RESUMEN
Melkersson-Rosenthal syndrome (MRS) is an idiopathic, rare disorder manifested by facial swelling, congenital plicated tongue and recurrent peripheral facial nerve palsy. Labial involvement alone is referred to as cheilitis granulomatosa. Differential diagnosis of MRS includes allergic angioedema, bacterial, viral or filarial infections as well as autoimmunological inflammation in the course of systemic lupus erythematosus, dermatomyositis, and others. We present 4 patients who experienced periodically painless edema of the face and/or lips. Lesions were diagnosed as recurrent Quincke's edema and were treated with antihistamine agents and glucocorticoids without improvement. In all four cases of MRS, we were able to document impaired lymphatic drainage from the swollen area using lymphoscintigraphy. We also documented in follow-up lymphoscintigraphy a restoration of lymphatic flow in three of the four patients with MRS and these results corresponded with clinical improvement. We have demonstrated that lymphatic pathology plays an important role in pathophysiology of chronic facial swelling in patients with Melkersson-Rosenthal syndrome.
Asunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Síndrome de Melkersson-Rosenthal/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Drenaje , Femenino , Humanos , Linfedema/diagnóstico por imagen , Masculino , Síndrome de Melkersson-Rosenthal/terapia , Persona de Mediana Edad , CintigrafíaRESUMEN
Heparin and its derivatives exhibit a wide spectrum of biological functions affecting adhesion, activation and trafficking of leukocytes. The aim of that study was to investigate whether heparins are chemoattractants for neutrophils from peripheral blood of healthy volunteers and if chemotactic effects are identical in the same concentrations of unfractionated heparin and 3 low molecular weight heparin-nadroparin, enoxaparin and reviparin. We found that heparins are chemoatractants for neutrophils with potency comparable to fMLP known chemoatractant. Chemotaxis elucidated by identical doses by unfractionated heparin differed significantly from that after reviparin and enoxaparin.
Asunto(s)
Quimiotaxis/efectos de los fármacos , Fibrinolíticos/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , Heparina/análogos & derivados , Heparina/farmacología , Neutrófilos/efectos de los fármacos , Adulto , Femenino , Humanos , MasculinoRESUMEN
Bronchial asthma is a chronic condition with an inflammatory background--allergic inflammation. In recent years several observations have been published documenting activity of low molecular weight heparin (LMWH) in chronic inflammatory diseases of respiratory tract. This study was set up to evaluate the effect of nebulized LMWH on spirometric parameters and selected markers of allergic inflammation in bronchial asthma. Twenty patients diagnosed with mild or moderate asthma entered the study. At the beginning and at the end of the experiment every patient underwent bronchoscopy with BAL and in 15 of them bronchial biopsy was performed. Blood was drawn for ECP evaluation. LMWH was administered in nebulization in a dose 5000 U Xa/day for two weeks. BALf cellularity was evaluated as well as BALf IL-5 concentration. Further ELAM-1 and VCAM-1 expression in bronchial mucosa was examined in immunohistochemistry. We demonstrated that heparin treatment significantly enhanced FEV1 from 76.02 +/- 21.7% nominate value before to 92.4 +/- 21.8% after treatment (p < 0.005). Cellular profile of BALf changed, showing significant drop in percentages of eosinophils--from 7% to 6% (p < 0.05), macrophages--38 to 32% (p < 0.05) and neutrophils--32 to 28% (p < 0.05). Surprisingly we did not notice any change in ECP concentration in blood serum or IL-5 in BALf. Also adhesion molecules expression in bronchial mucosa remained unchanged. We conclude that chronic LMWH nebulization is a valuable treatment ameliorating asthmatic condition clearly due to anti-inflammatory properties of heparin. Both dose of LMWH used and the time of therapy have to be further investigated in order to develop treatment able to influence more of the elements of allergic inflammation.
Asunto(s)
Asma/complicaciones , Bronquitis/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/administración & dosificación , Administración por Inhalación , Adulto , Biopsia , Bronquios/patología , Bronquitis/complicaciones , Bronquitis/diagnóstico , Líquido del Lavado Bronquioalveolar/citología , Broncoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Pruebas de Función RespiratoriaRESUMEN
Interferon gamma (IFN-gamma) is considered one of the causative and intensifying factors in inflammation. The reaction to allergens releases IFN-gamma, an immunomodulatory cytokine known to inhibit IgE synthesis and Th cell proliferation. The aim of the study was to evaluate the influence of IFN-gamma on leukotriene (LT) release in vitro, from human leukocytes of atopic patients with pollinosis and asthma. Thirty-eight patients were enrolled in the study: 15 with pollinosis and 23 asthmatics. In the presence of IL-3, leukocytes were stimulated with specific allergens. Other samples of leukocytes were preincubated with different concentrations of IFN-gamma for 15 min before allergen stimulation. The concentration of LT in supernatants was measured according to the CAST-ELISA procedure. We stated that IFN-gamma had significantly diminished LT release in a dose-dependent mode from the leukocytes of pollinotics. IFN-gamma did not change LT release in the asthmatic group, although, in leukocytes the small and medium basic production of LT, IFN-gamma caused a statistically significant fall in LT generation.
