RESUMEN
Sulfonamides are a family of synthetic drugs with a broad-spectrum of antimicrobial activity. Like other antimicrobials, they have been found in aquatic environments, making their detection important. Herein, an electrochemical sensor was designed using tannic acid exfoliated few-layered MoS2 sheets, which were combined with a mixture of reduced graphene oxide (rGO) and graphite flakes (G). The rGO/G was formed using electrodeposition, by cycling from -0.5 to -1.5 V in an acidified sulfate solution with well dispersed GO and G. The exfoliated MoS2 sheets were drop cast over the wrinkled rGO/G surface to form the final sensor, GCE/rGO/G/ta-MoS2. The mixture of rGO/G was superior to pure rGO in formulating the sensor. The fabricated sensor exhibited an extended linear range from 0.1 to 566 µM, with a LOD of 86 nM, with good selectivity in the presence of various salts found in water and structurally related drugs from the sulfonamide family. The sensor showed very good reproducibility with the RSD at 0.48 %, repeatability and acceptable long term stability over a 10-day period. Good recovery from both tap and river water was achieved, with recovery ranging from 90.4 to 98.9 % for tap water and from 83.5 to 94.4 % for real river water samples.
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Grafito , Nanocompuestos , Polifenoles , Molibdeno , Técnicas Electroquímicas , Reproducibilidad de los Resultados , Sulfanilamida , AguaRESUMEN
Korea has recently experienced an increasing number of acute hepatitis A cases. We investigated the dynamics of hepatitis A and changes in the mean age of patients in a hospital in Seoul, Korea. Mean age increased consistently from 19 years in 1996 to 30 years in 2009 (P < 0·0001). Between two acute hepatitis A outbreaks in 1998-1999 and in 2008-2009, mean age increased from 23 to 30 years (P < 0·001). However, the hepatitis A clinical outcomes were similar between the outbreaks. Duration of hospital stay, creatinine level and prothrombin time did not differ. Throughout the study period, individuals born in the 1970s and 1980s comprised the largest proportion (84%) of patients. As this susceptible generation ages, the mean age of hepatitis A patients in Korea will increase consistently. However, at present, the impact of increasing age on clinical outcomes is not apparent.
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Anticuerpos de Hepatitis A/sangre , Virus de la Hepatitis A Humana/inmunología , Hepatitis A/sangre , Hepatitis A/epidemiología , Lesión Renal Aguda/epidemiología , Adolescente , Adulto , Distribución por Edad , Alanina Transaminasa/sangre , Análisis de Varianza , Bilirrubina/sangre , Niño , Preescolar , Creatinina/sangre , Femenino , Humanos , Incidencia , Lactante , Tiempo de Internación , Modelos Lineales , Masculino , Persona de Mediana Edad , Prevalencia , Tiempo de Protrombina , República de Corea/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.
