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Autocatalytic reaction fronts between two reacting species in the absence of fluid flow, propagate as solitary waves. The coupling between autocatalytic reaction front and forced simple hydrodynamic flows leads to stationary fronts whose velocity and shape depend on the underlying flow field. We address the issue of the chemico-hydrodynamic coupling between forced advection in porous media and self-sustained chemical waves. Towards that purpose, we perform experiments over a wide range of flow velocities with the well characterized iodate arsenious acid and chlorite-tetrathionate autocatalytic reactions in transparent packed beads porous media. The characteristics of these porous media such as their porosity, tortuosity, and hydrodynamics dispersion are determined. In a pack of beads, the characteristic pore size and the velocity field correlation length are of the order of the bead size. In order to address these two length scales separately, we perform lattice Boltzmann numerical simulations in a stochastic porous medium, which takes into account the log-normal permeability distribution and the spatial correlation of the permeability field. In both experiments and numerical simulations, we observe stationary fronts propagating at a constant velocity with an almost constant front width. Experiments without flow in packed bead porous media with different bead sizes show that the front propagation depends on the tortuous nature of diffusion in the pore space. We observe microscopic effects when the pores are of the size of the chemical front width. We address both supportive co-current and adverse flows with respect to the direction of propagation of the chemical reaction. For supportive flows, experiments and simulations allow observation of two flow regimes. For adverse flow, we observe upstream and downstream front motion as well as static front behaviors over a wide range of flow rates. In order to understand better these observed static state fronts, flow experiments around a single obstacle were used to delineate the range of steady state behavior. A model using the "eikonal thin front limit" explains the observed steady states.
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We report on numerical studies of avalanches of an autocatalytic reaction front in a porous medium. The front propagation is controlled by an adverse flow resulting in upstream, static, or downstream regimes. In an earlier study focusing on front shape, we identified three different universality classes associated with this system by following the front dynamics experimentally and numerically. Here, using numerical simulations in the vicinity of the second-order transition, we identify an avalanche dynamics characterized by power-law distributions of avalanche sizes, durations, and lateral extensions. The related exponents agree well with the quenched-Kardar-Parisi-Zhang theory, which describes the front dynamics. However, the geometry of the propagating front differs slightly from that of the theoretical one. We show that this discrepancy can be understood in terms of the nonquasistatic correction induced by the finite front velocity.
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The secretory immunoglobulin A (IgA) system plays an important role in the protection of epithelial surfaces. The aim of this study was to evaluate whether the measurement of the primary airway Ig (sIgA) concentration in bronchial washings is clinically useful in patients with airway epithelial injury or inflammation. We measured serum IgA levels and sIgA concentrations in the bronchial lavages of patients with chronic bronchitis (n = 10), bronchiectasis (n = 15), lung cancer (n = 15) and in healthy control subjects (n = 10). Absolute sIgA levels of bronchial lavage fluids in the chronic bronchitis, bronchiectasis and lung cancer groups were higher than the controls, but there was no significant difference between the groups. sIgA/ml recovered bronchial fluid ratios were similar in the all groups. Standardisation of samples by means of albumin concentration ratios (sIgA/alb) showed that the bronchial lavages of the patients with lung cancer, chronic bronchitis and bronchiectasis were generally similar and demonstrated a significantly decreased sIgA/alb ratio compared to that of control subjects (p = 0.001, p < 0.05 and p < 0.05). sIgA/alb ratios in bronchial lavages recovered from involved lung of the patients with lung cancer and bronchiectasis were lower as compared to uninvolved lung (p < 0.001 and p < 0.05). There was no significant difference in serum IgA levels between all groups. As a result, although our findings seem partly to confirm the hypothesis that local bronchial IgA secretion is impaired in areas of bronchial epithelial injury or inflammation, we thought that sIgA would be useless as a marker of respiratory epithelial injury or inflammation in patients with chronic bronchitis, bronchiectasis and lung cancer.
Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Inmunoglobulina A Secretora/análisis , Inmunoglobulina A/sangre , Enfermedades Respiratorias/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Albúmina Sérica/análisisRESUMEN
OBJECTIVE: This study investigates the deleterious effects of corticosteroids on tracheal anastomotic healing and the ability of vitamin A to reverse these effects in a rat model. METHODS: Forty-two adult Wistar rats were randomly divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I, sham (N=6); Group II, control (N=6); Group III, dexamethasone, 0.1 mg/kg/day intramuscularly (N=10); Group IV, dexamethasone 0.1 mg/kg/day intramuscularly+vitamin A 10000 IU/kg/day by gavages (N=10); and Group V, vitamin A 10000 IU/kg/day by gavages for a week (N=10). After 7 days, anastomotic healing was assessed by measurement of bursting pressure, hydroxyproline content and subsequent histological grading using the modified Ehrlich/Hunt scale. RESULTS: Bursting pressures and hydroxyproline contents were as follows: Group I: 977+/-8 mmHg and 11.80+/-0.3 microg/mg (mean+/-standard error of the mean); Group II: 890+/-55 mmHg and 9.93+/-0.6 microg/mg; Group III: 555+/-26 mmHg and 11.90+/-1.3 microg/mg; Group IV: 873+/-73 mmHg and 10.24+/-2.2 microg/mg; Group V: 905+/-45 mmHg and 7.51+/-0.8 microg/mg, respectively. Bursting pressure of Group III was found to be significantly lower when compared to other groups (P<0.0001). However, statistical significance was not found among the study groups for the hydroxyproline content. Except for inflammatory cell infiltration, histological parameters including epithelial regeneration, fibroblast proliferation, collagen content, and angiogenesis demonstrated significant differences among the groups. CONCLUSION: The present study demonstrates that dexamethasone significantly impairs the healing of tracheal anastomoses in rats and postoperative administration of vitamin A appreciably reverses this inhibitory effect. Patients receiving corticosteroids may benefit from vitamin A when undergoing prolonged intubation and laryngotracheal reconstruction.
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Dexametasona/farmacología , Tráquea/patología , Tráquea/cirugía , Vitamina A/farmacología , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Anastomosis Quirúrgica/métodos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Inmunohistoquímica , Inyecciones Intramusculares , Masculino , Probabilidad , Distribución Aleatoria , Ratas , Ratas Wistar , Valores de Referencia , Sensibilidad y Especificidad , Resistencia a la TracciónRESUMEN
Peripheral nervous system disorders in COPD (chronic obstructive pulmonary disease) have been found more frequently than usual neurologic practice. We planned this prospective clinical and electrophysiological study to determine the incidence and characteristics of neuropathy in patients with COPD. We studied 49 patients with COPD in whom other causes of polyneuropathy had been excluded. COPD patients were divided into two groups: 21 hypoxemic and 28 normoxemic. Age and sex matched, nonsmoker, 21 healthy subjects were included as the control group. We investigated the results of clinical (neurological symptom score-NSS, neurological disability score-NDS and vibration perception thresholds- VPT) and neurophysiological evaluations in COPD patients and the control group. A value over the mean +/- 2.5 SD of control group were accepted pathologic. NSS results were pathologic in 34% of COPD patients, NDS in 42% and VPT in 94%. Carpal tunnel syndrome was found in 24% of the patients, neuropathy in 55%, and polyneuropathy in 44.8%. In conclusion, the incidence of neuropathy was more than expected, the rate of axonal neuropathy was significantly higher in the hypoxemic group than normoxemic group and the severity of neuropathy was correlated with the degree of hypoxemia.