Asunto(s)
Asma/inmunología , Inmunoglobulina E/inmunología , Interferón gamma/farmacología , Leucocitos/efectos de los fármacos , Leucotrienos/metabolismo , Rinitis Alérgica Estacional/inmunología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Evidence has now accumulated that heparin can significantly affect immune response including allergic inflammation. Cell motility is supposed to be very crucial in this process. Thus the aim of our study was to investigate whether heparin is a chemoattractant for some inflammatory cells and is also capable of influencing chemotaxis induced by typical chemoattractants. Peripheral blood mononuclear cells (PBMCs) and neutrophils from 10 healthy subjects were obtained by gradient centrifugation. Chemotaxis assays towards either heparin (molecular weight 16 kDa) or low molecular weight heparin--fraxiparine (molecular weight 5 kDa) were performed in Boyden chambers. We found that both heparin molecules are chemoattractants for both PBMCs and neutrophils in the wide concentration range (0.1-2000 microg/ml). However, maximal chemotaxis was observed at concentrations 50-100 microg/ml (fraxiparine) and 1-50 microg/ml (heparin). We also found that fraxiparine was able to significantly increase chemokinesis and decrease chemotaxis in the gradient of both fMLP and IL-8. These results indicate that heparin is a potent regulator of cell migration.
Asunto(s)
Anticoagulantes/farmacología , Movimiento Celular/efectos de los fármacos , Factores Quimiotácticos/farmacología , Heparina/farmacología , Leucocitos Mononucleares/citología , Neutrófilos/citología , Adulto , Movimiento Celular/inmunología , Quimiotaxis de Leucocito/efectos de los fármacos , Humanos , Interleucina-8/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , N-Formilmetionina Leucil-Fenilalanina/farmacología , Nadroparina/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunologíaRESUMEN
Evidence has now accumulated that heparin can significantly affect immune response including allergic inflammation. Cell migration is supposed to be very crucial in this process. Thus the aim of that study was to investigate whether low molecular weight heparin-nadroparine is chemoattractant for some inflammatory cells in asthmatics. Peripheral blood mononuclear cells (PBMC) and neutrophils from 15 asthmatics were obtained by gradient centrifugation. Chemotaxis was compared with that induced with known chemoattractants-fMLP and IL-8. We found that nadroparine caused significant and dose dependent chemotaxis of PBMC and comparable with influence of fMLP and IL-8. Nadroparine amplified chemotaxis of neutrophils but not significantly. Chemotaxis induced by fMLP and IL-8 was diminished when blood cells were incubated earlier with 50 mg of nadroparine.
Asunto(s)
Asma , Quimiotaxis/efectos de los fármacos , Fibrinolíticos/farmacocinética , Heparina de Bajo-Peso-Molecular/farmacocinética , Leucocitos Mononucleares/metabolismo , Nadroparina/farmacocinética , Neutrófilos/metabolismo , Adulto , Anciano , Asma/tratamiento farmacológico , Asma/inmunología , Femenino , Fibrinolíticos/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Nadroparina/uso terapéuticoRESUMEN
The rats exposition for 15 weeks to SO2 inhalation resulted in chronic bronchitis. The BALF evaluation revealed an increase in inflammatory cells number: neutrophils, macrophages, lymphocytes. Electron microscope examination demonstrated that macrophages were activated in comparison to healthy rats. Immunoreactive endothelin was found in bronchial specimens mainly in alveolar macrophages (we used a computer-assisted system of image analysis). The expression of endothelin was significantly increased in rats irritated with SO2. Low molecular weight heparin-nadroparine has been administered parenterally in 3 doses to 3 groups of rats. In animals subjected to SO2 irritation and simultaneous heparin treatment we observed significant decrease in number and activation of macrophages and endothelin expression as well. The results of this experiment suggest antiinflammatory properties of heparin.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Bronquitis/metabolismo , Endotelinas/metabolismo , Fibrinolíticos/farmacología , Heparina/farmacología , Macrófagos Alveolares/efectos de los fármacos , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , RatasRESUMEN
Evidence has now accumulated that heparin can significantly affect immune response including allergic inflammation. Cell motility is supposed to be very crucial in this process. Thus the aim of that study was to investigate whether heparin is chemoattractant for some inflammatory cells in asthmatics. Peripheral blood mononuclear cells and neutrophils from 6 healthy subjects and 16 asthmatics were obtained by gradient centrifugation. Chemotaxis assays towards low molecular weight heparin-Clexane were performed in Boyden chambers. We found that heparin is chemoattractant for both PBMCs and neutrophils in the wide concentration range (1-2000 micrograms/ml)--maximal chemotaxis was observed at concentrations 50-500 micrograms/ml. Chemotactic motility of cells from asthmatics was weaker than from healthy subjects; the difference wasn't significant.
