RESUMEN
In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The global concentration in serum or bronchiolar lavage fluid A1PI including active and inactivated A1PI was measured immunologically by rate nephelometry and radial immunodiffusion. The functional activity of A1PI, expressed as free inhibitor activity against trypsin and leukocyte elastase, confirmed that the infused A1PI remained mostly in its active form in the circulation. Reported adverse reactions were moderate and did not require alteration to the schedule of the infusions and/or the dose and rate of administration. Antibodies to A1PI as measured by the Ouchterlony method did not develop. Laboratory and physical signs of possible hepatitis virus contamination were not observed. The long-term replacement therapy, therefore, appears to be safe.
Asunto(s)
Proteínas Sanguíneas/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Deficiencia de alfa 1-Antitripsina , Adulto , Anciano , Proteínas Sanguíneas/deficiencia , Ensayos Clínicos como Asunto , Femenino , Humanos , Infusiones Intravenosas , Enfermedades Pulmonares Obstructivas/genética , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Elastasa Pancreática/análisis , FenotipoRESUMEN
Two male patients ages 54 and 58 years had persisting pneumonia with dry cough, dyspnea, weight loss, and fever up to 39 degrees C that did not respond to erythromycin treatment. There was extensive restrictive impairment of ventilation and loss of diffusing capacity for carbon monoxide. Histologic examination of the basal pulmonary infiltrates showed fibrosing alveolitis. Serologic titers indicated that the patients had suffered from Legionella pneumophila infection. We believe that Legionella had caused the fibrosing alveolitis since there was absence of any other causative agents or factors. Both patients responded to corticosteroid treatment with rapid clinical improvement but delayed radiologic regression.
Asunto(s)
Enfermedad de los Legionarios/complicaciones , Prednisona/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , RadiografíaRESUMEN
Activated monocytes secrete tumor necrosis factor-alpha (TNF-alpha), whose inflammatory and fibroblast activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human alveolar macrophages (AM) and peripheral blood mononuclear cells (PBMNC) were exposed to soot particles or asbestos fibres in concentrations ranging from 5-50 micrograms/1 x 10(6) cells for 8 hrs in RPMI medium. A culture was established with the exposed monocytes and the remaining cells were used to determine TNF-alpha. TNF-alpha was quantified by commercial ELISA-kits. 8 hrs exposure to soot particles and asbestos fibres induced a significant increase in spontaneous TNF-alpha release (p < 0.05). Cytotoxicity of monocytes was checked by trypan blue exclusion and lactate dehydrogenase assay, noted values ranging from 0.5%-16.2%.
Asunto(s)
Amianto/toxicidad , Carbono/toxicidad , Macrófagos Alveolares/inmunología , Monocitos/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Líquido del Lavado Bronquioalveolar/citología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/patología , Masculino , Persona de Mediana Edad , Fibras Minerales , Monocitos/efectos de los fármacos , Monocitos/patología , Estadificación de Neoplasias , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In the present study we investigated the influence of two common air pollutants, sulfur dioxide (SO2) and nitrogen dioxide (NO2) on ciliary beat frequency (CBF). Ciliated cells were obtained by nose brush from 12 healthy volunteers and placed on a polycarbonate membrane which was in contact with Ringer's electrolyte solution. This allowed the supply of the cells by capillarity in parallel to the reaction of the pollutants with the cell surfaces. In an exposure chamber the cells were exposed for 30 min. at 37 degrees C either to SO2 (2.5-12.5 ppm) or to NO2 (3.0-15.0 ppm), or to a mixture of NO2 (12.0 ppm) and SO2 (2.5 or 5.0 ppm). CBF was measured by video-interference-microscopy. With SO2 we observed a dose-dependent decrease in CBF with Ringer's solution. 2.5 ppm SO2 caused a 42.8% decrease and 12.5 ppm a decline of approximately 100% (8.10 +/- 0.24 Hz vs. 0.28 +/- 0.20 Hz). In parallel, we observed a decrease in the pH-value from 7.4 to 3.6. 30 min. NO2 exposure (3.0-15.0 ppm) induced a significant dose dependent increase in CBF from 8.4 +/- 0.34 Hz to 9.4 +/- 0.44 Hz. Exposure to a mixture of SO2 and NO2 with Ringer's solution revealed that SO2 exerts a stronger influence on CBF than NO2. Exposure to both pollutants resulted in the same as exposure to SO2 alone. Our findings demonstrate a strong correlation between SO2-modified pH values and CBF. Exposure to a combination of two pollutants revealed the dominant influence of SO2 on CBF while the augmented effect of exposure to NO2 alone might be due to the oxidative potential of this gas.