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Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Síndrome del Túnel Carpiano/diagnóstico , Síndrome del Túnel Carpiano/fisiopatología , Electrodiagnóstico , Femenino , Humanos , Hipoxia/diagnóstico , Hipoxia/fisiopatología , Isquemia/diagnóstico , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Examen Neurológico , Nervios Periféricos/irrigación sanguínea , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Umbral Sensorial/fisiologíaRESUMEN
Compliance is often poor in patients receiving long-term oxygen therapy (LTOT). We assessed some characteristics of LTOT patients and factors associated with non-effective use of LTOT in Turkey. A questionnaire was sent to 1100 patients who purchased their oxygen equipment between January 1995 and September 1999 from the largest oxygen company in Turkey. The questionnaire included items about daily duration of oxygen therapy, home situation, lifestyle, education level of the patient, smoking habits and side effects of oxygen therapy. In addition, patients were asked whether supplementary medical and technical education on oxygen therapy was explained to them. 379 patients responded. The patients had been receiving LTOT for 24.3 +/- 13 months. The mean duration of oxygen therapy was 9 +/- 6.8 hours/day. Only 28.2% of the patients managed to receive oxygen therapy for 15 h or more daily. 33.2% of the patients were told to use oxygen only when they had difficulty in breathing. 6.9% of the patients continued to smoke and 8.7% of the patients had complaints related to oxygen therapy. Logistic regression analysis identified that the likelihood of achieving effective oxygen therapy increased 4.5 fold (p < 0.001) when the physician gave pre-treatment education to the patient about the therapy, and effective use increased 3.8 fold (p < 0.002) when the patients were closely followed-up by the physician. We conclude that pre-treatment education of the patient about the therapy and close follow-up by the physician may increase the compliance rate to LTOT.
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Enfermedades Pulmonares Obstructivas/epidemiología , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Anciano , Femenino , Humanos , Cuidados a Largo Plazo/estadística & datos numéricos , Enfermedades Pulmonares Obstructivas/rehabilitación , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Autocuidado/estadística & datos numéricos , TurquíaRESUMEN
The aim of the present study was to investigate the electrophysiology of the phrenic nerve and the diaphragm muscle during sepsis. In total, 26 rats underwent either sham laparotomy or caecal ligation and puncture (CLP). Electrophysiology was evaluated via a phrenic nerve conduction study and needle electromyography of the diaphragm, prior to CLP, 6 and 24 h post-CLP and on day 7. The histopathology of the diaphragm muscle and phrenic nerve was also examined on day 7. In the sepsis group, the phrenic nerve conduction study showed decreased amplitude of compound action potential (CMAP), and prolongation in the duration and the latency of CMAP. The diaphragmatic needle electromyography showed decreased amplitude and frequency of the motor unit action potential (MUP), and prolongation in the duration of MUP, at all time points, compared with the pre-CLP values. The electrophysiological abnormalities were consistent with axonal and demyelinating phrenic nerve neuropathy. Electrophysiological abnormalities were present at 6 h with worsening at 24 h and on day 7. Histopathological examination showed normal muscular fibres and focally slight myelin degenerations of the phrenic nerve fibres. In conclusion, sepsis induced phrenic nerve neuropathy as early as the 6th h in rats.
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Enfermedades del Sistema Nervioso Periférico/etiología , Nervio Frénico/fisiopatología , Parálisis Respiratoria/fisiopatología , Sepsis/complicaciones , Animales , Modelos Animales de Enfermedad , Electrodiagnóstico , Ratas , Ratas Wistar , Parálisis Respiratoria/etiologíaRESUMEN
The present study evaluated the possible effects of exposure to polypropylene flock on respiratory health and serum cytokines in a cross-sectional study of workers from a plant in Turkey. A total of 50 polypropylene flocking workers were compared to a control group of 45 subjects. All subjects filled out a respiratory questionnaire and underwent a physical examination, a chest radiograph and pulmonary function testing, including single breath carbon monoxide diffusing capacity (DL,CO). Serum interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured. Additionally, high resolution computed tomography (HRCT) of the chest was performed in 10 exposed workers with low DL,CO. Work-related respiratory symptoms were reported in 26% of the exposed subjects and in 13.3% of the controls. Logistic regression analysis showed that the risk of respiratory symptoms increased 3.6 fold in polypropylene flocking workers when compared to controls. Parameters of the study group, including per cent predicted: forced vital capacity, forced expiratory volume in one second, forced mid-expiratory flow 25-75% and DL,CO, were significantly lower than in controls. Multivariate analyses showed that being a polypropylene flocking worker was a predictive factor for impairment of pulmonary function. Serum IL-8 and TNF-alpha levels were increased in the study group compared with the controls. HRCT revealed peribronchial thickening and diffuse ground glass attenuation in some subjects. The present study suggests the presence of subtle or the beginning of interstitial lung disease in these polypropylene flocking workers.