Asunto(s)
Asma/sangre , Quimiotaxis de Leucocito/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Adulto , Anciano , Asma/inmunología , Humanos , Leucocitos/efectos de los fármacos , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Valores de ReferenciaRESUMEN
Bronchitis was evoked in 20 rats by SO2 inhalation. Ten rats were exposed to SO2 only, 10 others were exposed to SO2 and treated with heparin simultaneously. The control group consisted of other 10 rats. NO concentration in the air exhaled by all animals was determined. The experiment was carried out in a specially constructed chamber. It lasted 15 weeks. In the group of animals exposed to SO2 only, NO concentration was found beginning from the %th week, with the maximum concentration in the 10th week. In the group of animals exposed to SO2 and treated with heparin NO concentration was much lower than in the above group. NO was not found in the control group. The conclusion is that NO concentration in the exhaled air is a result of bronchial inflammation, and can be decreased during treatment with heparin.
Asunto(s)
Pruebas Respiratorias , Bronquitis/diagnóstico , Óxido Nítrico/análisis , Animales , Biomarcadores , Bronquitis/inducido químicamente , Bronquitis/tratamiento farmacológico , Heparina/farmacología , Heparina/uso terapéutico , Masculino , Ratas , Valores de Referencia , Dióxido de AzufreRESUMEN
The aim of this study was to investigate the effect of heparin on the rat bronchial mucosa changes induced by sulphur dioxide (SO2) inhalation. Sixty five rats were used in this experiment. Five of them constituted a control group, while 60 were exposed to SO2. Forty of the latter subgroup were additionally treated with low molecular weight heparin (LMWH), either during or after terminating exposure to SO2. In all animals exposed to SO2 inflammatory cells were found in broncho-alveolar lavage fluid (BALf) in numbers significantly higher from those observed in healthy controls. The rats exposed to SO2 and treated with LMWH showed intermediate cell pattern in the bronchi between healthy and SO2- exposed animals. When comparing histological picture of the bronchi, we noted extensive changes in irritated rats. These changes were either less expressed or totally absent in animals treated with heparin. The activity of enzymes: acid phosphatase (ACP), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) rose in BALf, although the rise was not parallel and did not correlate with the magnitude of cellular influx or histological changes. Heparin did not influence this changes.
Asunto(s)
Bronquitis/tratamiento farmacológico , Heparina/uso terapéutico , Fosfatasa Ácida/análisis , Animales , Bronquios/efectos de los fármacos , Bronquios/patología , Bronquitis/inducido químicamente , Bronquitis/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , L-Lactato Deshidrogenasa/análisis , Masculino , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Tiempo de Tromboplastina Parcial , Ratas , Dióxido de Azufre/toxicidadRESUMEN
In 20 rats bronchitis was evoked by permanent 12-week long inhalation of SO2. For this purpose a special chamber with gas supply was prepared. In all rats exposed to SO2 changes in cellularity of BALF were found (a statistically significant increase of the percent of macrophages and neutrophils). Histologic examination revealed bronchial changes especially in epithelium. The method applied, based on an original technology is cheap and effective and can be recommended in developing experimental bronchitis.
Asunto(s)
Bronquitis/patología , Líquido del Lavado Bronquioalveolar/citología , Pulmón/patología , Animales , Bronquitis/inducido químicamente , Enfermedad Crónica , Epitelio/patología , Fibrosis , Masculino , Metaplasia , Ratas , Dióxido de AzufreRESUMEN
UNLABELLED: The aim of our study was to evaluate the influence of heparin on inflammed bronchial mucosa in rats. Sixty five animals were used in the study; 5 of them constituted the control group, whereas 60 were submitted to long term SO2 irritation in specially constructed chamber, what resulted in chronic bronchitis. Low molecular weight heparin preparation--Frexiparine has been administered in inhalation or parenterally to 40 rats, simultaneously or immediately after SO2 exposition. In all animals exposed to SO2 the BALF evaluation revealed predomination of inflammatory cells. The results obtained in healthy rats were different and BALF cellular sediment contained 92% of epithelial cells. However in animals submitted to SO2 irritation and simultaneous heparin treatment we observed significant increase of the number of inflammatory cells in BALF in comparison to healthy rats but it was not as high when compared to animals irritated only with SO2. In all animals exposed only to SO2 we were able to find disseminate inflammatory changes and/or planoepithelial metaplasia in bronchial specimens. However we did not observe any sings of inflammation in specimens obtained from 50% of heparin treated rats, whereas in the other 50% they were described as mild or moderate. CONCLUSIONS: 1. Low molecular weight heparin decreased signs of experimentally provoked bronchial inflammation in rats. 2. Simultaneous heparin and SO2 administration was extremely efficient. This finding suggests prophylactic properties of heparin. 3. The heparin activity does not depend on inhalatory or parenteral way of administration.