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Tolerancia Inmunológica/efectos de los fármacos , Neoplasias/inmunología , Simvastatina/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Animales , Recuento de Células , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Citostáticos/farmacología , Citostáticos/uso terapéutico , Factores de Transcripción Forkhead/genética , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Humanos , Tolerancia Inmunológica/inmunología , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Interleucina-10/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Ratones , Ratones Endogámicos C57BL , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Simvastatina/uso terapéutico , Bazo/citología , Bazo/inmunología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Factor de Crecimiento Transformador beta/metabolismoAsunto(s)
Adenoma/cirugía , Neoplasias del Ciego/cirugía , Ciego/irrigación sanguínea , Colonoscopía/efectos adversos , Infarto/etiología , Intususcepción/etiología , Humanos , Infarto/diagnóstico , Infarto/cirugía , Intususcepción/diagnóstico por imagen , Intususcepción/cirugía , Masculino , Persona de Mediana Edad , RadiografíaAsunto(s)
Amiloidosis/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Duodenales/diagnóstico , Enfermedades Duodenales/tratamiento farmacológico , Femenino , Humanos , Enfermedades del Íleon/diagnóstico , Enfermedades del Íleon/tratamiento farmacológico , Infliximab , Persona de Mediana EdadRESUMEN
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a disease characterised by not fully reversible airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee decided to diagnose COPD using post-bronchodilator spirometry values. We aimed to examine the prevalence and risk factors of COPD in Ansan, an industrialised city of Korea, by using the post-bronchodilator GOLD criteria. We then investigated the implications of brenchodilation on the prevalence of COPD. DESIGN: A total of 3642 participants in the Korean Health and Genome Study were interviewed about age, income, smoking status and respiratory symptoms and completed pulmonary function tests, including postbronchodilator spirometry. RESULTS: COPD prevalence by post-bronchodilator spirometry was 3.7% (134/3642), which was significantly different from that estimated using pre-bronchodilator criteria (7.7%, 282/3642). Exclusion of subjects with significant bronchodilator response (BDR) significantly lowered the prevalence of COPD to 3.3% (117/3572), compared with including subjects with post-bronchodilatory residual obstruction with significant BDR. Prevalence was associated with old age, smoking history, male sex and respiratory symptoms. CONCLUSION: COPD prevalence by post-bronchodilator GOLD criteria was 3.7%, which was much lower than that of pre-bronchodilator criteria. The bronchodilator reversibility test substantially affects estimations of COPD prevalence.
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Broncodilatadores/administración & dosificación , Broncoespirometría , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adulto , Anciano , Femenino , Humanos , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Factores de Riesgo , Índice de Severidad de la EnfermedadAsunto(s)
Anafilaxia/inducido químicamente , Antitusígenos/efectos adversos , Hipersensibilidad a las Drogas/inmunología , Glicoles de Propileno/efectos adversos , Adulto , Anafilaxia/inmunología , Antihipertensivos/uso terapéutico , Prueba de Desgranulación de los Basófilos , Humanos , Masculino , Pruebas CutáneasRESUMEN
OBJECTIVE: To investigate the effect of interleukin (IL) 27 -964A/G, 2095T/G, 4603G/A and 4730T/C gene polymorphisms on the development of pulmonary tuberculosis (PTB), radiographic characteristics and severity. DESIGN: Differences in the allele and genotype distributions of the -964A/G, 2095T/G, 4603G/A and 4730T/C polymorphisms between 224 PTB patients and 233 healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavitation, were investigated. Serum IL-27 concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: There were no significant differences in the allele or genotype distributions between PTB patients and healthy controls. However, the -964A/A genotype was more prevalent in patients with single-lobe involvement than the -964A/G or -964G/G genotype in patients with multi-lobe involvement (50.0% vs. 31.3%, P = 0.01). There was no difference between patients with and without cavitation (P > 0.05). Serum median IL-27 concentration was significantly higher in patients with single-lobe involvement than in those with multi-lobe involvement (P = 0.03) and in those with -964A/A genotypes than in those with -964A/G or -964G/G genotypes (P = 0.02). CONCLUSIONS: In terms of serum IL-27 levels, the -964 A/A genotype may be associated with a protective role that prevents the intrapulmonary spread of PTB rather than its development.