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Contaminantes Ocupacionales del Aire/efectos adversos , Industria Química , Salud Laboral , Polipropilenos/efectos adversos , Fibrosis Pulmonar/inducido químicamente , Adulto , Factores de Edad , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Exposición Profesional/efectos adversos , Prevalencia , Probabilidad , Fibrosis Pulmonar/epidemiología , Valores de Referencia , Pruebas de Función Respiratoria , Medición de Riesgo , Factores Sexuales , Turquía/epidemiologíaRESUMEN
OBJECTIVE: The aim of the study was to investigate the abnormalities of brainstem auditory evoked potentials (BAEP) in patients with severe chronic obstructive pulmonary disease (COPD). METHODOLOGY: Twenty-one patients with severe COPD (16 men, five women; mean age: 64 +/- 6.5 years), in whom other causes of BAEP abnormalities had been excluded, were studied. Age-matched, non-smoking, healthy subjects acted as a control group. We performed pulmonary function tests, arterial blood gas analysis and bilateral BAEP measurements in COPD patients and control groups. RESULTS: Brainstem auditory evoked potentials were abnormal in 16 (76.1%) of the 21 COPD patients. Most prominent BAEP abnormalities were prolonged wave I peak latencies (42.8%), V wave peak latencies (38.1%), and III-V interpeak latencies (IPL) (38.1%). In five patients, a prolonged central transmission time (I-V IPL) was observed. No significant correlation was evident between the BAEP parameters and pH, PaO2, PaCO2, FEV1%, FEV1/FVC, haematocrit, duration of disease or cigarette consumption. CONCLUSION: The functions of the eighth cranial nerve and brainstem were highly impaired in severe COPD. These pathological BAEP alterations in severe COPD might be due to the chronic hypoxic-hypercapnic status occurring in the brainstem.
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Potenciales Evocados Auditivos del Tronco Encefálico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Estudios Transversales , Femenino , Humanos , Hipercapnia/fisiopatología , Hipoxia/fisiopatología , Masculino , Persona de Mediana Edad , Policitemia/fisiopatología , EspirometríaRESUMEN
Bronchoscopy has the potential to propagate infections. Bacterial translocation was hypothesised to be the cause of infections observed following bronchoscopy and this study was designed to assess the risk of bacterial translocation following rigid bronchoscopy in rats. A total of 30 rats were evaluated. The study group (n=15) underwent rigid bronchoscopy. Arterial blood gas analysis was performed in all rats. Blood and tissue cultures from the ileum, caecum, mesenteric lymph nodes, liver, spleen, mediastinal lymph nodes and lung were obtained 24 h following bronchoscopy. Bacterial translocation to the mesenteric lymph nodes was found in seven of 15 rats (46.7%) that underwent bronchoscopy, compared with none of the controls. Of the seven positives, three rats (42.8%) also demonstrated other organ involvement, such as the liver and spleen. Escherichia coli, Salmonella typhymirium, S. enteritidis and Pseudomonas spp. were found as translocating bacteria. In the study group, pH and arterial oxygen tension were significantly lower and arterial carbon dioxide tension was higher, compared with controls. This study shows that rigid bronchoscopy may induce bacterial translocation in rats. Further investigations aimed at understanding the clinical consequences of this phenomenon are warranted.