Asunto(s)
Bronquitis/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar/citología , Fibrinolíticos/administración & dosificación , Pulmón/efectos de los fármacos , Nadroparina/administración & dosificación , Administración por Inhalación , Animales , Bronquitis/inducido químicamente , Infusiones Parenterales , Pulmón/patología , Masculino , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Ratas , Dióxido de AzufreRESUMEN
In this review we try to summarize some of the new informations about the genetic base of bronchial asthma. We also mention apoptosis (programmed cell death) as the process modulating cell proliferation, differentiation and death. According to the latest reports, the disorders of the regulation of apoptosis may play an important role an the pathogenesis of autoimmune and atopic diseases (including bronchial asthma), AIDS and neoplastic diseases. There is a linkage between the induction of apoptosis and signal transduction disorders. We describe the Raf/MECK/ERK/MAP signal transduction pathway and 14-3-3 protein--the peptide which possibly might participate in the initiation of the programmed cell death.
Asunto(s)
Apoptosis , Hipersensibilidad Inmediata/fisiopatología , Proteína Quinasa C/antagonistas & inhibidores , Proteínas/metabolismo , Tirosina 3-Monooxigenasa , Proteínas 14-3-3 , Cromosomas Humanos Par 5 , Citocinas/fisiología , Antígenos HLA/genética , Humanos , Interleucinas/genética , Sistemas Neurosecretores/fisiopatología , Transducción de SeñalAsunto(s)
Asma/tratamiento farmacológico , Heparina/uso terapéutico , Animales , Asma/metabolismo , Broncoconstricción/efectos de los fármacos , Broncoconstricción/fisiología , Células Cultivadas , Heparina/farmacología , Humanos , Receptores Muscarínicos/efectos de los fármacos , Receptores Muscarínicos/metabolismoRESUMEN
Heparine is used as a therapeutic anticoagulant. Research carried out in the last years showed in both in vivo and in vitro experiments (also in men), that this is a pleiotropic substance with many diverse activities. Immunoregulatory properties of heparine, including immunosuppressive and most of all anti-proliferative lead to create the theory of its possible use in several chronic inflammatory processes. First experiments seem to justify this opinion.
Asunto(s)
Antiinflamatorios/farmacología , Heparina/farmacología , Animales , Antiinflamatorios/uso terapéutico , Células Cultivadas/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Heparina/uso terapéutico , Humanos , Hipersensibilidad Tardía/tratamiento farmacológico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Linfocitos/efectos de los fármacos , Mastocitos/efectos de los fármacosRESUMEN
15 patients with mild bronchial asthma were selected for study. They inhaled salbutamol 2.5 mg three times daily for 8 days. Bronchodilator dose-response studies were performed by administering increasing doses of isuprel intravenously before and after treatment with salbutamol. Histamine provocation was done to estimate airway responsiveness. That was performed prior to and after salbutamol therapy. Regular inhaled salbutamol increased airway responsiveness to histamine--Pc20 was significantly reduced from 1.95 mg/ml--before treatment to 0.44 mg/ml--after salbutamol therapy. The bronchodilatory effect after isuprel was the same before and after treatment with salbutamol.
Asunto(s)
Albuterol/administración & dosificación , Asma/tratamiento farmacológico , Administración por Inhalación , Adulto , Pruebas de Provocación Bronquial , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravenosas , Isoproterenol/administración & dosificación , Masculino , Ventilación Pulmonar/efectos de los fármacos , EspirometríaRESUMEN
Authors compared efficacy of high Atrovent doses and Salbutamol on pulmonary ventilation. Examinations were performed in 20 patients with BA and 20 patients with COPD. Each drug was given on separate days in increasing doses (0.04; 0.25 and 0.5 mg) of Atrovent and 0.2 mg of Salbutamol. Bronchodilatation was assessed by measurement of FEV1; FEF25%, FEF50%, FEF75%. Maximal effect in patients with COPD was reached with doses of 0.25 and 0.5 mg of Atrovent (delta FEV1(%) +22). Salbutamol and 0.04 mg of Atrovent were significantly less effective. In patients with BA Salbutamol (delta FEV1(%) +49) are likely to be more effective bronchodilator an Atrovent (delta FEV1(%) +26).