologia , Macaca fascicularis/imunologia , Macaca/imunologia , Mastócitos , Animais , Brônquios/citologia , Brônquios/imunologia , Contagem de Células , Eosinófilos , Células Epiteliais , Haplorrinos , Histamina/análise , Pulmão/análise , Pulmão/citologia , Mucosa/citologia , Mucosa/imunologia , Traqueia/citologia , Traqueia/imunologiaRESUMO
Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.
Assuntos
Asma/fisiopatologia , Resistência das Vias Respiratórias , Animais , Reações Antígeno-Anticorpo , Asma/imunologia , Brônquios/fisiopatologia , Permeabilidade da Membrana Celular , Modelos Animais de Doenças , Haplorrinos , Liberação de Histamina , Humanos , Imunoglobulina E , Macaca mulatta , Mastócitos/imunologia , Mecanorreceptores/fisiopatologia , Mucosa/fisiopatologia , ReflexoRESUMO
In view of the fact that the inhomogeneity effects on pulmonary diffusing capacity (DL) estimates are quite different for O2 and for CO, simultaneous determinations of steady-state DLCO and DLO2 were attempted and compared. To this end, pulmonary gas exchange was measured in 17 anesthetized and artificially ventilated dogs, in hypoxia with and without carbon monoxide in inspired gas (FIO2 = 0.12, FICO = 0.0009 to 0.0016). The diffusing capacity estimates were computed by two conventional procedures, the first (Dapp) taking into account the mean alveolar partial pressures and the second (DVDA) the ideal alveolar partial pressures. It was found that the presence of COHb in blood, inevitable in the steady-state DLCO procedure, leads to a marked underestimation of DLO2; therefore DLCO values could only be adequately compared to DLO2 values obtained in the absence of CO from inspired gas. These DLO2 were 18.5 and 33.4 mumol . min-1 . Torr-1 . kg-1 for the mean DappO2 and DVDAO2, respectively, whereas the DLCO values obtained after 15 to 25 min CO inspiration were 30.0 and 83.4 mumol . min-1 . Torr-1 . kg-1 for the mean DappCO and the mean DVDACO, respectively. The salient feature is that with both procedures the mean value of DLCO estimate is higher than the corresponding DLO2 estimate. This finding suggests that in anesthetized, artificially ventilated dogs DappO2 and DVDACO estimates obtained by steady-state procedures in hypoxia are largely influenced by inhomogeneity effects and of limited value for assessment of the diffusing properties of the lung. DappCO and DVDAO2 are also affected by inhomogeneities but to a lesser degree.
Assuntos
Dióxido de Carbono , Oxigênio , Capacidade de Difusão Pulmonar , Animais , Cães , Hipóxia/fisiopatologia , MatemáticaRESUMO
The aim of this work was to determine if the nonadrenergic noncholinergic nervous system can be reflexly activated in asthmatic patients by stimulating the vocal cords. The stimulation was produced by a cytology brush passed through a bronchoscope previously introduced transnasally and positioned just above the epiglottis. The subjects were premedicated with cholinergic blockers, and bronchoconstriction was induced by inhalation of histamine. In 11 experiments performed on six patients, vocal cords stimulation resulted in a decreased RL from 8.4 +/- 1.0 to 6.3 +/- 0.8 cm H2O.L-1.s (mean +/- SE) (p less than 0.01). To assess the possible contribution of circulating catecholamines to this decrease, plasma epinephrine and norepinephrine levels were measured in six experiments, before and 30 s, 1, 3, and 5 min after the stimulation. Pulmonary resistance fell from 10.0 +/- 1.3 to 7.6 +/- 0.9 cm H2O.L-1.s (mean +/- SE) (p less than 0.05) 30 s and to 7.9 +/- 0.9 cm H2O.L-1.s (p less than 0.05) 60 s after stimulation. Epinephrine and norepinephrine levels increased slightly but not significantly throughout the experiment. We conclude that in asthmatic patients, as in normal subjects, stimulation of the vocal cords produces a reflex decrease in histamine-induced bronchoconstriction which is modulated by the nonadrenergic noncholinergic nervous system.
Assuntos
Asma/fisiopatologia , Brônquios/fisiopatologia , Histamina/farmacologia , Laringe/fisiopatologia , Reflexo/fisiologia , Administração por Inalação , Adulto , Asma/sangue , Sistema Nervoso Autônomo/fisiopatologia , Brônquios/efeitos dos fármacos , Brônquios/inervação , Epinefrina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Estimulação FísicaRESUMO
The aims of this work were: (1) to establish a technique for the sampling of human tracheobronchial mucus not contaminated by saliva or topical anesthesia, and (2) to measure its viscoelastic properties. After local anesthesia of the hypopharynx by topical application of 4% xylocaine, a double-sleeve microbiology specimen brush was introduced into a flexible bronchoscope placed in the trachea. The brush was left in direct contact with the bronchial mucosa for 20 to 30 s to allow mucus to collect on it. The mucus sample was then scraped from the brush and immediately covered with paraffin oil. Its viscoelastic properties were determined by the magnetic microrheometer technique. Excluding the time to anesthetize, the whole procedure took less than 1 min (thus minimizing the effect of cough) and resulted in sufficient mucus for rheologic analysis in approximately 90% of trials, i.e., 2.1 +/- 1.5 (SD) mg. Mucus specimens were collected from 20 fasting healthy nonsmoking subjects; 17 of them returned for a second collection several days later. Values for mucus mechanical impedance (vector sum of elasticity and viscosity) at 1 rad/s were: Control 1, 141 +/- 41 (SE); Control 2, 155 +/- 58 dyn/cm2. There was a large variation in mucus viscoelasticity, both between subjects (CV, 130%) and within the same subject (CV, 55%) on different days. In 7 subjects, mucus samples were collected 15 min after intravenous injection of 0.6 mg atropine. Viscoelasticity in these samples was 708 +/- 147 dyn/cm2, a value significantly different from Control 1 (p less than 0.05) and Control 2 (p less than 0.05) values.(ABSTRACT TRUNCATED AT 250 WORDS)