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Traslocación Bacteriana/fisiología , Broncoscopía/efectos adversos , Animales , Bacteriemia/etiología , Ratas , Ratas Wistar , RiesgoRESUMEN
BACKGROUND: Changes in bronchial osmolarity is a well-known factor for bronchoconstricion. Recenty, nonisotonic aerosols have begun to be used for the assessment of bronchial hyperreactivity. Hypertonic KCl can cause bronchoconstriction even in non-symptomatic asthmatic patients. OBJECTIVE: To evaluate the protective role of heparin on hypertonic KCl-induced bronchospasm in asthma. METHODS: Thirty-eight asthmatic patients were included in this double-blind, placebo-controlled study. On day 1 of the study, after performing the respiratory function test (RFT), patients had inhaled KCl 10% and RFTs were done after 20 minutes. On day 2 of the study, after the basal RFT, 18 patents inhaled NaCl 0.9% 0.2 mLkg solution. After the completion of this procedure, patients waited for 20 minutes and inhaled KCl 10% 10 mL, and RFTs were repeated 20 minutes later. The second group consisted of 20patients who inhaled heparn 1,000 units/kg after the RFTs were performed. Twenty minutes later, they inhaled KCl 10% and waited for 20 minutes. Finally, RFTs were done and compared with those from the other group. RESULTS: In the control group, forced expiratory volume in one second (FEV1) decreased 17.4% on day 1 and 16.4% on day 2. In the heparin-treated group, FEV1 decreased 18.6% on day 1, but almost no change occurred after this group was treated with heparin before inhalation of hypertonic KCl on day 2. CONCLUSIONS: Heparin was found to be highly protective against hypertonic KCl induced bronchospasm in bronchial asthma.
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Espasmo Bronquial/prevención & control , Heparina/uso terapéutico , Cloruro de Potasio/efectos adversos , Adolescente , Adulto , Asma/prevención & control , Espasmo Bronquial/inducido químicamente , Método Doble Ciego , Femenino , Humanos , Soluciones Hipotónicas , Masculino , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: This study aimed to investigate whether exposure to sunflower pollen (Helianthus annuus) increases both sensitization and respiratory symptoms, and whether or not it affects lung functions in sunflower processing workers. METHODS: The largest sunflower processing factories in the Thrace region of Turkey participated in this study. Workers from the units directly exposed to sunflower seed enrolled as the study group (n = 102) and workers who were not directly exposed to Helianthus annuus pollen (n = 102) were the control group. Detailed questionnaires covering respiratory and allergic symptoms were completed, and skin prick tests and lung function tests were performed. RESULTS: We found a very high rate (23.5%) of sensitization to Helianthus annuus in the study group compared to the controls (P<0.001). Logistic regression analysis showed that the risk of sensitization to H. annuus was increased 4.7-fold (odds ratio = 4.17, 95%) confidence interval = 1.3-16.7) if subjects were exposed to sunflower pollen in the workplace. While asthmatic symptoms and allergic skin diseases were not different between the two groups, workers in the study group had a higher rate of allergic rhinitis and conjunctivitis (P<0.05). We found that pulmonary function was significantly impaired in the study group (P<0.01). Using a multivariate analysis model, inclusion in the study group was found to be a predictive factor for impairment of lung function (P=0.002). CONCLUSIONS: We conclude that sunflower pollen has high allergenic potential, especially when there is close contact, and exposure to sunflower pollen in the workplace can result in impairment in lung function.