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Interleucinas/genética , Polimorfismo de Nucleótido Simple , Tuberculosis Pulmonar/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Interleucinas/sangre , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Factores Protectores , Radiografía , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
OBJECTIVES: The possibility that a bronchial inflammatory process could be involved with a chronic nonproductive cough without other potential causes such as postnasal drip syndrome, bronchial asthma, gastroesophageal reflux, chronic bronchitis, bronchiectasis, or the use of angiotensin-converting enzyme inhibitors has not been clearly described. We investigated the possibility that a chronic nonproductive cough without other potential causes is associated with airway inflammation, and if this is so, what the relationship might be between this inflammation and the possible etiology of the cough. SUBJECTS: Twenty-five adults with chronic nonproductive cough as an isolated symptom over a 3-week period, and 5 healthy control subjects were studied. MEASUREMENTS AND RESULTS: Clinical assessments, cough scores, methacholine challenges, allergy skin prick tests, and bronchoscopies for bronchial biopsies were performed. In the bronchial biopsies, the patients were divided into the following two subgroups: 21 patients who were infiltrated with eosinophils vs the healthy control group (median, 12.0 vs. 0.0 cells/mm(2), respectively; p < 0.01); and 4 patients who were infiltrated with lymphocytes vs the healthy control group (median, 84.5 vs. 22.0 cells/mm(2), respectively; p < 0.01). With the methacholine challenge test, 5 of the 21 eosinophil-infiltrated patients received diagnoses of cough-variant asthma, and the other 16 patients received diagnoses of eosinophilic bronchitis. In the lymphocyte-infiltrated group, all four patients received diagnoses of lymphocytic bronchitis. CONCLUSIONS: These results suggest that a chronic nonproductive cough as an isolated symptom is associated with airway inflammation due to eosinophil and lymphocyte infiltration. The causes of the chronic nonproductive cough were eosinophilic bronchitis, cough-variant asthma, and lymphocytic bronchitis.
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Bronquitis Crónica/diagnóstico , Tos/etiología , Adulto , Biopsia , Bronquios/patología , Pruebas de Provocación Bronquial , Bronquitis Crónica/etiología , Bronquitis Crónica/patología , Tos/patología , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/etiología , Eosinofilia/patología , Femenino , Humanos , Recuento de Leucocitos , Linfocitosis/diagnóstico , Linfocitosis/etiología , Linfocitosis/patología , Masculino , Cloruro de Metacolina , Persona de Mediana EdadRESUMEN
BACKGROUND: Differential diagnosis of solitary pulmonary nodules (SPNs) can be difficult in areas, such as Korea, where tuberculosis is endemic. Nested polymerase chain reaction (PCR) is a widely used method to test a very small amount of pathogen and to detect Mycobacterium tuberculosis from fine needle aspirates. OBJECTIVES: The usefulness of nested PCR for the detection of M tuberculosis from tuberculous SPN and for the differential diagnosis of SPN was evaluated. METHODS: Thirty-three patients in whom a diagnosis of SPN was made based on a CT scan of the chest were enrolled in this study. Included were 17 malignant and 16 benign SPNs. Nested PCR was carried out for the detection of M tuberculosis by using TB-1, TB-2, TB-28, and TB-29C on fine needle aspirates from the nodule in all 33 cases. RESULTS: Aspirates from malignant neoplasms, pneumonia, and sequestration were all negative on nested PCR for tuberculosis. One of the three radiologically suspected tuberculous nodules without response to anti-tuberculosis drugs (uncertain) yielded positive results on nested PCR for the detection of M tuberculosis. In contrast, 7 out of 8 (87.5%) aspirates from proven tuberculous nodules showed positive results on nested PCR. Nested PCR could be used to detect M tuberculosis in fine needle aspirates from tuberculous SPNs with good sensitivity (87.5%) and specificity (96.0%). CONCLUSION: Nested PCR for the detection of M tuberculosis in fine needle aspirates may be useful in the differential diagnosis of SPNs.