Asunto(s)
Mucosa Nasal/fisiología , Dióxido de Nitrógeno/farmacología , Dióxido de Azufre/farmacología , Adulto , Cilios/efectos de los fármacos , Cilios/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Mucosa Nasal/citología , Mucosa Nasal/efectos de los fármacosRESUMEN
Alveolar macrophages located on the alveolar surface have contact with air pollutants. We evaluated the dose-dependent effect of nitrogen dioxide exposure on the oxidative metabolism of alveolar macrophages and peripheral blood mononuclear cells by measuring the spontaneous and stimulated reactive oxygen intermediates production. Alveolar macrophages or peripheral blood mononuclear cells were placed on a polycarbonate membrane, which was in direct contact with the surface of a nutrient reservoir. The cells were exposed to nitrogen dioxide during different periods of time, varying between 30 and 120 min at concentrations ranging from 0.1 to 0.5 ppm. Exposure of alveolar macrophages to nitrogen dioxide for 30 min yielded a dose-dependent stimulation of reactive oxygen intermediates generation of 1.7- to 2.9-fold of control. An 120-min exposure to nitrogen dioxide at concentrations between 0.1 and 0.5 ppm resulted in a similar reactive oxygen intermediates production of about 1.9- to 2.2-fold of control at all concentrations tested. The nitrogen dioxide exposure to peripheral blood mononuclear cells yielded identical results. These experiments demonstrate that alveolar macrophages and peripheral blood mononuclear cells become activated by nitrogen dioxide and that concentrations up to 0.5 ppm nitrogen dioxide induce an increase in reactive oxygen intermediates production after 30 to 120 min exposure of the cells.
Asunto(s)
Leucocitos Mononucleares/metabolismo , Macrófagos Alveolares/metabolismo , Dióxido de Nitrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , MasculinoRESUMEN
Tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and transforming growth factor-beta are cytokines synthesized by alveolar macrophages. We investigated the effect of sulfur dioxide, a major air pollutant, on the production of these cytokines by alveolar macrophages. The cells were layered on a polycarbonate membrane and exposed for 30 min to 0.0, 1.0, 2.5, and 5.0 ppm sulfur dioxide at 37 degrees C and 100% air humidity. The cells were incubated for 24 h after exposure, thus allowing cytokine release. Cytotoxic effects of sulfur dioxide were evaluated by trypan blue exclusion. Cytokines were measured with enzyme-linked immunosorbent assays (i.e., tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) or by use of a specific bioassay (i.e., transforming growth factor-beta). The toxicity of sulfur dioxide for alveolar macrophages ranged from 3.1 % to 9.5 %. A 30-min exposure to sulfur dioxide induced a significant decrease in spontaneous and lipopolysaccharide-stimulated tumor necrosis factor-alpha (p < .001) and lipopolysaccharide-stimulated interleukin-1beta release (p < .05). The release of interleukin-6 and transforming growth factor-beta was not affected significantly by sulfur dioxide exposure. Our results demonstrated a functional impairment of alveolar macrophages after sulfur dioxide exposure (i.e., release of tumor necrosis factor-alpha and interleukin-1beta). Neither spontaneous nor stimulated release of interleukin-6 and transforming growth factors were influenced by exposure to sulfur dioxide.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Interleucinas/biosíntesis , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Dióxido de Azufre/efectos adversos , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucinas/análisis , Masculino , Persona de Mediana Edad , Factor de Crecimiento Transformador beta/análisis , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Mucociliary transport is an important defense mechanism of the respiratory tract. The aim of this study was to investigate the effect of SO2 and NO2 at different concentrations on ciliary beat frequency (ZSF). Single ciliated cells were obtained from 25 volunteers by nose brush. ZSF was quantified using video-interference-microscopy. The cells were placed on a polycarbonate membrane, which was in contact with the surface of a reservoir filled with RPMI medium (bicarbonate buffered) or electrolyte solution (Ringer), allowing the cells to be supplied by capillarity. In an exposure chamber the cells were exposed for 30 to 120 min to SO2 2.5 to 15.0 ppm at 37 degrees C. SO2 induced a dose dependent decrease in ZSF of the cells, supported by Ringer solution. 