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Enfermedades de los Trabajadores Agrícolas/inmunología , Conjuntivitis Alérgica/inmunología , Helianthus/inmunología , Polen/inmunología , Hipersensibilidad Respiratoria/inmunología , Rinitis/inmunología , Enfermedades de los Trabajadores Agrícolas/fisiopatología , Alérgenos/inmunología , Conjuntivitis Alérgica/fisiopatología , Estudios Transversales , Humanos , Análisis Multivariante , Exposición Profesional , Pruebas de Función Respiratoria , Hipersensibilidad Respiratoria/fisiopatología , Rinitis/fisiopatología , Pruebas Cutáneas , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study aimed to investigate the rate of occupational sensitization to horse hair in grooms and whether occupational exposure to horse hair increases respiratory and allergic symptoms and affects lung function in grooms or not. METHODS: This is a cross-sectional study. Two hundred grooms were randomly selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One hundred and twenty-five subjects agreed to enter the study. Ninety-two workers who worked in the different parts of this hippodrome enrolled as the control group. A detailed questionnaire including respiratory and allergic symptoms was filled in, physical examination, skin prick tests and pulmonary function tests were performed. RESULTS: Sensitization to horse hair was 12.8% in grooms and 4.3% in controls. The difference was statistically significant (P = 0.0035). Asthma was found in 14.4% of the grooms and 5.4% of the controls, allergic rhinitis in 42.4% of the grooms and 18.4% of the controls, allergic conjunctivitis in 35.2% of the grooms and 15.2% of the controls, and allergic skin diseases in 32.8% of the grooms and 13% of the controls. The differences were statistically significant (P = 0.043, P = 0.0002, P = 0.001 and P = 0.0008, respectively). The means of FEV1, FEV1/FVC and FVC parameters were significantly lower in the groom group (P = 0.006, P = 0.001 and P = 0.003, respectively). In the multivariate analysis, being in the groom group and working years were found to be predictive factors for impairments of lung function (P < 0.001 and P = 0.002, respectively). CONCLUSION: Occupational exposure to horse increases the sensitization to horse hair, induces asthma and allergic symptoms and also impairs lung functions.
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Contaminantes Ocupacionales del Aire/efectos adversos , Alérgenos/efectos adversos , Crianza de Animales Domésticos , Caballos , Hipersensibilidad/inmunología , Enfermedades Profesionales/inmunología , Adolescente , Adulto , Anciano , Animales , Asma/inmunología , Asma/fisiopatología , Estudios de Casos y Controles , Conjuntivitis Alérgica/inmunología , Conjuntivitis Alérgica/fisiopatología , Estudios Transversales , Dermatitis Alérgica por Contacto/inmunología , Dermatitis Alérgica por Contacto/fisiopatología , Cabello/inmunología , Humanos , Hipersensibilidad/fisiopatología , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedades Profesionales/fisiopatología , Pruebas de Función Respiratoria , Rinitis Alérgica Perenne/inmunología , Rinitis Alérgica Perenne/fisiopatología , Factores de TiempoRESUMEN
OBJECTIVE: Scientific evidence of functional interface between the immune and sensory motor systems of the gut and respiratory systems has been reported. In recent studies excess prevalence of bronchial hyper-responsiveness has been shown among patients with irritable bowel syndrome (IBS). The purpose of our study was to investigate the possible relationship between IBS and asthma. METHODS: One hundred thirty-three patients with IBS (108 women, 25 men) and 137 control subjects (105 women, 32 men) were included in this study. Both for IBS and the control group, the mean ages were 41.64+/-9.45 yr and 39.94+/-10.62 yr, respectively. Patients more than 50 yr old, with any organic GI disease, acute respiratory system infection, current or ex-smokers, and patients using drugs affecting smooth muscle and autonomic nervous system were not included in the study. Respiratory symptoms were questioned and pulmonary function tests were performed for every subject. RESULTS: There were 45 (33.8%) and eight (5.8%) subjects with respiratory symptoms in IBS and control groups, respectively (p < 0.0001). Twenty-one (15.8%) patients from the IBS group and two (1.45%) patients from the control group had the diagnosis of asthma according to history, clinical, and PFT findings. There was no statistical difference between two groups with respect to percentage of forced vital capacity and forced expiratory volume in 1 s-to-forced vital capacity. The difference between the two groups in forced expiratory volume in 1 s, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate was statistically significant (p < 0.01). CONCLUSION: We found that the prevalence of asthma was more common in the IBS group than in controls. Our finding supports the speculation that asthma and IBS may share common pathophysiological processes.
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Asma/complicaciones , Enfermedades Funcionales del Colon/complicaciones , Enfermedades Funcionales del Colon/fisiopatología , Pulmón/fisiopatología , Adulto , Asma/epidemiología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Flujo Espiratorio Medio Máximo , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Prevalencia , Valores de Referencia , Capacidad VitalRESUMEN
Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.