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ADN Bacteriano/análisis , Mycobacterium tuberculosis/genética , Nódulo Pulmonar Solitario/microbiología , Tuberculosis Pulmonar/microbiología , Biopsia con Aguja , Líquido del Lavado Bronquioalveolar/microbiología , Cartilla de ADN/química , Diagnóstico Diferencial , Electroforesis en Gel de Agar , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/microbiología , Mycobacterium tuberculosis/aislamiento & purificación , Neumonía Bacteriana/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad , Nódulo Pulmonar Solitario/diagnóstico , Esputo/microbiología , Tomografía Computarizada por Rayos X , Tuberculosis Pulmonar/diagnósticoRESUMEN
SETTING: Nrampl encoded by the NRAMP1 gene influences the phagolysosomal function of alveolar macrophage against Mycobacterium tuberculosis. Genetic polymorphisms of NRAMP1 affect innate host resistance through the defective production and function of Nrampl. OBJECTIVE: To investigate this relationship, the NRAMP1 polymorphisms in patients with tuberculous pleurisy were determined. DESIGN: Pleural biopsy proven 56 patients were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. Three NRAMP1 polymorphisms such as single nucleotide change in intron 4(469 + 14G/C, INT4), a non-conservative single-base substitution at codon 543(D543N) and TGTG deletion in the 3' untranslated region (1729 + 55del4, 3'UTR) were determined. RESULTS: The frequencies of mutant genotypes of INT4 and 3'UTR were significantly high in the pleurisy group (P = 0.01, P = 0.02), but the frequencies of D543N were not significantly different between the two groups. Odds ratios (OR), which are a comparison of the wild with the mutant genotype, were 8.02 (95%CI 2.42 approximately 26.57) for INT4 and 5.73 (95%CI 1.14 approximately 28.92) for 3'UTR which were statistically significant. In the combined analysis of the INT4 and 3'UTR, the ORs were 6.00 (95%CI 1.46 approximately 24.64) for GC/++ genotype and 14.00 (95%CI 1.61 approximately 121.75) for GC/+del when compared with GG/++; these differences were statistically significant. CONCLUSION: The NRAMP1 genetic polymorphisms, especially INT4 and 3'UTR, were closely related to tuberculous pleurisy.
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Proteínas de Transporte de Catión/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Tuberculosis Pleural/genética , Adulto , Alelos , Secuencia de Bases , Estudios de Casos y Controles , Estudios de Cohortes , Intervalos de Confianza , Femenino , Frecuencia de los Genes , Humanos , Incidencia , Corea (Geográfico)/epidemiología , Masculino , Datos de Secuencia Molecular , Oportunidad Relativa , Reacción en Cadena de la Polimerasa/métodos , Probabilidad , Valores de Referencia , Factores de Riesgo , Sensibilidad y Especificidad , Tuberculosis Pleural/epidemiologíaRESUMEN
We present a case of non-specific interstitial pneumonia (NSIP) with reversed halo sign on thin-section CT. A 52-year-old female presented with a cough and New York Heart Association (NYHA) class 2 dyspnoea of 4 months duration. A chest radiograph showed poorly defined, patchy ground-glass opacities in both lungs. Thin-section CT demonstrated the reversed halo sign, which is a central ground-glass opacity surrounded by crescent or ring-shaped areas of consolidation in multifocal areas. Multifocal patchy ground-glass opacity and consolidation and enlarged paratracheal, hilar and subcarinal lymph nodes were also shown. Video-assisted thoracic surgical (VATS) lung biopsy was performed, and histopathology revealed cellular NSIP.
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Tos/diagnóstico por imagen , Disnea/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation. OBJECTIVE: To evaluate carotid artery intima-media thickness (IMT), high sensitivity C-reactive protein (hsCRP) and their correlation in newly diagnosed untreated patients with COPD. DESIGN: Post-bronchodilator spirometry, carotid artery IMT and blood tests were measured in patients with COPD (COPD group). Age, sex, body mass index, smoking status and smoking amount were compared with matched healthy subjects (non-COPD group). Participants taking medications and/or with a history of hypertension, diabetes mellitus, dyslipidaemia, COPD or cardiovascular disease were excluded. RESULTS: A total of 126 patients (COPD group 42, non-COPD group 84) were enrolled. The IMT and hsCRP of the COPD group were significantly higher than in the non-COPD group (P < 0.05). The decrease in the forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio and FEV(1) was significantly correlated with an increase in the hsCRP and IMT (P < 0.05); there was no correlation between the IMT and hsCRP (P = 0.152). CONCLUSION: In newly diagnosed untreated patients with COPD, the carotid artery IMT and hsCRP were significantly higher than in healthy subjects. These findings suggest that systemic inflammation may play a potential role in preclinical atherosclerosis in COPD.