2.5 ppm SO2 caused a 42.8%, 12.5 ppm a nearly 100% decrease (8.10 +/- 0.24 vs. 0.28 +/- 0.20 Hz). ZSF of cells cultured in RPMI medium was reduced moderately after 12.5 ppm SO2 exposure (7.90 +/- 0.26 vs. 6.66 +/- 0.31 Hz). In Ringer solution we observed a decrease of pH after 30 min SO2 exposure with 12.5 ppm to a minimum value of 3.6. In marked contrast, the pH of RPMI medium remained constant at 7.5 under identical conditions. After adding RPMI medium to Ringer solution, ZSF increased in parallel to the pH (5.0 ppm: 2.77 +/- 0.37 to 7.97 +/- 0.49 Hz). After an initial increase in ZSF, 120 min NO2 exposure to 15.0 ppm yielded a decrease in ZSF of 23.3% under conditions of constant pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Depuración Mucociliar/efectos de los fármacos , Dióxido de Nitrógeno/toxicidad , Dióxido de Azufre/toxicidad , Adulto , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Mucosa Nasal/efectos de los fármacosRESUMEN
Treatment and prognosis of tuberculosis. Worldwide the so-called short-course chemotherapy has become the standard treatment for tuberculosis. The 6-month regimen consists of isoniazid, rifampin, and pyrazinamid given for 2 month followed by isoniazid and rifampin for 4 month. Ethambutol or streptomycin is added in the first 2 month in patients with advanced disease. This recommendation applies to both HIV-infected and uninfected persons. The major determinant of the outcome of treatment is patient adherence to the drug regimen. In susceptible strains the success rate with the 6-month regimen in sputum conversion is far beyond 90% within the first two month of therapy. The relapse rate after 3 to 5 years is about 0-3%. Multiple-drug-resistant tuberculosis (i.e., resistance to at least two drugs) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. For patients with tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. The role of new agents such as the quinolone derivatives and amikacin in the treatment of multidrug-resistant disease is not known, although these drugs are commonly being used in such cases.
Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Antituberculosos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoAsunto(s)
Neumotórax/terapia , Drenaje , Humanos , Métodos , Neumotórax/complicaciones , Neumotórax/etiologíaAsunto(s)
Bronquitis , Adolescente , Adulto , Aerosoles/uso terapéutico , Anciano , Obstrucción de las Vías Aéreas/tratamiento farmacológico , Ampicilina/uso terapéutico , Espasmo Bronquial/prevención & control , Bronquitis/complicaciones , Bronquitis/diagnóstico , Bronquitis/tratamiento farmacológico , Bronquitis/etiología , Bronquitis/genética , Cloranfenicol/uso terapéutico , Enfermedad Crónica , Tos/etiología , ADN/análisis , Expectorantes/uso terapéutico , Glicosaminoglicanos/análisis , Humanos , Inmunoglobulina G/análisis , L-Lactato Deshidrogenasa/análisis , Persona de Mediana Edad , Muramidasa/análisis , Yoduro de Potasio/uso terapéutico , Pruebas de Función Respiratoria , Esputo/microbiologíaAsunto(s)
Antibacterianos/uso terapéutico , Bronquitis/tratamiento farmacológico , Ampicilina/farmacología , Ampicilina/uso terapéutico , Antibacterianos/clasificación , Enfermedad Crónica , Combinación de Medicamentos , Haemophilus influenzae/efectos de los fármacos , Humanos , Penicilinas/uso terapéutico , Streptococcus pneumoniae/efectos de los fármacos , Sulfonamidas/uso terapéutico , Trimetoprim/uso terapéuticoAsunto(s)
Insuficiencia Respiratoria/tratamiento farmacológico , Espironolactona/uso terapéutico , Adulto , Anciano , Bicarbonatos/sangre , Dióxido de Carbono/sangre , Humanos , Concentración de Iones de Hidrógeno , Hipoventilación/sangre , Hipoventilación/tratamiento farmacológico , Inyecciones Intravenosas , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Potasio/sangre , Insuficiencia Respiratoria/sangre , Sodio/sangre , Espironolactona/farmacologíaRESUMEN
Diseases of autoaggression can be produced if immunotolerance to endogenous tissue is lost. Such diseases become manifest in the pulmonary and pleura regions mainly within the framework of systemic diseases of the connective tissue (collagenoses) and of the vessels (angiitides). Lupus erythematodes disseminatus belongs to the first group which also includes rheumatoid arthritis, sclerodermia, and dermatomyositis, whereas panarteritis nodosa belongs to the second group, which comprises among others arteritis of the arteria pulmonalis, Wegener's granulomatosis, Goodpasture's syndrome and Ceelen's disease. Pleuropulmonary involvement is frequent in these systemic diseases; it is in fact the principal sign in Goodpasture's syndrome and in Ceelen's disease.