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Proteína C-Reactiva/metabolismo , Enfermedades de las Arterias Carótidas/etiología , Inflamación/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/patología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado , Humanos , Inflamación/epidemiología , Inflamación/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
We examined the pattern of FtsZ localization in a Bacillus subtilis minCD mutant. When grown in minimal medium, the majority (approximately 89%) of the minCD mutant cells with an FtsZ ring had a single, medially positioned FtsZ ring. These results indicate that genes in addition to minCD function to restrict the number and position of FtsZ rings. When grown in rich medium, greater than 50% of the minCD mutant cells had multiple FtsZ rings, indicating significant differences in regulation of FtsZ ring formation based on growth medium.
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Adenosina Trifosfatasas/metabolismo , Bacillus subtilis/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas del Citoesqueleto , Proteínas de Escherichia coli , Adenosina Trifosfatasas/genética , Bacillus subtilis/genética , Bacillus subtilis/crecimiento & desarrollo , Proteínas Bacterianas/genética , Secuencia Conservada , Medios de Cultivo , Genes Bacterianos , MutaciónRESUMEN
We determined the vascular and airway effects of PGF2 alpha and its mechanism of action on isolated-perfused lungs of rats were isolated and perfused at 50 ml/kg/min with Krebs-Henseleit bicarbonate buffer solution containing 3% bovine serum albumin. The lungs were ventilated with 21% O2 and 5% CO2 at a tidal volume of 2 ml. frequency of 60 per minute and positive end expiratory pressure of 3 cmH2O. Following injection of 50 micrograms PGF2 alpha into the afferent pulmonary catheter, there was a marked rise in pulmonary arterial pressure (Ppa) and in resistance to airflow across the lung (RL) and a fall in dynamic lung compliance (Cdyn). Double vascular occlusion technique revealed that 29% of the rise in Ppa was due to an increase in upstream and 71% to downstream resistance. N omega-nitro-L-arginine, 100 microns, a NO synthase inhibitor potentiated the Ppa response two-fold with significant change in airway mechanics. Rat atrial natriuretic factor (r-ANF), 40 micrograms quickly reversed the changes in Ppa, RL and Cdyn. Infusion of r-ANF prior to PGF2 alpha attenuated the Ppa response by 38%, RL by 44% and Cdyn by 12%. SQ 29548, a thromboxane receptor blocker and Cl, a protein kinase C (PKC) inhibitor, fully blocked both the vascular and airway responses to PGF2 alpha. PGF2 alpha is a constrictor of pulmonary vessels and airways in rat lungs via thromboxane SQ 29548 receptors, thansduced by intracellular PKC.
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Factor Natriurético Atrial/farmacología , Broncoconstricción/efectos de los fármacos , Prostaglandinas F/farmacología , Circulación Pulmonar/efectos de los fármacos , Receptores de Tromboxanos/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Animales , Factor Natriurético Atrial/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/fisiología , Prostaglandinas F/administración & dosificación , Circulación Pulmonar/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de Tromboxanos/fisiología , Vasoconstricción/fisiologíaRESUMEN
PURPOSE: The aim of this study was to assess the CT findings of pulmonary involvement in patients with idiopathic hypereosinophilic syndrome (HES). METHOD: The study included five patients with idiopathic HES who had pulmonary involvement proven by bronchoalveolar lavage (n = 3) or based on clinical and radiologic findings (n = 2). Four patients had high resolution CT and one had conventional CT. The CT scans were retrospectively reviewed by two chest radiologists for pattern and distribution of disease. RESULTS: All five patients had several small nodules in both lungs at CT scan. Four patients had nodules with a halo of ground-glass attenuation. Three patients had focal areas of ground-glass attenuation in both lungs. These lesions were present in all lung zones and involved mainly the peripheral lung. There was neither lobar predilection nor peribronchovascular distribution. Other organs involved included bone marrow (n = 3), liver (n = 3), stomach (n = 1), and peritoneum (n = 1). CONCLUSION: The CT findings of pulmonary involvement in patients with idiopathic HES included small nodules with or without a halo of ground-glass attenuation and focal areas of ground-glass attenuation mainly in the lung periphery.
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Síndrome Hipereosinofílico/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Involvement of the lung in scleroderma is common, but pleural effusion and vasculitis are rarely reported in scleroderma. We describe a 43-year-old woman with limited scleroderma who developed an exudative pleural effusion associated with pleural leukocytoclastic vasculitis.
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Derrame Pleural/complicaciones , Esclerodermia Localizada/complicaciones , Vasculitis Leucocitoclástica Cutánea/complicaciones , Adulto , Femenino , Humanos , Derrame Pleural/patología , Esclerodermia Localizada/patología , Vasculitis Leucocitoclástica Cutánea/patologíaRESUMEN
Mucus hypersecretion contributes to the morbidity and mortality in acute asthma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophils is implicated in interleukin (IL)-13-induced mucin expression in GC. Treatment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-induced GC metaplasia dose dependently and completely. Instillation of IL-13 also induced tumor necrosis factor-alpha protein expression, mainly in infiltrating neutrophils. Control airway epithelium contained few leukocytes, but intratracheal instillation of IL-13 resulted in time-dependent leukocyte recruitment by IL-13-induced IL-8-like chemoattractant expression in airway epithelium. Pretreatment with an inhibitor of leukocytes in the bone marrow (cyclophosphamide) or with a blocking antibody to IL-8 prevented both IL-13-induced leukocyte recruitment and GC metaplasia. These findings indicate that EGFR signaling is involved in IL-13-induced mucin production. They suggest a potential therapeutic role for inhibitors of the EGFR cascade in the hypersecretion that occurs in acute asthma.
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Receptores ErbB/metabolismo , Interleucina-13/farmacología , Mucinas/biosíntesis , Activación Neutrófila/inmunología , Mucosa Respiratoria/metabolismo , Animales , Anticuerpos Bloqueadores/farmacología , Quimiotaxis de Leucocito/efectos de los fármacos , Quimiotaxis de Leucocito/inmunología , Ciclofosfamida/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Receptores ErbB/inmunología , Células Caliciformes/citología , Células Caliciformes/inmunología , Células Caliciformes/metabolismo , Inmunosupresores/farmacología , Interleucina-8/inmunología , Masculino , Metaplasia , Activación Neutrófila/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Ratas , Ratas Endogámicas F344 , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Organismos Libres de Patógenos Específicos , Células Th2/inmunología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Mucus hypersecretion from hyperplastic airway goblet cells is a hallmark of chronic obstructive pulmonary disease (COPD). Although cigarette smoking is thought to be involved in mucus hypersecretion in COPD, the mechanism by which cigarette smoke induces mucus overproduction is unknown. Here we show that activation of epidermal growth factor receptors (EGFR) is responsible for mucin production after inhalation of cigarette smoke in airways in vitro and in vivo. In the airway epithelial cell line NCI-H292, exposure to cigarette smoke upregulated the EGFR mRNA expression and induced activation of EGFR-specific tyrosine phosphorylation, resulting in upregulation of MUC5AC mRNA and protein production, effects that were inhibited completely by selective EGFR tyrosine kinase inhibitors (BIBX1522, AG-1478) and that were decreased by antioxidants. In vivo, cigarette smoke inhalation increased MUC5AC mRNA and goblet cell production in rat airways, effects that were prevented by pretreatment with BIBX1522. These effects may explain the goblet cell hyperplasia that occurs in COPD and may provide a novel strategy for therapy in airway hypersecretory diseases.